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Keywords = skin formation

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11 pages, 1507 KiB  
Article
Peony Root Extract Controls AGE–RAGE Interaction, Suppresses AGE Formation, and Reduces Skin Dullness
by Kyoko Kanai, Kazal Boron Biswas, Asuka Hirasawa, Misaki Futamura, Kiyotaka Tanaka and Kotaro Sakamoto
Cosmetics 2025, 12(4), 163; https://doi.org/10.3390/cosmetics12040163 - 4 Aug 2025
Viewed by 12
Abstract
Skin dullness contributes to a fatigued and aged appearance, often exceeding one’s biological age. It is a common dermatological concern influenced by aging and poor lifestyle habits, regardless of ethnicity or age. This study aimed to examine advanced glycation end products (AGEs) and [...] Read more.
Skin dullness contributes to a fatigued and aged appearance, often exceeding one’s biological age. It is a common dermatological concern influenced by aging and poor lifestyle habits, regardless of ethnicity or age. This study aimed to examine advanced glycation end products (AGEs) and their receptor (receptor for AGEs [RAGE]) as contributing factors to skin dullness. AGEs themselves have a yellowish hue, contributing to “yellow dullness.” Additionally, AGE–RAGE signaling promotes melanin production in melanocytes and impairs keratinocyte differentiation as a result of inflammation. Therefore, regulating the AGE–RAGE interaction may help reduce skin dullness. Through screening various natural ingredients, we found that peony root extract (PRE) inhibits AGE formation and blocks AGE–RAGE binding. Furthermore, the presence of PRE leads to the suppression of AGE-induced melanin production in melanocytes and the restoration of impaired keratinocyte differentiation in glycated basement membrane components. In a human clinical study, topical application of a 1% PRE-containing lotion for 2 weeks significantly reduced melanin content, with a trend toward decreased AGE accumulation and visible spots on the cheeks. These findings support the potential of PRE as a multifunctional cosmetic ingredient that comprehensively addresses skin dullness by modulating the AGE–RAGE interaction. Full article
(This article belongs to the Special Issue Skin Anti-Aging Strategies)
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16 pages, 1919 KiB  
Article
CampyTube: Seamless Integration of a Molecular Test and Lateral Flow Detection of Campylobacter in a Single Vial
by Natalia Sandetskaya, Andreas Kölsch, Kai Mattern, Vanessa Vater, Dirk Kuhlmeier and Florian Priller
Biosensors 2025, 15(8), 497; https://doi.org/10.3390/bios15080497 - 1 Aug 2025
Viewed by 107
Abstract
Background: The efficient control of hygiene and Campylobacter’s contamination status at various steps of poultry meat production is essential for the prevention of Campylobacter transmission to humans. Microbiological methods are laborious and time-consuming, and molecular methods of detection are often too skill- [...] Read more.
Background: The efficient control of hygiene and Campylobacter’s contamination status at various steps of poultry meat production is essential for the prevention of Campylobacter transmission to humans. Microbiological methods are laborious and time-consuming, and molecular methods of detection are often too skill- and infrastructure-demanding. Methods: We have developed CampyTube, a simple and user-friendly format for the integration of isothermal DNA amplification with embedded instrument-free detection on a miniaturized lateral flow test in a single vial. All test components, from the dry amplification reagents to the mini lateral flow tests, are incorporated into a standard single vial, which is closed after the addition of the liquid sample and never has to be opened again. This ensures the absolute prevention of carry-over contamination and makes the system very safe and simple to use in point-of-need settings. Results: As few as 60 Campylobacter genome copies per reaction could be successfully detected with CampyTube. We have primarily developed and evaluated CampyTube for the detection of Campylobacter in chicken neck skin samples and could reach 100% sensitivity and 100% specificity in the samples exceeding the regulatory limit of 1000 CFU/g confirmed microbiologically, while the sensitivity in all samples that tested positive using qPCR (1.4 × 102–2.5 × 106 genome copies/g) was 71.1%. We discuss the impact of sample preparation on CampyTube performance and suggest further options for test optimization. Conclusions: CampyTube is a highly versatile and efficient, yet simple, affordable, and material-saving system that can be adapted for other targets and sample types. Full article
(This article belongs to the Special Issue Biosensors for Monitoring and Diagnostics)
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28 pages, 13735 KiB  
Article
Immunohistopathological Analysis of Spongiosis Formation in Atopic Dermatitis Compared with Other Skin Diseases
by Ryoji Tanei and Yasuko Hasegawa
Dermatopathology 2025, 12(3), 23; https://doi.org/10.3390/dermatopathology12030023 - 1 Aug 2025
Viewed by 260
Abstract
Whether the spongiotic reaction caused by the interaction of keratinocytes, T-lymphocytes, inflammatory dendritic epidermal cells (IDECs), and Langerhans cells (LCs) observed in atopic dermatitis (AD) represents a common feature of spongiosis in various skin diseases remains unclear. We analyzed the characteristics of spongiosis [...] Read more.
