Search Results (284)

Aquaporins (AQPs) are a family of small integral membrane proteins that mediate the selective transport of water and, in some cases, small solutes such as glycerol and hydrogen peroxide. In the skin, distinct AQP isoforms are expressed throughout the epidermis, dermis, and hypodermis, where they play key roles in maintaining hydration, regulating keratinocyte and fibroblast proliferation, modulating inflammatory responses, and preserving overall tissue integrity. Increasing evidence indicates that aberrant AQP expression or function contributes to skin carcinogenesis, influencing tumor initiation, local invasion, metastasis, and responses to microenvironmental stress. Alterations in specific AQP isoforms have been associated with both major classes of cutaneous malignancies—non-melanoma skin cancers (NMSC), including basal cell carcinoma and squamous cell carcinoma, as well as malignant melanoma (MM)—yet their mechanistic contributions remain incompletely understood. This review synthesizes current knowledge on the involvement of each AQP isoform in skin cancer pathogenesis and progression, integrating findings from molecular, cellular, and in vivo studies. By clarifying the diverse roles of AQPs in cutaneous malignancies, this work aims to support the development of targeted interventions and guide future research in this rapidly evolving field. Full article

Despite advances in the treatment of cutaneous melanoma, there is still a high percentage of patients who fail to respond or develop resistance to treatment. Establishing robust in vitro melanoma models will enable mechanism-based drug screening while reducing animal testing. In this work, a three-dimensional (3D) melanoma skin model (3DMSM) was developed on a porous scaffold. The culture of three melanoma cell lines (SKMEL-1, A375, and G361) in co-culture with human fibroblasts, melanocytes, and keratinocytes allowed the formation of the dermis, and stratified epidermis. Tumors were established in this model using two methodologies: adding previously formed melanoma cell aggregates (CA) or seeding melanoma cells directly into the dermis (CD). In this model, melanoma cells remain in their original microenvironment and, after proliferation, invade the basal layer. The model recapitulates correct melanocyte localization, epidermal disruption, extracellular matrix (ECM) remodeling, including collagen deposition, and epithelial-to-mesenchymal transition (EMT). Additionally, the cytokine profiles studied indicate that the model could mirror the inflammatory and immune-evasive traits of melanoma. Overall, 3DMSM provides a useful tool for understanding the mechanisms of melanoma progression and invasion, and for developing personalized medicine strategies through the implementation of a patient-derived model. Full article

Male pattern baldness (MPB) is a highly prevalent condition with a complex, poorly understood molecular basis that limits therapeutic innovation. This study aimed to bridge the gap between statistical genetic associations and biological function by identifying and prioritizing causal proteins and pathways involved in MPB. Using data from 24,069 men in the UK Biobank, we performed a proteome-wide association study of 2911 plasma proteins with self-reported MPB severity via multivariable ordinal logistic regression, adjusting for age, Body Mass Index (BMI), ethnicity, lifestyle, socioeconomic factors, and testosterone levels. Significant proteins underwent pathway enrichment analysis. Genetic integration included MAGMA for gene-level aggregation and tissue prioritization, transcriptome-wide association studies (TWAS) with GTEx models, conditional fine-mapping, and validation in an independent scalp biopsy transcriptomics dataset (GSE90594). Druggability and pleiotropy were evaluated using databases and phenome-wide association studies. Forty-seven proteins were significantly associated with MPB severity, enriched in pathways involving epidermis development, hair cycle regulation, and cell adhesion. Multi-omic integration prioritized five independent candidate genes: CD38, FGF5, TACSTD2, DPEP1, and PLB1. Transcriptomic validation confirmed differential expression in balding scalp for CD38 (upregulated) and TACSTD2, PLB1 (downregulated). CD38 was identified as druggable with low pleiotropic risks. This study elucidates the molecular architecture of MPB, revealing novel biological pathways beyond canonical androgen signaling. By prioritizing promising non-hormonal targets like CD38, our findings provide a robust, evidence-based framework to guide the development of future therapeutic interventions for this common condition. Full article

