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Skin wound healing is a complex process involving various cellular and molecular events. However, chronic wounds, particularly in individuals with diabetes, often experience delayed wound healing, potentially leading to diabetic skin complications. In this study, we examined the effects of umbelliferone on skin wound healing using dermal fibroblasts and skin tissues from a type 2 diabetic mouse model. Our results demonstrate that umbelliferone enhances several crucial aspects of wound healing. It increases the synthesis of key extracellular matrix components such as collagen I and fibronectin, as well as proteins involved in cell migration like EVL and Fascin-1. Additionally, umbelliferone boosts the secretion of angiogenesis factors VEGF and HIF-1α, enhances the expression of cell adhesion proteins including E-cadherin, ZO-1, and Occludin, and elevates levels of skin hydration-related proteins like HAS2 and AQP3. Notably, umbelliferone reduces the expression of HYAL, thereby potentially decreasing tissue permeability. As a result, it promotes extracellular matrix deposition, activates cell migration and proliferation, and stimulates pro-angiogenic factors while maintaining skin barrier functions. In summary, these findings underscore the therapeutic potential of umbelliferone in diabetic wound care, suggesting its promise as a treatment for diabetic skin complications. Key messages: Umbelliferone suppressed the breakdown of extracellular matrix components in the skin dermis while promoting their synthesis. Umbelliferone augmented the migratory and proliferative capacities of fibroblasts. Umbelliferone activated the release of angiogenic factors in diabetic wounds, leading to accelerated wound healing. Umbelliferone bolstered intercellular adhesion and reinforced the skin barrier by preventing moisture loss and preserving skin hydration. Summary of the protective impact of umbelliferone against delayed wound healing and skin barrier impairment in diabetic dermal fibroblasts and skin tissues. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Existing methods to evaluate skin care products suffer limitations. This is the case for ex vivo skin explants, a first‐choice 3D model. While essential to analyse mid‐ to long‐term biological effects, this classical model hinders assessing microrelief variations. To circumvent these limitations, we developed an ex vivo PERFused EXplant setup (Perfex) that maintains the outer skin surface in the open air, closely mirroring physiological conditions.A custom‐designed reservoir enables perfusing the dermal side of explants with buffered, temperature‐controlled medium, while the epidermis is subjected to “normal” conditions. Skin tension and characteristics of the stratum corneum, microrelief, histology and immunohistology (collagen types I and III, elastin and fibrillin‐1) were analysed and compared to those of explants maintained under conventional conditions or in vivo skin. The effects of skin care formulas intended to induce short‐ and/or mid‐ to long‐term effects were also assessed.Skin explants maintained with the Perfex setup exhibit characteristics (firmness, elasticity, hydration and barrier function) closer to those of in vivo skin than with conventional conditions. Moreover, Perfex‐maintained explants present no alteration in histology after 7 days and slight variation in the expression of key protein markers. Microrelief characteristics also remain mostly stable over 7 days. Formula applications corroborate that skin tensor‐containing products primarily induce short‐term changes in the microrelief, while those with biologically active ingredients mainly lead to mid‐ to long‐term effects on the histology and expression of molecular markers. Furthermore, maintaining skin explants with a physiologically relevant skin surface enabled analysing the relationship between microrelief and key markers, showing that fibrillin‐1 is the protein most correlated with microrelief characteristics.The Perfex setup allows for similar preservation of skin explant histology and key protein expression as the conventional system, yet it maintains a skin surface close to that of in vivo skin. Therefore, it is valuable to analyse both the short‐ and mid‐ to long‐term impacts of skin care formulas and better comprehend their effects. The Perfex system also offers a new tool for investigating fundamental questions, such as the link that can exist between dermal proteins and skin surface properties. [ABSTRACT FROM AUTHOR]

Owing to its tyrosinase inhibitory activity, α-arbutin has been added to several skin care products as a skin-lightening agent. However, the protective effect of α-arbutin against ultraviolet A (UVA)-induced photoaging has not been well investigated. The present study was designed to investigate the photoprotective effect and mechanism of α-arbutin against UVA-induced photoaging. In vitro experiments, HaCaT cells were treated with UVA at a dose of 3 J/cm2 to evaluate the anti-photoaging effect of α-arbutin. α-Arbutin was found to exhibit a strong antioxidant effect by increasing glutathione (GSH) level and inhibiting reactive oxygen species (ROS) production. Meanwhile, α-arbutin markedly improved the expression of sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) proteins, initiating downstream signaling to increase mitochondrial membrane potential and mediate mitochondrial biogenesis, and improve mitochondrial structure significantly. In vivo analysis, the mice with shaved back hair were irradiated with a cumulative UVA dose of 10 J/cm2 and a cumulative ultraviolet B (UVB) dose of 0.63 J/cm2. The animal experiments demonstrated that α-arbutin increased the expression of SIRT3 and PGC-1α proteins in the back skin of mice, thereby reducing UV-induced skin damage. In conclusion, α-arbutin protects HaCaT cells and mice from UVA damage by regulating SIRT3/PGC-1α signaling pathway. [ABSTRACT FROM AUTHOR]

The skin is covered by a protective mucus layer, which is essential to the innate defense mechanism of fish. Investigating the response of skin mucus to various toxic stresses is crucial for enhancing its ability to tackle environmental challenges and developing strategies to mitigate toxic effects. Alkalinity stress assays (50 mmol/L NaHCO3) were conducted on crucian carp (Carassius auratus) from Lake Dali Nur (pH = 9.6) and Ping Xiang red crucian carp from freshwater (pH = 7) over 7 days. The expression of skin mucous proteins was analyzed using the liquid chromatography (LC)-spectrometry (MS)/MS Analysis-Data-independent acquisition (DIA) mode. A total of 12,537 proteins were identified across 20 samples from four groups, with 12,025 quantified. In the alkaline water population, high alkali stress resulted in the up-regulation of 139 proteins and the down-regulation of 500 proteins. In contrast, the freshwater population showed an increase in 112 proteins and a decrease in 120; both populations had a total of 23 genes up-regulated and 21 down-regulated. The protein regulatory network for the alkaline water group included 3146 pairwise interactions among 464 nodes, with only 20 being differentially expressed proteins. Conversely, the freshwater group's network comprised just 1027 specific interactions across 337 nodes, with 6 corresponding to differentially expressed proteins. A common protein regulatory network responding to high alkali stress was extracted and visualized for both populations. Based on their regulatory relationships and expression levels, these proteins are hypothesized to play similar roles under high alkali stress. Notably, the alpha-globin fragment and keratin type I cytoskeletal 13-like proteins showed markedly up-regulated expression, with the alpha-globin fragment increasing nearly a thousandfold from an extremely low level. This suggests it could serve as a potential biomarker for alkali tolerance, warranting further investigation. [ABSTRACT FROM AUTHOR]

The contents and distribution of different collagen types in bones, skins, and guts of salmon and cod were assessed by chemical and mass spectroscopic methods. The highest levels of collagen were found in the skin (89–98%), followed by the bones (79–89%), and the guts (25–36%). A variety of different collagen α-chain proteins were detected in the assessed tissues, with proteins from 12 to 6 different collagen types quantified in salmon and cod, respectively. The less well-known collagen IV was found in significant levels in all tissues, and the most diverse collagen composition was found in the bones. [ABSTRACT FROM AUTHOR]