Whether the spongiotic reaction caused by the interaction of keratinocytes, T-lymphocytes, inflammatory dendritic epidermal cells (IDECs), and Langerhans cells (LCs) observed in atopic dermatitis (AD) represents a common feature of spongiosis in various skin diseases remains unclear. We analyzed the characteristics of spongiosis in AD compared with those in other eczematous dermatitis and inflammatory skin diseases by using immunohistochemical methods. Infiltration of IDECs (CD11c+ cells and/or CD206+ cells) and T-lymphocytes, accompanied by degenerated keratinocytes and aggregated LCs (CD207+ cells), was frequently observed as a common feature of spongiosis in multiple conditions. However, IDECs expressing IgE were identified exclusively in IgE-mediated AD. Aggregation of IDECs was predominantly observed in the spongiosis of adaptive immune-mediated eczematous disorders, such as AD and allergic contact dermatitis. These IDEC aggregations constituted the major components of the epidermal dendritic cell clusters seen in AD and other eczematous or eczematoid dermatoses, and may serve as a useful distinguishing marker from Pautrier collections seen in cutaneous T-cell lymphoma. These findings suggest that IDECs, in cooperation with other immune cells, may play a pivotal role in spongiosis formation in AD and various skin diseases, although the underlying immunopathological mechanisms differ among these conditions. Full article
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18 pages, 762 KiB  
Review
Djulis (Chenopodium formosanum) Extract as a Promising Natural Agent Against Skin Aging
by Jia-Ling Lyu, Po-Yuan Wu, Hsiao-Fang Liao, Chia-Lin Lee, Kuo-Ching Wen, Chang-Cheng Chang and Hsiu-Mei Chiang
Molecules 2025, 30(15), 3209; https://doi.org/10.3390/molecules30153209 - 31 Jul 2025
Viewed by 305
Abstract
Photoaging, predominantly induced by ultraviolet radiation, is a primary driver of premature skin aging, characterized by complex molecular mechanisms including oxidative stress, inflammation, matrix metalloproteinase activation, and extracellular matrix degradation. Consequently, there is growing scientific interest in identifying effective natural agents to counteract [...] Read more.
Photoaging, predominantly induced by ultraviolet radiation, is a primary driver of premature skin aging, characterized by complex molecular mechanisms including oxidative stress, inflammation, matrix metalloproteinase activation, and extracellular matrix degradation. Consequently, there is growing scientific interest in identifying effective natural agents to counteract skin aging and photoaging. Djulis (Chenopodium formosanum), an indigenous Taiwanese pseudocereal from the Amaranthaceae family, has emerged as a promising candidate for skincare applications because of its rich phytochemicals and diverse bioactivities. This review describes the current understanding of the molecular mechanisms underlying photoaging and examines the therapeutic potential of djulis extract as a multifunctional agent for skin aging. Its mechanisms of action include enhancing antioxidant defenses, modulating inflammatory pathways, preserving the extracellular matrix, and inhibiting the formation of advanced glycation end products. Bioactive constituents of djulis extract, including phenolic compounds, flavonoids, and betanin, are known to exhibit potent antioxidant and photoprotective activities by modulating multiple molecular pathways essential for skin protection. The bioactivities of djulis in in vitro and animal studies, and four skin clinical trials of djulis extract products are presented in this review article. Ultimately, this review provides an overview that supports the potential of djulis extract in the development of evidence-based skincare formulations for the prevention and treatment of skin aging. Full article
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10 pages, 1920 KiB  
Case Report
Junctional Epidermolysis Bullosa Caused by a Hemiallelic Nonsense Mutation in LAMA3 Revealed by 18q11.2 Microdeletion
by Matteo Iacoviello, Marilidia Piglionica, Ornella Tabaku, Antonella Garganese, Aurora De Marco, Fabio Cardinale, Domenico Bonamonte and Nicoletta Resta
Int. J. Mol. Sci. 2025, 26(15), 7343; https://doi.org/10.3390/ijms26157343 - 29 Jul 2025
Viewed by 293
Abstract
Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the [...] Read more.
Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the “lamina lucida”. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin α6β4 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient’s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G > A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient’s mother, while it was absent in the father’s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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25 pages, 3359 KiB  
Article
In Vitro and In Silico Evaluation of the Anti-Aging Potential of Eugenia uniflora UAE Extracts
by Desy Muliana Wenas, Berna Elya, Sutriyo Sutriyo, Heri Setiawan, Rozana Othman, Syamsu Nur, Nita Triadisti, Fenny Yunita and Erwi Putri Setyaningsih
Molecules 2025, 30(15), 3168; https://doi.org/10.3390/molecules30153168 - 29 Jul 2025
Viewed by 340
Abstract
Skin aging is a natural biological process that can be accelerated by free radical induction, leading to a reduction in skin elasticity and the formation of wrinkles due to the depletion of elastin. Eugenia uniflora (dewandaru) is a promising plant believed to possess [...] Read more.
Skin aging is a natural biological process that can be accelerated by free radical induction, leading to a reduction in skin elasticity and the formation of wrinkles due to the depletion of elastin. Eugenia uniflora (dewandaru) is a promising plant believed to possess anti-aging properties, primarily attributed to its major constituents, myricitrin and quercetin. This study aimed to investigate the anti-elastase and antioxidant properties of Eugenia uniflora stem bark, ripe fruit, and seed extracts. Extracts were obtained using an ultrasound-assisted extraction (UAE) method with 70% ethanol. Quantitative phytochemical analysis involved measuring the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity. Bioactive constituents were identified using LC-MS analysis, and their interactions with target enzymes were further evaluated through in silico molecular docking. The results demonstrated that the E. uniflora seed extract exhibited the highest antioxidant activity, with an IC50 of 5.23 µg/mL (DPPH assay) and a FRAP value of 3233.32 µmol FeSO4/g. Furthermore, the ethanolic seed extract showed significant anti-elastase activity with an IC50 of 114.14 µg/mL. Molecular docking predicted strong potential for several compounds as pancreatic elastase inhibitors, including 5-phenylvaleric acid, 2-(3-phenylpropyl)phenol, n-amylbenzene, 2-aminoadipic acid, and traumatin, each showing a prediction activity (PA) value exceeding 0.6. Notably, these compounds also exhibited inhibitory activity against tyrosinase. These findings collectively underscore the significant promise of E. uniflora seed extract as a novel and natural candidate for pharmacocosmeceutical product development, particularly for anti-aging applications. Full article
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26 pages, 764 KiB  
Review
The Role of Oxidative Stress in Skin Disorders Associated with Alcohol Dependency and Antioxidant Therapies
by Joanna Wróblewska, Anna Długosz, Damian Czarnecki, Wioletta Tomaszewicz, Błażej Błaszak, Joanna Szulc and Weronika Wróblewska
Molecules 2025, 30(15), 3111; https://doi.org/10.3390/molecules30153111 - 25 Jul 2025
Viewed by 496
Abstract
Alcohol dependency is a complex and chronic condition that negatively impacts multiple organ systems, including the skin. A key pathological factor in this process is oxidative stress, leading to progressive cellular damage, chronic inflammation, and accelerated cutaneous aging. Alcohol metabolism generates reactive oxygen [...] Read more.