Background Sex hormone changes during menopausal transition contribute to declining skin health. However, how menopause and its treatment by hormone replacement therapy (HRT) impact the skin barrier and immune system is unclear. Objectives To examine how menopause and HRT affect the skin barrier and immune cell composition in postmenopausal women following irritant challenge. Methods Two cohorts of postmenopausal women were recruited to the study. The first cohort consisted of 10 untreated women [HRT–; mean (SEM) age 56.5 (1.6) years (range 48–63)] and the second was composed of 8 women receiving HRT [HRT+; mean (SEM) age 54.0 (2.1) years (range 48–63)]. Skin irritation was induced by applying topical sodium lauryl sulfate (SLS) 1.25% to occluded buttock skin for 48 h. Clinical assessment was conducted after 24 h, followed by biopsy of both SLS-challenged and unchallenged skin for analysis of skin barrier proteins and immune cell distribution using immunofluorescence. Results Clinically, there were no significant differences in skin irritant responses between those taking or not taking HRT (including increased skin redness and blood flow). In response to SLS challenge a significant increase in transepidermal water loss (P < 0.05), filaggrin deposition and cytokeratin 10 (K10)+ cell layers (P < 0.01) was observed in individuals receiving HRT compared with the HRT– group. Following SLS challenge in individuals taking HRT, a significant (P < 0.01) reduction in CD207+ cells in the epidermis was observed, accompanied by an increase of CD207+ cells in the dermis, indicative of migrating Langerhans cells (LCs). Significantly fewer migrating LCs were found in those who were not receiving HRT (P < 0.01). Furthermore, the numbers of dermal dendritic cells (DCs), macrophages, and CD11c+CD206– and CD68+CD206– subsets were found to be significantly (P < 0.05) higher in those taking HRT following SLS challenge. Conclusions Individuals receiving HRT displayed enhanced skin barrier response to SLS challenge with thicker filaggrin and increased K10+ epidermal cell layers. Following challenge, HRT users exhibited elevated LC, inflammatory DC and macrophage counts in the dermis. These may render skin both more prone to inflammation and more capable of resolving it, while also promoting skin repair. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases. Topical treatments are recommended for all patients regardless of severity, making it essential to develop an effective topical AD treatment with minimal side effects; We investigated the efficacy of topical application of naringin in AD and explored the possible mechanisms using an AD mouse model induced by 1-chloro-2,4-dinitrobenzene (DNCB). Clinical, histological, and immunological changes related to AD and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling proteins in the skin tissues were measured as outcomes; Naringin treatment resulted in a significant improvement in dermatitis severity score and reduced epidermal thickness and mast cell count in the skin (p < 0.05). Naringin also demonstrated the ability to inhibit DNCB-induced changes in interleukin (IL) 4, chemokine (C-C motif) ligand (CCL) 17, CCL22, IL1β, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) levels by quantitative real-time polymerase chain reaction (qRT-PCR) and IL13 by enzyme-linked immunosorbent assay (ELISA) (p < 0.05). Western blot results exhibited the decreased JAK1, JAK2, STAT1, STAT3, phospho-STAT3, and STAT6 expression in the naringin-treated groups (p < 0.05); The findings of this study suggest that topical naringin may effectively improve the symptoms of AD and could be used as a therapeutic agent for AD. [ABSTRACT FROM AUTHOR]

During the key event 1 of skin sensitization defined as covalent binding or haptenization of sensitizer to either thiol or amino group of skin proteins, a sensitizer not only covalently binds with skin proteins but also interacts with nucleophilic small molecules such as glutathione (GSH). Although GSH would not be directly associated with skin sensitization, this interaction may be applied for developing an alternative test method simulating key event 1, haptenization. Thus, the aim of the present study was to examine whether N-acetyl-L-cysteine methyl ester (NACME), a thiol-containing compound, was selected as an electron donor to determine whether NACME reacted with sensitizers. Following a reaction of NACME with a sensitizer in a 96-well plate, the remaining NACME was measured spectrophotometrically using 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB). Following the optimization of test conditions with two different vehicles, such as acetonitrile (ACN) and dimethyl sulfoxide (DMSO), 64 test chemicals were tested to determine the predictive capacity of current NACME test method. The results obtained showed, the predictive capacity of 94.6% sensitivity, 88.9% specificity, and 92.2% accuracy utilizing DMSO as a vehicle with a cutoff NACME depletion of 5.85%. The three parameters were also over 85% in case of ACN. These values were comparable to or better than other OECD-approved test methods. Data demonstrated that a simple thiol-containing compound NACME might constitute as a reliable candidate for identifying reactive skin sensitizers, and that this method be considered as practical method as a screening tool for assessing a chemical's tendency to initiate skin sensitization. [ABSTRACT FROM AUTHOR]

Owing to its tyrosinase inhibitory activity, α-arbutin has been added to several skin care products as a skin-lightening agent. However, the protective effect of α-arbutin against ultraviolet A (UVA)-induced photoaging has not been well investigated. The present study was designed to investigate the photoprotective effect and mechanism of α-arbutin against UVA-induced photoaging. In vitro experiments, HaCaT cells were treated with UVA at a dose of 3 J/cm2 to evaluate the anti-photoaging effect of α-arbutin. α-Arbutin was found to exhibit a strong antioxidant effect by increasing glutathione (GSH) level and inhibiting reactive oxygen species (ROS) production. Meanwhile, α-arbutin markedly improved the expression of sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) proteins, initiating downstream signaling to increase mitochondrial membrane potential and mediate mitochondrial biogenesis, and improve mitochondrial structure significantly. In vivo analysis, the mice with shaved back hair were irradiated with a cumulative UVA dose of 10 J/cm2 and a cumulative ultraviolet B (UVB) dose of 0.63 J/cm2. The animal experiments demonstrated that α-arbutin increased the expression of SIRT3 and PGC-1α proteins in the back skin of mice, thereby reducing UV-induced skin damage. In conclusion, α-arbutin protects HaCaT cells and mice from UVA damage by regulating SIRT3/PGC-1α signaling pathway. [ABSTRACT FROM AUTHOR]

CRTC1::TRIM11 cutaneous tumor (CTCT) is a rare skin tumor of uncertain differentiation. In the 49 reported cases, only four cases showed regional or distant metastasis, but follow‐up remains limited. Herein, we present a case of metastatic CTCT with ulceration, a histological feature that has not been previously described. A 75‐year‐old male with a 2‐month history of toe ulceration underwent a shave biopsy, which showed a dermal nodular neoplasm that was immunoreactive for SOX10 and S100, negative for Melan‐A, and was initially diagnosed as melanoma. Upon pathology review at our institution, the tumor was composed of intersecting fascicles and nests of epithelioid and spindle cells. Additional immunohistochemistry revealed immunoreactivity of the tumor for MiTF and NTRK and negativity for HMB‐45 and PRAME. Next‐generation sequencing identified CRTC1::TRIM11 fusion, leading to a revised diagnosis of CTCT. The patient proceeded to a toe amputation and sentinel lymph node (SLN) biopsy 5 months after the shave biopsy. The amputation showed residual CTCT and a focus on lymphovascular invasion. The SLN revealed multifocal subcapsular metastases. The patient was started on adjuvant nivolumab and showed biopsy‐proven recurrence in the right inguinal lymph nodes and imaging findings suspicious for pulmonary metastases 8 months after the excision. In summary, we present a case of CTCT with ulceration and lymphovascular invasion. We also provide additional evidence that a subset of CTCT behaves aggressively. The optimal surgical and medical treatments are unknown. [ABSTRACT FROM AUTHOR]

Protein therapeutics are emerging as essential technologies due to their functional and chemical properties. However, their application is currently limited to delivery by oral and injection methods—the former being inefficient and the latter invasive and potentially tissue damaging. Researchers are, therefore, exploring noninvasive delivery systems for proteins through the skin, including transdermal and topical delivery. The large molecular size of proteins presents a key challenge for skin penetration, hindering their ability to penetrate the dense skin lamellar structure. This review focuses on using nanoparticles as carriers to increase protein stability and enhance skin penetration. The use of noninvasive or minimally invasive enhancers for controlling and improving penetration depth is also examined. Furthermore, the physical properties of nanoparticles that affect delivery are evaluated, aiming to propose ways to advance transdermal and topical delivery methods in the future. [ABSTRACT FROM AUTHOR]

Background Recessive dystrophic epidermolysis bullosa (RDEB) is a blistering disease caused by mutations in the gene encoding type VII collagen (C7). RDEB is associated with fibrosis, which is responsible for severe complications. The phenotypic variability observed in siblings with RDEB suggests that epigenetic modifications contribute to disease severity. Identifying epigenetic changes may help to uncover molecular mechanisms underlying RDEB pathogenesis and new therapeutic targets. Objectives To investigate histone acetylation in RDEB skin and to explore histone deacetylase inhibitors (HDACi) as therapeutic molecules capable of counteracting fibrosis and disease progression in RDEB mice. Methods Acetylated histone levels were detected in human skin by immunofluorescence and in RDEB fibroblasts by enzyme-linked immunosorbent assay (ELISA). The effects of givinostat and valproic acid (VPA) on RDEB fibroblast fibrotic behaviour were assessed by a collagen–gel contraction assay, Western blot and immunocytofluorescence for α-smooth muscle actin, and ELISA for released transforming growth factor (TGF)-β1. RNA sequencing was performed in HDACi- and vehicle-treated RDEB fibroblasts. VPA was systemically administered to RDEB mice and effects on overt phenotype were monitored. Fibrosis was investigated in the skin using histological and immunofluorescence analyses. Eye and tongue defects were examined microscopically. Mass spectrometry proteomics was performed on skin protein extracts from VPA-treated RDEB and control mice. Results Histone acetylation decreases in RDEB skin and primary fibroblasts. RDEB fibroblasts treated with HDACi lowered fibrotic traits, including contractility, TGF-β1 release and proliferation. VPA administration to RDEB mice mitigated severe manifestations affecting the eyes and paws. These effects were associated with fibrosis inhibition. Proteomic analysis of mouse skin revealed that VPA almost normalized protein sets involved in protein synthesis and immune response, processes linked to the increased susceptibility to cancer and bacterial infections seen in people with RDEB. Conclusions Dysregulated histone acetylation contributes to RDEB pathogenesis by facilitating the progression of fibrosis. Repurposing of HDACi could be considered for disease-modifying treatments in RDEB. [ABSTRACT FROM AUTHOR]

[Display omitted] The skin has a multilayered structure, and deep-seated injuries are exposed to external microbial invasion and in vivo microenvironmental destabilization. Here, a bilayer bionic skin scaffold (Bilayer SF) was developed based on methacrylated sericin protein to mimic the skin's multilayered structure and corresponding functions. The outer layer (SF@TA), which mimics the epidermal layer, was endowed with the function of resisting external bacterial and microbial invasion using a small pore structure and bio-crosslinking with tannic acid (TA). The inner layer (SF@DA@Gel), which mimics the dermal layer, was used to promote cellular growth using a large pore structure and introducing dopamine (DA) to regulate the wound microenvironment. This Bilayer SF showed good mechanical properties and structural stability, satisfactory antioxidant and promote cell proliferation and migration abilities. In vitro studies confirmed the antimicrobial properties of the outer layer and the pro-angiogenic ability of the inner layer. In vivo animal studies demonstrated that the bilayer scaffolds promoted collagen deposition, neovascularization, and marginal hair follicle formation, which might be a promising new bionic skin scaffold. [ABSTRACT FROM AUTHOR]

Chios mastic gum (CMG), the resin of Pistacia lentiscus var. Chia, is a product with great ethnopharmacological and economic significance. This study attempts to investigate, for the first time, the activity of CMG, its fractions and isolated compounds against specific enzymes, which play pivotal roles in the degradation of proteins contained in skin connective tissue. Initially, crude CMG was subjected to extraction, fractionation and isolation through different chromatographic techniques to obtain the acidic and neutral fraction of terpenes. Additionally, the characteristic and major active triterpene acids of CMG, masticadienonic and isomasticadienonic acids (MNA, IMNA) were isolated in pure form. All samples were analysed by means of High-Performance Thin-Layer Chromatography (HPTLC) with four distinct development systems to obtain their constituents' profile. Finally, samples were tested for their ability to inhibit the elastase and collagenase enzymes. According to our findings, for collagenase, a mixture of MNA and IMNA demonstrated the most potent activity with an IC50 value of 31.07 μg/mL, while for elastase CMG's acidic fraction provided the most promising results with an IC50 value of 17.30 μg/mL. Overall, these results attempt to fill the gap in scientific knowledge about the use of CMG and its constituents in skincare and cosmetic products. [ABSTRACT FROM AUTHOR]

The common octopus (Octopus vulgaris) is an excellent candidate for aquaculture diversification, due to its biological traits and high market demand. To ensure a high-quality product while maintaining welfare in captive environments, it is crucial to develop non-invasive methods for testing health biomarkers. Proteins found in skin mucus offer a non-invasive approach to monitoring octopus welfare. This study compares the protein profiles in the skin mucus of wild, aquarium-maintained, and senescent specimens to identify welfare biomarkers. A tandem mass tag (TMT) coupled with an Orbitrap Eclipse Tribrid mass spectrometer was used to create a reference dataset from octopus skin mucus, identifying 1496 non-redundant protein groups. Although similar profiles were observed, differences in relative abundances led to the identification of potential biomarkers, including caspase-3-like, protocadherin 4, deleted in malignant brain tumors, thioredoxin, papilin, annexin, cofilin and mucin-4 proteins. Some of these proteins also revealed potential as bioactive peptides. This investigation provides the most extensive analysis of the skin mucus proteome in the common octopus and is the first to explore how aquarium maintenance and senescence alter the mucus proteome. This research highlights the potential of skin mucus protein/peptides as non-invasive monitoring biomarkers in cultured animals. [ABSTRACT FROM AUTHOR]

Background: Foxn1−/− deficient mice are a rare model of regenerative skin wound healing among mammals. In wounded skin, the transcription factor Foxn1 interacting with hypoxia-regulated factors affects re-epithelialization, epithelial-mesenchymal transition (EMT) and dermal white adipose tissue (dWAT) reestablishment and is thus a factor regulating scar-forming/reparative healing. Here, we hypothesized that transcriptional crosstalk between Foxn1 and Hif-1α controls the switch from scarless (regenerative) to scar-present (reparative) skin wound healing. To verify this hypothesis, we examined (i) the effect of hypoxia/normoxia and Foxn1 signalling on the proteomic signature of Foxn1−/− (regenerative) dermal fibroblasts (DFs) and then (ii) explored the effect of Hif-1α or Foxn1/Hif-1α introduced by a lentiviral (LV) delivery vector to injured skin of regenerative Foxn1−/− mice with particular attention to the remodelling phase of healing. Results: We showed that hypoxic conditions and Foxn1 stimulation modified the proteome of Foxn1−/− DFs. Hypoxic conditions upregulated DF protein profiles, particularly those related to extracellular matrix (ECM) composition: plasminogen activator inhibitor-1 (Pai-1), Sdc4, Plod2, Plod1, Lox, Loxl2, Itga2, Vldlr, Ftl1, Vegfa, Hmox1, Fth1, and F3. We found that Pai-1 was stimulated by hypoxic conditions in regenerative Foxn1−/− DFs but was released by DFs to the culture media exclusively upon hypoxia and Foxn1 stimulation. We also found higher levels of Pai-1 protein in DFs isolated from Foxn1+/+ mice (reparative/scar-forming) than in DFs isolated from Foxn1−/− (regenerative/scarless) mice and triggered by injury increase in Foxn1 and Pai-1 protein in the skin of mice with active Foxn1 (Foxn1+/+ mice). Then, we demonstrated that the introduction of Foxn1 and Hif-1α via lentiviral injection into the wounded skin of regenerative Foxn1−/− mice activates reparative/scar-forming healing by increasing the wounded skin area and decreasing hyaluronic acid deposition and the collagen type III to I ratio. We also identified a stimulatory effect of LV-Foxn1 + LV-Hif-1α injection in the wounded skin of Foxn1−/− mice on Pai-1 protein levels. Conclusions: The present data highlight the effect of hypoxia and Foxn1 on the protein profile and functionality of regenerative Foxn1−/− DFs and demonstrate that the introduction of Foxn1 and Hif-1α into the wounded skin of regenerative Foxn1−/− mice activates reparative/scar-forming healing. [ABSTRACT FROM AUTHOR]

Time-of-death extrapolation has always been one of the most important issues in forensic practice. For a complicated case in which a corpse is destroyed with little evidence, judging the time of death of the deceased is a major challenge, which also enables criminals to escape legal sanctions. To find a method to roughly judge the time of death of a corpse with only a small amount of skin tissue, in this study, we established an early death model by using mice; furthermore, the postmortem interval was estimated by determining the protein and mRNA levels of Bax and Bcl-2 in the skin. In this process, 0 h after death was used as the control group, and the expression levels of Bax and Caspase-3 reached the maximum value at 8–12 h, while Bcl-2, as an inhibitor of apoptosis protein, peaked after 24 h. The mRNA expression levels of related proteins in postmortem skin tissues were also different. The results of these data indicate that the protein and mRNA levels of Bax and Bcl-2 in the skin have potential application in early time-of-death estimation. [ABSTRACT FROM AUTHOR]