Alcohol dependency is a complex and chronic condition that negatively impacts multiple organ systems, including the skin. A key pathological factor in this process is oxidative stress, leading to progressive cellular damage, chronic inflammation, and accelerated cutaneous aging. Alcohol metabolism generates reactive oxygen species (ROS), which overwhelm endogenous antioxidant defenses and contribute to a range of skin alterations, including nonspecific changes such as xerosis, erythema, and wrinkle formation, as well as inflammatory and neoplastic skin disorders. Additionally, alcohol-induced alterations of the skin microbiome may further exacerbate skin barrier dysfunction and inflammatory responses. This review explores the biochemical mechanisms and skin microbiome alterations linking alcohol-induced oxidative stress to skin damage and disease. Furthermore, it evaluates the therapeutic potential of antioxidant-based interventions, both natural and synthetic. Antioxidants may offer protective and regenerative effects by scavenging free radicals, modulating inflammatory responses, and enhancing skin barrier function. The paper aims to provide a comprehensive overview of the molecular and microbial interplay between alcohol, oxidative stress, and skin health, while identifying future directions for targeted antioxidant therapy in individuals with alcohol dependency. Full article
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16 pages, 764 KiB  
Review
Biotin Supplementation—The Cause of Hypersensitivity and Significant Interference in Allergy Diagnostics
by Kinga Lis
Nutrients 2025, 17(15), 2423; https://doi.org/10.3390/nu17152423 - 24 Jul 2025
Viewed by 401
Abstract
Biotin (vitamin B7) is a common, naturally occurring water-soluble vitamin. It belongs to the broad group of B vitamins. It is a common ingredient in dietary supplements, cosmetics, medicines, and parapharmaceutical preparations administered orally or applied topically (to the skin, hair, nails). The [...] Read more.
Biotin (vitamin B7) is a common, naturally occurring water-soluble vitamin. It belongs to the broad group of B vitamins. It is a common ingredient in dietary supplements, cosmetics, medicines, and parapharmaceutical preparations administered orally or applied topically (to the skin, hair, nails). The problem of the relationship between vitamin B supplementation and sensitivity seems to be multi-threaded. There is little literature data that would confirm that oral vitamin B supplementation or local exposure to biotin is a significant sensitizing factor. Moreover, it seems that allergy to vitamin B7 is very rare. It is possible, however, that the relationship between biotin and hypersensitivity is not limited to its direct action, but results from its essential metabolic function. Vitamin B7, as a cofactor of five carboxylases, affects the main pathways of cellular metabolism. Both deficiency and excess of biotin can result in metabolic disorders, which can have a significant impact on the homeostasis of the entire organism, including the efficient functioning of the immune system. Dysregulation of immune systems leads to its dysfunctional functioning, which can also lead to sensitization to various environmental antigens (allergens). Biotin is also used as an element of some methodological models in immunochemical tests (in vitro diagnostics), including methods used to measure the concentration of immunoglobulin E (IgE), both total (tIgE) and allergen-specific (sIgE). For this reason, vitamin B7 supplementation can be a significant interfering factor in some immunochemical tests, which can lead to false laboratory test results, both false positive and false negative, depending on the test format. This situation can have a direct impact on the quality and effectiveness of diagnostics in various clinical situations, including allergy diagnostics. This review focuses on the role of biotin in allergic reactions, both as a causative factor (allergen/hapten), a factor predisposing to the development of sensitization to various allergens, and an interfering factor in immunochemical methods used in laboratory diagnosis of hypersensitivity reactions and how it can be prevented. Full article
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15 pages, 3673 KiB  
Article
Photodegradation Assessment of Calcipotriol in the Presence of UV Absorbers by UHPLC/MSE
by Małgorzata Król, Paweł Żmudzki, Adam Bucki and Agata Kryczyk-Poprawa
Appl. Sci. 2025, 15(15), 8124; https://doi.org/10.3390/app15158124 - 22 Jul 2025
Viewed by 367
Abstract
Calcipotriol, a synthetic vitamin D3 analogue widely used in psoriasis treatment, requires a detailed stability assessment due to its topical application and potential exposure to UV radiation. As a drug applied directly to the skin, calcipotriol is particularly susceptible to photodegradation, which [...] Read more.