To investigate the effects of water flow on fish body color, the number of melanophore and gene expression in zebrafish skin were investigated under water flow culture with two different flow rates 0. 010 m/s (low flow rate) and 0. 022 m/s (high flow rate). The results showed that compared with low flow rate, the number of skin melanophore increased significantly after 3 months of culturing zebrafish under higher flow rate, especially in the caudal region of the body of the fish, the expression levels of the skin melanophore marker genes kita, mitfa and tyrp1a were significantly increased as well. Meanwhile, the relative expression level of the xanthophore marker gene csf1ra was significantly decreased, and there was no significant change in the iridophore marker gene pnp4a, indicating that the high flow rate water induced the formation of melanophore and inhibited the formation of xanthophore. The RT-qPCR results showed that the expression of melanophore formation inhibitor gene asip1 was significantly decreased in the skin of zebrafish in the high-flow group compared with that in the low-flow group; the melanocortin receptor gene mc1r and the amelanocortinogen gene pomca, which are related to melanophore formation, were not significantly changed; and the retinoid dehydrogenase genes raldh2 and raldh3, which are related to retinoic acid synthesis, were significantly downregulated; water flow stimulation upregulated the transient receptor channel protein gene trpv4 and the piezoelectric mechanosensitive channel protein gene piezo2, whereas there was no significant change in piezo1. The above results indicate that the high flow rate water flow induces melanophore formation in zebrafish, possibly as a result of reduced asip1 expression mediated by water flow stimulation through the skin mechanosensitive proteins Trpv4 and Piezo2. Asip1 regulates fat accumulation in addition to melanophore formation, and indeed zebrafish body fullness reduces significantly in the high water flow group compared with low flow rate group. GO enrichment analysiss showed differentially expressed genes was mainly enriched to entries for triglyceride catabolism, HDL particles, lipid binding, etc and differentially expressed genes was significantly enriched in the following KEGG pathways: aminoglycan and nucleotide sugar metabolism, PPAR signaling pathway, linoleic acid metabolism, and arachidonic acid metabolism, etc. RT-qPCR showed the fatty acid peroxidase 2 gene fads2, which is associated with lipid metabolism, was significantly up-regulated, and there was no significant difference in the leptin gene lep, indicating that water flow may affect fat degradation through Asip1 affecting Fads2. In conclusion, this study for the first time reported the effect of water flow on fish body color and proposed a preliminary signaling regulatory pathway, which provides a preliminary theoretical basis for understanding the effect of water flow culture on fish body color and fullness. [ABSTRACT FROM AUTHOR]

This review discusses the current research progress in molecular farming technology in the field of skincare, with an emphasis on molecular farming expression strategies. The strategies of transdermal drug delivery and their advantages are also highlighted. The expression of cosmetically relevant fused proteins has become an important way to enhance the efficacy of the proteins. Therefore, we also discuss the feasibility and strategies for expressing fusion proteins in A. thaliana, specifically the fusion of Epidermal growth factor (EGF) to a cell-penetrating peptide (CPP), in which the production can be greatly enhanced via plant expression systems since these systems offer higher biosecurity, flexibility, and expansibility than prokaryotic, animal and mammalian expression systems. While the fusion of EGF to CCP can enhance its transdermal ability, the effects of the fusion protein on skin repair, melasma, whitening, and anti-aging are poorly explored. Beyond this, fusing proteins with transdermal peptides presents multiple possibilities for the development of tissue repair and regeneration therapeutics, as well as cosmetics and beauty products. As certain plant extracts are known to contain proteins beneficial for skin health, the expression of these proteins in plant systems will better maintain their integrity and biological activities, thereby facilitating the development of more effective skincare products. [ABSTRACT FROM AUTHOR]

Skin sensitisation is a critical adverse effect assessed to ensure the safety of compounds and materials exposed to the skin. Alongside the development of new approach methodologies (NAMs), defined approaches (DAs) have been established to promote skin sensitisation potency assessment by adopting and integrating standardised in vitro, in chemico, and in silico methods with specified data analysis procedures to achieve reliable and reproducible predictions. The incorporation of additional NAMs could help increase accessibility and flexibility. Using superior algorithms may help improve the accuracy of hazard and potency assessment and build confidence in the results. Here, we introduce two new DA models, with the aim to build DAs on freely available software and the newly developed kDPRA for covalent binding of a chemical to skin peptides and proteins. The new DA models are built on an existing Bayesian network (BN) modelling approach and expand on it. The new DA models include kDPRA data as one of the in vitro parameters and utilise in silico inputs from open-source QSAR models. Both approaches perform at least on par with the existing BN DA and show 63% and 68% accuracy when predicting four LLNA potency classes, respectively. We demonstrate the value of the Bayesian network's confidence indications for predictions, as they provide a measure for differentiating between highly accurate and reliable predictions (accuracies up to 87%) in contrast to low-reliability predictions associated with inaccurate predictions. [ABSTRACT FROM AUTHOR]

Leukocyte cell-derived chemotaxin 2 (LECT2) is linked to various immune diseases. Previously, we reported that serum LECT2 levels correlate with disease severity in atopic dermatitis (AD) patients. To investigate the role of LECT2 in AD and elucidate its potential mechanisms, we used LECT2 to treat an ADmouse model induced by 1-Chloro-2,4-dinitrobenzene (DNCB) in LECT2 knockout (KO) and wild-type (WT) mice, and an AD cell model using TNF-α/IFN-γ-induced HaCaT cells. Inflammatory factors and barrier proteins were analyzed by histology, immunohistochemistry, RT-qPCR, ELISA, and Western Blot. Activation of the NFkB signaling pathway was evaluated by Western Blot and immunofluorescence. In the ADmouse model, LECT2 treatment increased epidermal and dermal thickness, mast cell infiltration, and downregulated barrier proteins. Inflammatory factors were increased in skin lesions and serum. In the AD cell model, LECT2 decreased barrier protein levels and increased inflammatory factor levels, enhancing NF-κB P65 nuclear translocation. These results indicate that LECT2 exacerbates AD-like responses by dysregulating the NF-κB signaling pathway, highlighting its potential as a therapeutic target for AD management. [ABSTRACT FROM AUTHOR]

Objective To explore the status and influencing factors of latent tuberculosis infection among high school students in Chongqing and to provide technical support for the prevention and control of tuberculosis in schools in Chongqing. Methods Stratified cluster sampling method was used to select the students of the first and second years of high school in Chongqing in 2023, as the study subjects to detect latent tuberculosis infection with recombinant Mycobacterium tuberculosis fusion protein skin test, to collect the information related to latent tuberculosis infection, and to analyse the influencing factors using Logistic regression model. Results A total of 9161 students in the first and second years of high school in Chongqing were included, and 543 latent tuberculosis infections were detected, with a latent tuberculosis infection rate of 5. 93%. Multifactorial logistic regression analysis showed that history of previous tuberculosis (0R: 4, 244, 95%Cf: 2. 239 - 8. 044), history of close contact with tuberculosis (OR:2. 096, 95% CI: 1, 123 -3.914), smoking (OR: &819, 95% Cf: 3. 562 - 13. 053), and staying up late (<92,: 1. 665, 95% CI: 1. 154 - 2. 402) were risk factors for latent tuberculosis infection in students. Conclusion The rate of latent tuberculosis infection among students in the first and second years of high school in Chongqing is low. Not smoking, not staying up late, avoiding close contact with tuberculosis patients, taking good personal protective measures, strengthening physical exercise, and improving immunity can reduce the risk of students being infected with Mycobacterium tuberculosis. [ABSTRACT FROM AUTHOR]