Calcipotriol, a synthetic vitamin D3 analogue widely used in psoriasis treatment, requires a detailed stability assessment due to its topical application and potential exposure to UV radiation. As a drug applied directly to the skin, calcipotriol is particularly susceptible to photodegradation, which may affect its therapeutic efficacy and safety profile. The present study focuses on the analysis of calcipotriol photostability. An advanced UHPLC/MSE method was employed for the precise determination of calcipotriol and its degradation products. Particular attention was given to the effects of commonly used organic UV filters—approved for use in cosmetic products in both Europe and the USA (benzophenone-3, dioxybenzone, meradimate, sulisobenzone, homosalate, and avobenzone)—on the stability of calcipotriol. Unexpected degradation of calcipotriol was observed in the presence of sulisobenzone. Importantly, this effect was consistently detected in methanolic solution and in the pharmaceutical formulation containing calcipotriol and betamethasone, which is particularly significant from a practical perspective. This finding underscores the necessity of evaluating photostability under real-life conditions, as cosmetic ingredients, when co-applied with topical drugs on the skin, may substantially influence the stability profile of the pharmaceutical active ingredient. The research resulted in the first-time characterization of four degradation products of calcipotriol. The degradation process was found to primarily affect the E-4-cyclopropyl-4-hydroxy-1-methylbut-2-en-1-yl moiety, causing its isomerization to the Z isomer and the formation of diastereomers with either the R or S configuration. Computational analyses using the OSIRIS Property Explorer indicated that none of the five degradation products exhibit a toxicity effect, whereas molecular docking studies suggested possible binding of two of the five degradation products of calcipotriol with the VDR. Full article
(This article belongs to the Section Chemical and Molecular Sciences)
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17 pages, 3083 KiB  
Article
Antioxidant and Photoprotective Activities of Viola philippica Polyol Extracts
by Jiang Li, Jiancheng Ma, Ya Li, Lan Luo, Wenhuan Zhang, Yong Tian, Yuncai Tian, Yi Li, Zhongjuan Wang and Mingyi Wu
Antioxidants 2025, 14(7), 884; https://doi.org/10.3390/antiox14070884 - 18 Jul 2025
Viewed by 375
Abstract
Viola philippica (VP), a traditional Chinese medicinal herb widely used for its antibacterial and antioxidant properties, has recently garnered attention for its potential in skin photoprotection. VP was extracted using glycerol (GLY), 1,3-propanediol (PDO), and 1,3-butanediol (BDO) at concentrations of 30%, 60%, and [...] Read more.
Viola philippica (VP), a traditional Chinese medicinal herb widely used for its antibacterial and antioxidant properties, has recently garnered attention for its potential in skin photoprotection. VP was extracted using glycerol (GLY), 1,3-propanediol (PDO), and 1,3-butanediol (BDO) at concentrations of 30%, 60%, and 90% (w/w) to evaluate its antioxidant and UV-protective properties. The total phenolic content (TPC) and total flavonoid content (TFC) of the nine extracts ranged from 34.73 to 71.45 mg GAEs/g and from 26.68 to 46.68 mg REs/g, respectively, with the highest TPC observed in 90% PDO and the highest TFC in 60% GLY. Antioxidant assays revealed IC50 values of 0.49–1.26 mg/mL (DPPH), 0.10–0.19 mg/mL (ABTS), and 1.58–460.95 mg/mL (OH). Notably, the 60% GLY, 30% PDO, and 90% PDO extracts demonstrated notable protective effects against UVB-induced cell damage, reducing intracellular ROS levels and preventing DNA damage. RNA-seq analysis revealed that the protective effects were associated with the modulation of key molecular pathways, including neutrophil extracellular trap formation and TNF, IL-17, and HIF-1 signaling. These findings suggest that Viola philippica polyol extracts, particularly those using 60% GLY, 30% PDO, and 90% PDO, have promising potential for skin photoprotection and could be utilized as natural antioxidants in cosmetic formulations. Full article
(This article belongs to the Special Issue Antioxidants for Skin Health)
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17 pages, 5077 KiB  
Article
Genomic Features and Tissue Expression Profiles of the Tyrosinase Gene Family in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis)
by Yanchao Liu, Pan Liu, Tong Ren, Yang Gao, Ziman Wang, Junxian Zhu, Chen Chen, Liqin Ji, Xiaoyou Hong, Xiaoli Liu, Chengqing Wei, Xinping Zhu, Zhangjie Chu and Wei Li
Genes 2025, 16(7), 834; https://doi.org/10.3390/genes16070834 - 17 Jul 2025
Viewed by 311
Abstract
In farmed animals, body color is not only an ecological trait but also an important trait that influences the commercial value of the animals. Melanin plays an important role in the formation of body color in animals, while the tyrosinase (TYR) gene family is [...] Read more.
In farmed animals, body color is not only an ecological trait but also an important trait that influences the commercial value of the animals. Melanin plays an important role in the formation of body color in animals, while the tyrosinase (TYR) gene family is a group of key enzymes that regulate melanogenesis. The Chinese soft-shelled turtle (Pelodiscus sinensis) is one of the most important reptiles in freshwater aquaculture. However, the potential role of the TYR gene family in the body color formation of P. sinensis remains unclear. This study aimed to investigate the expression and conservation of the TYR gene family in relation to body color variation in P. sinensis. Three core members of this gene family were identified from the P. sinensis genome. Following identification, the genomic features were analyzed. They shared similar physicochemical properties and conserved domains. Chromosome mapping showed that the three genes of P. sinensis were all located on the autosomes, while phylogenetic and collinearity analysis suggested that the protein functions of the three genes in the studied species were highly conserved. Amino acid sequence alignment indicated high conservation among the three TYR gene family proteins (TYR, TYRP1, and DCT) in multiple critical regions, particularly in their hydrophobic N-/C-terminal regions and cysteine/histidine-rich conserved domains. The qRT-PCR revealed that the TYR and DCT genes were highly expressed in the eyes of individuals with different body colors. The expression levels of TYR and TYRP1 genes in the skin were significantly higher in dark-colored individuals than in light-colored ones (p < 0.05). These results will lay the groundwork for functional studies and breeding programs targeting color traits in aquaculture. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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18 pages, 1680 KiB  
Article
IL-2 Complex Therapy Mitigates Humoral Rejection of Fully Mismatched Skin Allografts by Inhibiting IgG Alloantibody Formation
by Konstantinos Mengrelis, Mario Wiletel, Romy Steiner, Anna M. Weijler, Laurenz Wolner, Valentina Stolz, Milos Nikolic, Daniel Simon, Florian Frommlet, Jonathan Sprent, Hannes Stockinger and Nina Pilat
Cells 2025, 14(14), 1086; https://doi.org/10.3390/cells14141086 - 16 Jul 2025
Viewed by 472
Abstract
Antibody-mediated rejection (ABMR) caused by donor-specific Abs (DSAs) is still the leading cause of late graft loss following clinical organ transplantation, and effective strategies to combat ABMR are still elusive. We previously showed that rIL-2 complexed with anti-IL-2 mAb clone JES6-1A12 (IL-2 cplx) [...] Read more.