Fish species of the genus Amphiprion (Perciformes: Pomacentridae) seek protection from predators among the tentacles of sea anemones as their natural habitat, where they live essentially unharmed from stinging by the host's nematocysts. The skin mucus of these anemonefish has been suggested as a protective mechanism that prevents the discharge of the nematocysts upon contact. Whereas some anemonefish species seem to produce their own protective mucous coating, others may acquire mucus (or biomolecules within) from the sea anemone during an acclimation period. In controlled experiments, we show that Amphiprion ocellaris acclimated successfully to their natural host anemone species Stichodactyla gigantea, and also to Stichodactyla haddoni, and in some cases Heteractis crispa, neither of which are natural host species. No symbiosis was observed for three other anemone species tested, Entacmaea quadricolor, Macrodactyla doreensis, and Heteractis malu. We explored the skin mucous protein profile from naive and experienced A. ocellaris during their acclimation to natural and unnatural host anemones. We confidently report the presence of metabolic and structural proteins in the skin mucus of all samples, likely involved in immunological defense, molecular transport, stress response, and signal transduction. For those anemonefish that established symbiosis, there was a clear increase in ribosomal‐type proteins. We additionally provide evidence for the presence of anemone proteins only in the skin mucus of individuals that established symbiosis. Our results support previous speculation of the role of skin mucous–associated proteins in anemonefish–anemone symbiosis. Further exploration of these mucosal proteins could reveal the mechanism of anemonefish acclimation to host anemones. [ABSTRACT FROM AUTHOR]

The main component of human skin is a collagen-rich extracellular matrix (ECM), known as the matrisome. The matrisome is essential for maintaining the structural integrity and mechanical properties of the skin. Recently, we reported notable decreases in matrisome proteins in natural aging and photoaging human skin. This study aims to investigate the mRNA expression of the core matrisome proteins in human skin, comparing young versus aged and sun-protected versus sun-exposed skin by quantitative real-time PCR and immunostaining. Our findings reveal a notable decrease in core matrisome transcription in aged skin. The mRNA expression of the core matrisome, such as collagen 1A1 (COL1A1), decorin, and dermatopontin, is significantly reduced in aged skin compared to its young skin. Yet, the majority of collagen mRNA expression levels of aged sun-exposed skin are similar to those found in young sun-exposed skin. This discrepancy is primarily attributable to a substantial decrease in collagen transcription in young sun-exposed skin, suggesting early molecular changes in matrisome transcription due to sun exposure, which preceded the emergence of clinical signs of photoaging. These findings shed light on the mRNA transcript profile of major matrisome proteins and their alterations in naturally aged and photoaged human skin, offering valuable insights into skin matrisome biology. [ABSTRACT FROM AUTHOR]

Peptides, composed of 2–50 amino acids, have gained attention in anti-aging treatments due to their high safety, low irritation, and cost-effective production. This study aimed to evaluate the anti-wrinkle efficacy of Tetrapeptide-68, derived from the skin structural protein Loricrin, on periorbital wrinkles in women aged 30–65 years. A 12-week, double-blind, randomized controlled trial was conducted with 25 participants who applied the Tetrapeptide-68 (100 ppm) O/W formulation around the eyes. Skin physiological parameters were assessed at baseline, 4, 8, and 12 weeks. Participants also completed efficacy and usability questionnaires. Significant improvements in wrinkle reduction were observed with Tetrapeptide-68 cream treatment, as measured by various skin roughness parameters and 3D imaging analysis. Participants reported positive changes in skin texture and moisture levels, with no adverse reactions noted. Tetrapeptide-68 cream demonstrates promising anti-wrinkle effects, highlighting its potential as an effective ingredient in anti-aging skincare formulations. Further studies are recommended to explore its long-term benefits and underlying mechanisms. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced hair loss is a distressing side effect of cancer treatment, and medical interventions are often needed to address this problem. The objectives of this study were to evaluate the bioactivity of goat placenta (GP) extract on both normal and chemotherapy-induced hair cells and to develop PEGylated liposomes (PL) and microspicule (MS) formulations for promoting hair growth in patients with chemotherapy-induced hair loss. The bioactivities of GP extract on human follicle dermal papilla (HFDP) cells and cells damaged by chemotherapy were assessed. GP extract was incorporated into PLs and MS gel (PL-MS) and then investigated in vitro skin permeation and in vivo studies on the scalps of patients with chemotherapy-induced hair loss. GP extract stimulated HFDP cell proliferation in both normal and cisplatin-damaged cells. PL nanovesicles and MS gel worked synergistically to deliver macromolecular proteins into the skin and hair follicles. The application of GP extract-loaded PL-MS to the scalps of chemotherapy-treated patients for 12 weeks significantly enhanced the hair growth rate, without causing skin irritation. In conclusion, GP extract promoted the proliferation of hair cells damaged by chemotherapy, when this extract, combined with PL-MS, effectively delivered bioactive macromolecules across the skin and hair follicles, resulting in successful regrowth of hair post-chemotherapy. [ABSTRACT FROM AUTHOR]

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

Bovine serum albumin (BSA) hydrogels are non-immunogenic, low-cost, biocompatible, and biodegradable. In order to avoid toxic cross-linking agents, gellan was oxidized with NaIO4 to obtain new functional groups like dialdehydes for protein-based hydrogel cross-linking. The formed dialdehyde groups were highlighted with FT-IR and NMR spectroscopy. This paper aims to investigate hydrogel films for biomedical applications obtained by cross-linking BSA with oxidized gellan (OxG) containing immobilized β-cyclodextrin–curcumin inclusion complex (β-CD–Curc) The β-CD–Curc improved the bioavailability and solubility of Curc and was prepared at a molar ratio of 2:1. The film's structure and morphology were evaluated using FT-IR spectroscopy and SEM. The swelling degree (Q%) values of hydrogel films depend on hydrophilicity and pH, with higher values at pH = 7.4. Additionally, the conversion index of -NH2 groups into Schiff bases increases with an increase in OxG amount. The polymeric matrix provides protection for Curc, is non-cytotoxic, and enhances antioxidant activity. At pH = 5.5, the skin permeability and release efficiency of encapsulated curcumin were higher than at pH = 7.4 because of the interaction of free aldehyde and carboxylic groups from hydrogels with amine groups from proteins present in the skin membrane, resulting in a better film adhesion and more efficient curcumin release. [ABSTRACT FROM AUTHOR]

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

BACKGROUND: The clinical manifestation of acute radiation skin injury is recurrent necrotic ulcers, and its pathogenesis is still not fully understood. The establishment of a suitable animal model will have important clinical implications for the study of its pathogenesis, prevention and treatment. OBJECTIVE: To establish a model of acute β-ray radiation skin injury and to investigate the mechanism of injury. METHODS: Sixty-nine Sprague-Dawley rats were randomly divided into 30, 45, 60 Gy 32P-β-ray groups (n=21 per group) and control group (n=6). A single local irradiation of the back of the rats was performed using 32P radionuclide. The control group was operated in the same way as the irradiated groups except that it was not irradiated. The body mass and skin appearance of the rats were measured at 7, 15, 30, 45, and 60 days after irradiation. Three rats from each group were selected at each observation time point. The skin injury was observed by hematoxylin-eosin staining, Masson staining, transmission electron microscopy, and TUNEL assay. P53, Bcl-2 and Bax protein levels in the skin were measured by immunohistochemistry and western blot assay. RESULTS AND CONCLUSION: There was no accidental death after irradiation, and the body mass of rats showed a gradual increase. The rats showed different degrees of epidermal necrosis, inflammatory cell infiltration, reduction of hair follicles and appendages, and collagen fibrillation, which were evident at 60 and 45 Gy. The levels of serum inflammatory factors, interleukin-6 and tumor necrosis factor-α, were significantly increased in a dose-dependent manner. Under the electron microscope, there are varying degrees of mitochondrial reduction, vacuolization and nuclear pyknosis in the cells. The degree of cell apoptosis showed a certain dose-dependence. Immunohistochemistry and western blot results showed an increase in the expression of P53 and Bax proteins and a decrease in the expression of Bcl-2 protein in the skin after irradiation. There were significant differences between the 60 Gy group and the 45 Gy and 30 Gy groups (P < 0.05). To conclude, irradiation with 60 Gy and 45 Gy 32P radionuclide on the back of rats could successfully establish a practically pre-clinical animal model, and the mechanism is related to the up-regulation of P53 and Bax and the down-regulation of Bcl-2. This model can provide a reference for the establishment of animal models for the study of the mechanism of radiation skin injury and its prevention and treatment. [ABSTRACT FROM AUTHOR]