Antibody-mediated rejection (ABMR) caused by donor-specific Abs (DSAs) is still the leading cause of late graft loss following clinical organ transplantation, and effective strategies to combat ABMR are still elusive. We previously showed that rIL-2 complexed with anti-IL-2 mAb clone JES6-1A12 (IL-2 cplx) leads to the selective expansion of regulatory T cells (Tregs) and the prolonged survival of MHC-mismatched skin allografts. Although the grafts were eventually rejected, mice failed to develop DSAs. Here, we investigated the impact of IL-2 cplx on the humoral response and germinal center (GC) reaction during allograft rejection. IL-2 cplx treatment prevents Bcl-6 upregulation, leading to suppressed development of GC T and B cells. The IL-2 cplx-induced impairment of GC development limits IgG allo-Ab production but allows for IgM synthesis. By employing a hapten–carrier system to investigate affinity maturation, we found that IL-2 cplx induces a distinct shift in specific Ab production favoring low-affinity IgM while simultaneously decreasing IgG responses. These findings illuminate the potential of IL-2 cplx therapy for inducing humoral tolerance, potentially paving the way for refining strategies aimed at preventing and treating ABMR. Full article
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23 pages, 6291 KiB  
Article
Application of Standardized Rosa damascena Stem Cell-Derived Exosomes in Dermatological Wound Healing and Scar Management: A Retrospective Case-Series Study with Long-Term Outcome Assessment
by Lidia Majewska, Agnieszka Kondraciuk, Karolina Dorosz and Agnieszka Budzyńska
Pharmaceutics 2025, 17(7), 910; https://doi.org/10.3390/pharmaceutics17070910 - 14 Jul 2025
Cited by 2 | Viewed by 728
Abstract
Background: Scar formation and impaired wound healing represent significant challenges in dermatology and aesthetic medicine, with limited effective treatment options currently available. Objectives: To evaluate the efficacy and long-term outcomes of Damask rose stem-cell-derived exosome (RSCE) therapy in the management of [...] Read more.
Background: Scar formation and impaired wound healing represent significant challenges in dermatology and aesthetic medicine, with limited effective treatment options currently available. Objectives: To evaluate the efficacy and long-term outcomes of Damask rose stem-cell-derived exosome (RSCE) therapy in the management of diverse dermatological conditions, including traumatic wounds, surgical scars, and atrophic acne scars. Methods: We conducted a case series study from June 2023 to November 2024, documenting four cases with different types of skin damage treated with lyophilized RSCE products. Treatment protocols included a variety of delivery methods such as topical application, microneedling, and post-procedure care. Follow-up assessments were performed at intervals ranging from 7 days to 10 months. Results: All patients demonstrated significant improvements in scar appearance, skin elasticity, hydration, and overall tissue quality. In traumatic facial injury, RSCE therapy facilitated reduction in scar contracture and improved functional outcomes. For atrophic acne scars, comparative treatment of facial sides showed enhanced results with RSCE addition. Acute wounds exhibited accelerated healing with reduced inflammation, while chronic wounds demonstrated improved epithelialization and long-term scar quality. Conclusions: This case series provides preliminary evidence suggesting that RSCE therapy may offer significant benefits in wound healing and scar management. The observed improvements in tissue regeneration, inflammatory modulation, and long-term aesthetic outcomes warrant further investigation through controlled clinical trials. Full article
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18 pages, 20761 KiB  
Article
Integrated Meta-Analysis Identifies Keratin Family Genes and Associated Genes as Key Biomarkers and Therapeutic Targets in Metastatic Cutaneous Melanoma
by Sumaila Abubakari, Yeşim Aktürk Dizman and Filiz Karaman
Diagnostics 2025, 15(14), 1770; https://doi.org/10.3390/diagnostics15141770 - 13 Jul 2025
Viewed by 464
Abstract
Background/Objectives: Cutaneous melanoma is one of the aggressive forms of skin cancer originating from melanocytes. The high incidence of melanoma metastasis continues to rise, partly due to the complex nature of the molecular mechanisms driving its progression. While melanomas generally arise from melanocytes, [...] Read more.
Background/Objectives: Cutaneous melanoma is one of the aggressive forms of skin cancer originating from melanocytes. The high incidence of melanoma metastasis continues to rise, partly due to the complex nature of the molecular mechanisms driving its progression. While melanomas generally arise from melanocytes, we investigated whether aberrant keratinocyte differentiation pathways—like cornified envelope formation—discriminate primary melanoma from metastatic melanoma, revealing novel biomarkers in progression. Methods: In the present study, we retrieved four datasets (GSE15605, GSE46517, GSE8401, and GSE7553) associated with primary and metastatic melanoma tissues and identified differentially expressed genes (DEGs). Thereafter, an integrated meta-analysis and functional enrichment analysis of the DEGs were performed to evaluate the molecular mechanisms involved in melanoma metastasis, such as immune cell deconvolution and protein-protein interaction (PPI) network construction. Hub genes were identified based on four topological methods, including ‘Betweenness’, ‘MCC’, ‘Degree’, and ‘Bottleneck’. We validated the findings using the TCGA-SKCM cohort. Drug-gene interactions were evaluated using the DGIdb, whereas structural druggability was assessed using the ProteinPlus and AlphaFold databases. Results: We identified a total of eleven hub genes associated with melanoma progression. These included members of the keratin gene family (e.g., KRT5, KRT6A, KRT6B, etc.). Except for the gene CDH1, all the hub genes were downregulated in metastatic melanoma tissues. From a prognostic perspective, these hub genes were associated with poor prognosis (i.e., unfavorable). Using the Human Protein Atlas (HPA), immunohistochemistry evaluation revealed mostly undetected levels in metastatic melanoma. Additionally, the cornified envelope formation was the most enriched pathway, with a gene ratio of 17/33. The tumor microenvironment (TME) of metastatic melanomas was predominantly enriched in NK cell–associated signatures. Finally, several hub genes demonstrated favorable druggable potential for immunotherapy. Conclusions: Through integrated meta-analysis, this study identifies transcriptional, immunological, and structural pathways to melanoma metastasis and highlights keratin family genes as promising biomarkers for therapeutic targeting. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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16 pages, 1884 KiB  
Article
The Mechanism of Protective Action of Plant-Derived Squalane (2,6,10,15,19,23-Hexamethyltetracosane) Against UVA Radiation-Induced Apoptosis in Human Dermal Fibroblasts
by Katarzyna Wolosik, Magda Chalecka, Gabriela Gasiewska, Jerzy Palka and Arkadiusz Surazynski
Antioxidants 2025, 14(7), 853; https://doi.org/10.3390/antiox14070853 - 11 Jul 2025
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Abstract
Ultraviolet A (UVA) radiation has been identified as a significant factor contributing to skin photoaging and skin diseases, operating through the excessive generation of reactive oxygen species (ROS) and the subsequent induction of DNA damage. Plant-derived antioxidants have demonstrated efficacy in mitigating UVA-induced [...] Read more.
Ultraviolet A (UVA) radiation has been identified as a significant factor contributing to skin photoaging and skin diseases, operating through the excessive generation of reactive oxygen species (ROS) and the subsequent induction of DNA damage. Plant-derived antioxidants have demonstrated efficacy in mitigating UVA-induced damage; nevertheless, their instability limits their therapeutic potential. This study investigates the mechanisms of antioxidant and cytoprotective effects of squalane (Sq), a stable, plant-derived triterpene, in human dermal fibroblasts (HDFs) exposed to UVA radiation. Sq was administered at concentrations ranging from 0.005% to 0.015% prior to UVA exposure (10 J/cm2). It has been found that Sq counteracted UVA-induced ROS formation, decreased the level of reduced thiol groups, activated apoptosis, and inhibited DNA biosynthesis. Immunofluorescence analysis revealed that Sq suppressed the UVA-induced expression of p53, caspase-3, caspase-9, and PARP, while restoring the activity of the pro-survival p-Akt/mTOR pathway. The findings indicate that Sq exerts protective effects on UVA-induced fibroblast damage through a combination of antioxidant and anti-apoptotic mechanisms. Full article
(This article belongs to the Special Issue Antioxidant Phytochemicals for Promoting Human Health and Well-Being)
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