Vibriosis, caused by Vibrio, seriously affects the health of fish, shellfish, and shrimps, causing large economic losses. Teleosts are represent the first bony vertebrates with both innate and adaptive immune responses against pathogens. Aquatic animals encounter hydraulic pressure and more pathogens, compared to terrestrial animals. The skin is the first line of defense in fish, constituting the skin-associated lymphoid tissue (SALT), which belongs to the main mucosa-associated lymphoid tissues (MALT). However, little is known about the function of immunity related proteins in fish. Therefore, this study used iTRAQ (isobaric tags for relative and absolute quantitation) to compare the skin proteome between the resistant and susceptible families of Cynoglossus semilaevis. The protein integrin beta-2, the alpha-enolase isoform X1, subunit B of V-type proton ATPase, eukaryotic translation initiation factor 6, and ubiquitin-like protein ISG15, were highly expressed in the resistant family. The 16S sequencing of the skin tissues of the resistant and susceptible families showed significant differences in the microbial communities of the two families. The protein-microbial interaction identified ten proteins associated with skin microbes, including immunoglobulin heavy chain gene (IGH), B-cell lymphoma/leukemia 10 (BCL10) and pre-B-cell leukemia transcription factor 1 isoform X2 (PBX2). This study highlights the interaction between skin proteins and the microbial compositions of C. semilaevis and provides new insights into understanding aquaculture breeding research. [ABSTRACT FROM AUTHOR]

Background: Primary cutaneous macular amyloidosis (PCMA) is a chronic pruritic cutaneous disease characterized by heterogeneous extracellular deposition of amyloid protein in the skin. Aims: This study aimed to evaluate the efficacy of topical 6% gabapentin cream for the treatment of patients with PCMA. Materials and Methods: In this triple‐blind clinical trial, a total of 34 patients, who were diagnosed with PCMA, treated using two different strategies of topical gabapentin as the active group and vehicle cream as the control group. Results: Pruritus score reduction in both groups was statistically significant compared with the baseline value (p < 0.001). There was a significant pigmentation score reduction in intervention group compared with control group after 1 month of the study (p < 0.001). The differences of pigmentation score changes between the groups were not significant at month 2 (p = 0.52) and month 3 (p = 0.22). Conclusions: The results of this study suggest that topical gabapentin cream may be effective as a topical agent in the treatment of pruritus associated with PCMA without any significant adverse effects. It is recommended to perform similar studies with a larger sample size and longer duration in both sexes. [ABSTRACT FROM AUTHOR]

This paper aims to investigate the impact of CQ on type 2 inflammatory response in MC903-induced AD mice. Methods: An AD mouse model was established via MC903 induction. After CQ treatment, AD mice were intraperitoneally injected with polyinosinic: polycyclic acid [poly (I:C)] or Nigericin. Dermatitis severity was scored, and the thickness of the left ear was measured. The pathological changes in mouse skin tissues were observed by H&E staining. The number of mast cells was counted via TB staining. The content of peripheral blood T-helper 2 (Th2) cells and levels of immunoglobulin E (IgE), thymic stromal-derived lymphopoietin (TSLP), interleukin (IL)-4, IL-13, interferon (IFN)-γ, IL-1β, and IL-18 were assessed by flow cytometry and ELISA. The levels of toll-like receptor 3 (TLR3), NLRP3, ASC, and cleaved caspase-1 proteins in skin tissues were determined by Western blot. Results: CQ treatment abated dermatitis severity and left ear thickness in AD mice, alleviated skin damage, reduced mast cell number, diminished IgE, TSLP, IL-4, and IL-13 levels, and peripheral blood Th2 cell content, with no significant changes in IFN-γ level. CQ alleviated type 2 inflammatory response in AD mice by inhibiting the activation of TLR3. CQ suppressed NLRP3 inflammasome activation. Activating TLR3/NLRP3 annulled CQ-mediated alleviation on type 2 inflammatory response in AD mice. Conclusion: CQ alleviated type 2 inflammatory response in AD mice by inhibiting TLR3 activation and NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Simple Summary: With the rapid progress of laser technology and its expanding applications, there is a growing need for detailed information regarding its effects on living tissue and the treatment of skin damage caused by this kind of radiation. Both collagen levels and apoptosis-related protein expressions were quantitatively and comparatively analyzed in porcine skin injuries induced by laser exposure. The findings revealed skin injuries primarily manifested as white spots and burnt spots. There was a progressive increase in the size and depth of skin damage as the laser dosage was elevated. Laser-induced apoptotic cells in porcine skin injuries were significantly increased in the late stages of healing. Subjection to a 1064 nm laser led to a decline in skin healing efficiency as the radiation dosage escalated, leading to disrupted collagen arrangement and inadequate collagen content. Heightened Bax, caspase-3, and caspase-9 protein expressions in healing skin tissues were directly linked to escalated cell apoptosis. To investigate the associated factors concerning collagen and the expression of apoptosis-related proteins in porcine skin injuries induced by laser exposure, live pig skin was irradiated at multiple spots one time, using a grid-array method with a 1064 nm laser at different power outputs. The healing process of the laser-treated areas, alterations in collagen structure, and changes in apoptosis were continuously observed and analyzed from 6 h to 28 days post-irradiation. On the 28th day following exposure, wound contraction and recovery were notably sluggish in the medium-high dose group, displaying more premature and delicate type III collagen within the newly regenerated tissues. The collagen density in these groups was roughly 37–58% of that in the normal group. Between days 14 and 28 after irradiation, there was a substantial rise in apoptotic cell count in the forming epidermis and granulation tissue of the medium-high dose group, in contrast to the normal group. Notably, the expression of proapoptotic proteins Bax, caspase-3, and caspase-9 surged significantly 14 days after irradiation in the medium-high dose group and persisted at elevated levels on the 28th day. During the later stage of wound healing, augmented apoptotic cell population and insufficient collagen generation in the newly generated skin tissue of the medium-high dose group were closely associated with delayed wound recovery. [ABSTRACT FROM AUTHOR]

Plaque psoriasis, a chronic immune-mediated skin disorder, is characterized by well-demarcated erythematous plaques with silvery scales. This condition stems from complex interactions between genetic predisposition, immune dysregulation, and environmental triggers. Tapinarof downregulates the cytokine IL-17, diminishes the inflammatory infiltrate, and provides antioxidant properties while enhancing the expression of skin barrier proteins. This review begins by assessing tapinarof's mechanism in treating plaque psoriasis. Subsequently, it examines the effectiveness and safety of tapinarof 1% cream in adult patients. Tapinarof 1% cream, which works by activating the aryl hydrocarbon receptor, is an FDA-approved treatment for adult plaque psoriasis. This therapy introduces a novel, nonsteroidal method for addressing inflammation and skin barrier issues, potentially serving as an alternative to conventional treatments. The once-daily, convenient cream formulation and favorable safety profile may enhance patient adherence, which is often poor with topical treatments. Tapinarof also maintains disease clearance for a mean of 4 months after treatment cessation. [ABSTRACT FROM AUTHOR]

Significance: Diabetes can lead to the glycation of proteins and dysfunction of skin collagen. Skin lesions are a prevalent clinical symptom of diabetes mellitus (DM). Early diagnosis and assessing the efficacy of treatment for DM are crucial for patient health management. However, performing a non-invasive skin assessment in the early stages of DM is challenging. Aim: By using the polarization-sensitive optical coherent tomography (PS-OCT) imaging technique, it is possible to noninvasively assess the skin changes caused by diabetes. Approach: The PS-OCT was used to monitor the polarization characteristics of mouse skin at different stages of diabetes. Results: Based on a multi-layered adhesive tape model, we found that the polarization characteristics (retardation, optic axis, and polarization uniformity) were sensitive to the microstructure changes in the samples. Through this method, we observed significant changes in the polarization states of the skin as diabetes progressed. This was in line with the detected microstructure changes in skin collagen fibers using scanning electron microscopy. Conclusions: This study presents a highly useful approach for non-invasive skin assessment of diabetes. [ABSTRACT FROM AUTHOR]

Determining the post-mortem interval (PMI) is one of forensic pathology's primary objectives and one of its most challenging tasks. Numerous studies have demonstrated the accuracy of histomorphology and immunohistochemical investigations in determining the time of death. Nevertheless, the skin, a robust and easy-to-remove tissue, has only been partially analyzed so far. By studying 20 adult male mice, we tried to determine whether post-mortem immunohistochemical detection in the skin of HMGB1 proteins and associated components (Beclin1 and RAGE) could be used for this purpose. We discovered that nuclear HMGB1 overexpression indicates that death occurred within the previous 12 h, nuclear HMGB1 negativization with high cytoplasmic HMGB1 intensity indicates that death occurred between 12 and 36 h earlier and cytoplasmic HMGB1 negativization indicates that more than 48 h have passed since death. RAGE and Beclin1 levels in the cytoplasm also decreased with time. The latter proteins' negativization might indicate that more than 24 and 36 h, respectively, have passed from the time of death. These indicators might potentially be helpful in forensic practice for determining the PMI using immunohistochemistry. [ABSTRACT FROM AUTHOR]

Background: Proteins play a central role in psoriasis as they are involved in the structural phenotypic changes and inflammation that characterize the disease. This systematic review aimed to assess which proteins have been consistently reported as upregulated or downregulated in the skin and blood from patients with psoriasis. Methods: We included proteomic studies reporting differentially expressed proteins (DEPs) in at least one of four predefined comparisons using a standardized procedure to extract and align data. Network analysis of functional protein associations was made with StringApp in Cytoscape. A protocol for this review was registered in the PROSPERO database (ref:CRD42022363226). Results: We identified and assessed 772 studies published between December 2, 1996, and April 28, 2023, among which 30 studies met the inclusion and data availability criteria for analysis that together reported a sum of 5,314 DEPs. The majority of consistently reported upregulated and downregulated proteins were found in lesional versus non-lesional skin (n = 313), followed by lesional versus healthy skin (n = 185), blood from patients with psoriasis versus blood from healthy individuals (n = 140), and non-lesional versus healthy skin (n = 1). Network analysis of upregulated proteins revealed different functional clusters with interleukin (IL)-6, IL-8, IL-17A, C-C motif chemokine (CCL) 20, signal transducer and activator of transcription (STAT) 3, and interferon (IFN)-γ along with less well-studied proteins playing central roles. Some of the reported changes are associated with anti-inflammatory effects. Additionally, the proteomic dysregulation also included antimicrobial peptides, alarmins, angiogenic factors, and proteins related to protein synthesis. Conclusion: Our findings generally support current understandings of the pathological mechanisms in psoriasis. Importantly, some consistent findings have not been discussed before and deserve attention in future research. [ABSTRACT FROM AUTHOR]

Wheat-dependent, exercise-induced anaphylaxis has no fundamental cure and requires patients to refrain from wheat consumption or to rest after eating. Although hypoallergenic wheat production by enzymatic degradation or thioredoxin treatment has been investigated, challenges still exist in terms of labor and efficacy. We investigated a hypoallergenic wheat product manufacturing technology that takes advantage of the property of tannins to bind tightly to proteins. Commercially available bread wheat (BW) and hypoallergenic wheat (1BS-18 "Minaminokaori", 1BS-18M) were used. Chestnut inner skin (CIS) was selected as a tannin material based on the screening of breads with added unused parts of persimmon and chestnut. Hypoallergenicity was evaluated using Western blotting. The effect of CIS addition on the antioxidative properties of bread was also measured. For both BW and 1BS-18M, CIS addition reduced the immunoreactivity of wheat allergens. Antioxidant activities increased with increasing CIS substitution. However, 10% CIS-substituted breads were substantially less puffy. Five percent CIS substitution was optimal for achieving low allergenicity, while maintaining bread quality. The strategy investigated herein can reduce allergies related to wheat bread consumption. In this study, the evaluation of hypoallergenicity was limited to instrumental analysis. In the future, we will evaluate hypoallergenicity through clinical trials in humans. [ABSTRACT FROM AUTHOR]

The monogenetic disease epidermolysis bullosa (EB) is characterised by the formation of extended blisters and lesions on the patient's skin upon minimal mechanical stress. Causal for this severe condition are genetic mutations in genes, leading to the functional impairment, reduction, or absence of the encoded protein within the skin's basement membrane zone connecting the epidermis to the underlying dermis. The major burden of affected families justifies the development of long-lasting and curative therapies operating at the genomic level. The landscape of causal therapies for EB is steadily expanding due to recent breakthroughs in the gene therapy field, providing promising outcomes for patients suffering from this severe disease. Currently, two gene therapeutic approaches show promise for EB. The clinically more advanced gene replacement strategy was successfully applied in severe EB forms, leading to a ground-breaking in vivo gene therapy product named beremagene geperpavec (B-VEC) recently approved from the US Food and Drug Administration (FDA). In addition, the continuous innovations in both designer nucleases and gene editing technologies enable the efficient and potentially safe repair of mutations in EB in a potentially permanent manner, inspiring researchers in the field to define and reach new milestones in the therapy of EB. [ABSTRACT FROM AUTHOR]

Simple Summary: In people, skin allergies to environmental factors have been linked to abnormalities in the skin itself. One of these abnormalities in people is a lower amount of a family of skin proteins called filaggrins. This decrease makes the skin more permeable to the absorption of environmental allergens such as dust mites. In our study, we wanted to use a dog model of skin allergies to study the impact of standardized and repeated dust mite exposures on the skin itself. More specifically, we wanted to see how these exposures would affect filaggrin proteins and compare the response of normal and allergic dogs. We found that the skin of allergic dogs overreacted to dust mite exposure by getting thicker and increasing the production of filaggrins compared to the normal dogs. Despite this extra production of filaggrin, the allergic skin showed more breakdown products of filaggrin. We conclude that allergic skin attempts to compensate for the allergic insult but it is not as efficient as normal skin. Filaggrin is important for the skin barrier and atopic dermatitis. Another filaggrin-like protein, filaggrin 2, has been described. We evaluated antibodies against both filaggrins in normal and atopic skin biopsies from dogs before and after allergen challenges (D0, D1, D3 and D10). Filaggrins expression was evaluated by immunohistochemistry and Western blot. We used PCR to investigate changes in filaggrin gene expression. Effects of group (p = 0.0134) and time (p = 0.0422) were shown for the intensity of filaggrin staining. Only an effect of group was found for filaggrin 2 (p = 0.0129). Atopic samples had higher intensity of staining than normal dogs [filaggrin on D3 (p = 0.0155) and filaggrin 2 on D3 (p = 0.0038) and D10 (p < 0.0001)]. Atopic samples showed increased epidermal thickness after allergen exposure (D3 vs. D0, p = 0.005), while normal dogs did not. In atopic samples, significant increased gene expression was found for filaggrin overtime but not for filaggrin 2. Western blot showed an increase in filaggrin 2 on D3. A small size band (15 kD) containing a filaggrin sequence was found in Western blots of atopic samples only. We conclude that atopic skin reacts to allergen exposure by proliferating and increasing filaggrin production but that it also has more extensive filaggrin degradation compared to normal skin. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa (EB) is a heritable skin blistering disease caused by variants in genes coding for proteins that secure cell–cell adhesion and attachment of the epidermis to the dermis. Interestingly, several proteins involved in inherited EB are also associated with autoimmune blistering diseases (AIBD). In this study, we present a long‐term follow‐up of 15 patients suffering from recessive dystrophic or junctional EB. From these patients, 62 sera were analysed for the presence of autoantibodies associated with AIBD. We show that patients suffering from recessive dystrophic EB (RDEB) are more susceptible to developing autoantibodies against skin proteins than patients suffering from junctional EB (70% vs. 20%, respectively). Interestingly, no correlation with age was observed. Most patients showed reactivity to Type XVII collagen/linear IgA bullous dermatosis autoantigen (n = 5; 33%), followed by BP230 (n = 4; 27%), Type VII collagen (n = 4; 27%) and laminin‐332 (n = 1; 7%). The pathogenicity of these autoantibodies remains a subject for future experiments. [ABSTRACT FROM AUTHOR]

Ferroptosis, a type of programmed cell death, occurs when there is oxidative stress and lipid peroxides. This condition is marked by lipid peroxidation that relies on iron and the reduction of cellular defences against oxidation. To investigate the effect of UVB irradiation on ferroptosis of human keratinocytes HaCaT cells, the cells were pretreated with Ferrostatin 1 (Fer‐1, 10 μM), an ferroptosis inhibitor and then irradiated with UVB (20 mJ/cm2) for 30 min to detect related indexes of ferroptosis through MTT assay, quantitative real‐time polymerase chain reaction, flow cytometry, reactive oxygen species (ROS) assay, western blotting. Results showed that UVB significantly reduced cell activity, promoted apoptosis and ROS level, whereas Fer‐1 significantly increased cell activity, and reduced apoptosis and ROS level. In addition, UVB significantly reduced levels of ferroptosis‐related proteins and skin barrier‐related proteins, and increased levels of γ‐H2AX and iron, whereas Fer‐1 significantly increased their protein levels, and reduced levels of γ‐H2AX and iron. Conjoint analysis of transcriptomic and proteomic revealed that UVB significantly reduced the levels of TIMP metallopeptidase inhibitor 3 (TIMP3), and coagulation factor II thrombin receptor (F2R), whereas Fer‐1 significantly promoted the levels of TIMP3, and F2R. Therefore, our results indicated that Fer‐1 significantly ameliorates UVB‐induced damage of HaCaT cells by regulating the levels of TIMP3 and F2R. [ABSTRACT FROM AUTHOR]

Objectives: We previously revealed the role of tanshinone IIA (TAN IIA) on endothelial cells and the impact of TAN IIA on the endothelial‐to‐mesenchymal transition in systemic sclerosis (SSc). In this study, we sought to further determine whether TAN IIA can directly act on the skin fibroblasts of scleroderma and look into its underlying anti‐fibrotic mechanisms. Methods: Bleomycin was used to establish the SSc mouse model. After TAN IIA treatment, dermal thickness, type I collagen and hydroxyproline content were measured. Primary fibroblasts were acquired from SSc patients and cultured in vitro, and the effects of TAN IIA on proliferation, apoptosis and the cell cycle of fibroblasts were detected. Results: In a bleomycin‐induced SSc model, we discovered that TAN IIA significantly improved skin thickness and collagen deposition, demonstrating a potent anti‐fibrotic action. TAN IIA inhibits the proliferation of skin fibroblasts derived from SSc patients by causing G2/M cell cycle arrest and promoting apoptosis. Additionally, TAN IIA downregulated extracellular matrix gene transcription and collagen protein expression in skin fibroblasts in a dose‐gradient‐dependent manner. Furthermore, we showed how TAN IIA can reduce the activation of the transforming growth factor‐β (TGF‐β)/Smad and mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated kinase (ERK) pathways, which are important factors in SSc. Conclusions: In summary, these data suggest that TAN IIA can reduce SSc‐related skin fibrosis by modulating the TGF‐β/Smad and MAPK/ERK signalling pathways. More importantly, our results imply that TAN IIA can directly act on the skin fibroblasts of SSc, therefore, inhibiting fibrosis. [ABSTRACT FROM AUTHOR]

Recently, particulate matter (PM) has been shown to exacerbate atopic dermatitis (AD) by inducing an inflammatory response. Meanwhile, several studies revealed that exosomes derived from adipose tissue-derived mesenchymal stem cells promote wound healing and alleviate inflammation via their regenerative and immunomodulatory capacities. Our study aimed to investigate the effects of human adipose tissue-derived mesenchymal stem cell-derived (ASC)-exosomes in PM-induced AD. An AD-like triple-cell model was established by treating human keratinocytes, dermal fibroblasts, and mast cells with polyinosinic:polycytidylic acid (Poly I:C) and interleukin 1 alpha (IL-1α). The effects of PM and ASC-exosomes on the expression of pro-inflammatory cytokines and skin barrier proteins were examined using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence. PM increased pro-inflammatory cytokines (IL-6, IL-1β, and IL-1α) and decreased the anti-inflammatory cytokine IL-10, while the mRNA expression of skin barrier proteins (loricrin and filaggrin) decreased. However, when the cells were treated with ASC-exosomes, the PM-induced effects on pro-inflammatory cytokines and skin barrier proteins were reversed. Our results confirmed that PM-induced inflammation and skin barrier damage were alleviated by ASC-exosomes in our AD-like triple-cell model. These data suggest that ASC-exosomes can serve as a therapeutic agent for PM-exacerbated AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by epidermal barrier dysfunction and Th2-skewed inflammation. Campanula takesimana (C. takesimana), a Korean endemic plant grown on Ulleng Island, has long been associated with a traditional alternative medicine for asthma, tonsillitis, and sore throat. In this study, we reported the effect of C. takesimana callus extract on upregulating epidermal barrier-related proteins dysregulated by Th2 cytokines. C. takesimana callus extract induced the expression of skin barrier proteins, such as filaggrin, claudin-1, and zonula occludens-1, in both human primary keratinocytes and Th2-induced AD-like skin-equivalent models. Additionally, RNA sequencing analysis demonstrated that C. takesimana callus extract partially restored Th2 cytokine-induced dysregulation of the epidermal development and lipid metabolic pathways. Considering the advantages of callus as a sustainable eco-friendly source of bioactive substances, and its effect on skin barrier proteins and lipid metabolic pathways, C. takesimana callus extracts can possibly be utilized to improve the integrity of the skin barrier. [ABSTRACT FROM AUTHOR]

Collagen is the major structural protein in the skin. Fragmentation and disorganization of the collagen fibrils are the hallmarks of the aged human skin dermis. These age-related alterations of collagen fibrils impair skin structural integrity and make the tissue microenvironment more prone to skin disorders. As the biological function of collagen lies predominantly in its physical properties, we applied atomic force microscopy (AFM) and nanoindentation to evaluate the physical properties (surface roughness, stiffness, and hardness) of dermal collagen in young (25±5 years, N = 6) and aged (75±6 years, N = 6) healthy sun-protected hip skin. We observed that in the aged dermis, the surface of collagen fibrils was rougher, and fiber bundles were stiffer and harder, compared to young dermal collagen. Mechanistically, the age-related elevation of matrix metalloproteinase-1 (MMP-1) and advanced glycation end products (AGEs) are responsible for rougher and stiffer/harder dermal collagen, respectively. Analyzing the physical properties of dermal collagen as a function of age revealed that alterations of the physical properties of collagen fibrils changed with age (22–89 years, N = 18). We also observed that the reticular dermis is rougher and mechanically stiffer and harder compared to the papillary dermis in human skin. These data extend the current understanding of collagen beyond biological entities to include biophysical properties. [ABSTRACT FROM AUTHOR]

Existing experiments have found a new intergenic lncRNA activated by melatonin, which is called lncRNA MTC. However, the regulatory mechanism of lncRNA MTC in Liaoning Cashmere goat skin fibroblasts has not been clarified. Specific knockdown of lncRNA MTC inhibits cell proliferation and increases apoptosis. iTRAQ reagent was used for relative and absolute quantification of proteins in lncRNA MTC-KD and NC groups to evaluate changes in protein expression during dermal fibroblast development following lncRNA MTC deletion. A total of 5931 proteins were found in Liaoning Cashmere goat skin fibroblasts, of which 123 were differentially expressed, including 32 up-regulated proteins and 91 down-regulated proteins. Of the 91 down-regulated proteins, 32 act mainly through related pathways (e.g., cell cycle, mitochondrial function, ribosomal structure, vesicular transport, cytoskeletal components and skin morphogenesis). LncRNA MTC facilitates the proliferation of Liaoning Cashmere goat skin fibroblasts by regulating ITGB5, TlN2, CTSS, POLG, RAP1B, CHAF1A, CDCA8 and other proteins involved in cell proliferation. The results of this study provide some candidate proteins for the in-depth investigation of the molecular mechanism of lncRNA MTC, which facilitates hair growth in cashmere goats and provides more insights into their regulatory networks and biochemical pathways. [ABSTRACT FROM AUTHOR]