Background: Paeonia lactiflora Pall. produces substantial quantities of nectar during the bud stage. In the production of cut flowers, this nectar attracts contaminants that compromise the quality of the flowers. The current practice of rinsing flowers with clean water escalates production costs. Consequently, reducing nectar secretion during the bud stage has emerged as a significant technical challenge for the industry. Nonetheless, insufficient fundamental knowledge concerning the structure of P. lactiflora nectaries and the physiology of nectar secretion impedes the development of pertinent regulatory technologies. Methods: This study established a “nectar secretion index” to evaluate nectar production in various P. lactiflora cultivars. Nectar sugar concentration and composition were measured using a refractometer and gas chromatography–mass spectrometry (GC-MS). Observations of changes in nectary epidermal morphology and anatomical structure during nectar secretion were conducted using scanning electron microscopy and light microscopy. Key Results: The quantity of nectar secreted by various P. lactiflora cultivars can differ. The indices were not significantly correlated with flowering period, flower color, or flower type. At the peak of nectar secretion, the sugar concentration of nectar secretion by different cultivars’ flower buds varied. Sucrose is the primary sugar component in this nectar. Nectar is secreted along the basal margins of the bracts and sepals on the abaxial surface of all cultivars. Specialized raised stomata are located on the upper epidermis, through which nectar is secreted. In contrast, the epidermal stomata located outside nectar-secreting areas exhibit a normal morphology. Specialized stomata do not secrete nectar concurrently. The stomatal aperture and the percentage of nectar-secreting stomata at the secretion sites are significantly higher in high-nectar-producing cultivars than in low-nectar-producing cultivars. Anatomical observations of bract nectaries indicate that, irrespective of nectar production levels, specialized stomata are consistently located adjacent to vascular bundles. During the initial stage of nectar secretion, no starch was detected in the bract nectaries. In contrast, the stomata in non-secretory epidermal cells of bracts maintain a normal morphology, and calcium oxalate crystals were observed within the subepidermal tissues. Throughout the nectar secretion process, the content of photosynthetic pigments and the Fv/Fm ratio in the bracts and sepals of various cultivars correlated with nectar secretion volume. Conclusions: This study, informed by observations of numerous P. lactiflora cultivars, elucidates the structural characteristics of its nectaries and the nectar secretion properties of various cultivars during the bud stage. It confirms that these nectaries are classified as extrafloral nectaries, specifically structural nectaries consisting of specialized raised stomata and closely associated vascular bundles beneath them. No significant differences in nectary structure or location were noted among cultivars with differing nectar yields. However, both the aperture of nectary stomata and the percentage of nectar-secreting stomata exhibited a significant positive correlation with secretion levels. The intrinsic photosynthetic potential at the nectary sites varies significantly among cultivars. The nectar is not derived from stored cellular starch but likely originates simultaneously from both photosynthesis and phloem transport. These findings provide a theoretical foundation for the development of subsequent regulatory technologies. Full article

Chitinases are crucial in the molting process of insects and represent potential targets for the development of RNA interference (RNAi)-based insecticidal strategies. In this study, we identified and characterized 11 chitinase genes (TaChts) in T. absoluta, each harboring at least one GH18 catalytic domain. Phylogenetic analysis placed these proteins into 11 established groups (I-X and h), revealing conserved lineage-specific patterns. Spatiotemporal expression profiling showed that most TaChts peak during key developmental transitions. TaCht1, TaCht2, TaCht3, TaCht5, TaCht6, TaCht7, TaCht10, TaCht-h, and TaIDGF were predominantly expressed in the integument, whereas TaCht8 and TaCht11 showed gut-enriched expression, indicating functional specialization. Stage-tailored RNAi assays demonstrated that silencing TaCht5, TaCht7, TaCht10, and TaIDGF caused pronounced mortality in both larvae and pupae. In larvae, delivery of dsRNA using carbon quantum dots (CQDs) disrupted molting: knockdown of TaCht7, TaCht10, and TaIDGF prevented shedding of the old cuticle, whereas TaCht5 silencing produced severe cuticular shrinkage and blackening. Hematoxylin and eosin staining revealed detachment of epidermal cells from the cuticle, providing cytological evidence of disrupted cuticle–epidermis remodeling. In pupae, microinjection of dsRNA induced cuticular collapse, melanization, and eclosion failure due to persistent adhesion of the pupal case, accompanied by marked reductions in chitinase activity. Together, our findings highlight the critical roles of four key chitinases in endocuticular turnover and metamorphic progression in T. absoluta, offering mechanistic insight into chitin-mediated developmental processes. The identified genes represent strong candidates for RNAi-based, species-specific pest management strategies against this globally significant insect. Full article

There have been few reports of neoplasia in kangaroos to date. In this report, we describe a 13-year-old male captive Red kangaroo (Osphranter rufus) that developed a mass on the right side of the cloacal aperture. Histopathological analysis of a biopsy of the mass revealed proliferating, neoplastic epithelial islands with necrotic centres infiltrating a moderately desmoplastic dermis. The islands were generally large with extensive central caseation necrosis consisting of cellular debris and innumerable neutrophils. The neoplastic epithelial cells resembled the basal cells observed in the basal layer of the epidermis and were characterised by scant to moderate eosinophilic cytoplasm with indistinct cytoplasmic margins. The diagnosis was basal cell carcinoma (BCC). This is the first report of a BCC in a kangaroo, and we compare the findings with that seen in dogs, cats and humans. Full article

Mucosal melanoma (MM) is a rare, aggressive cancer whose incidence has increased continuously over the years. This subtype of melanoma arises from melanocytes on hairless surfaces, typically in the respiratory tract, gastrointestinal (GI) tract, and urogenital tract. The most common sites of occurrence include the head and neck, the anorectal region, and the vulvovaginal region, while the rare sites of MM are the urinary tract and the upper and lower GI tract, including the esophagus, duodenum and the gallbladder. MM arises in melanocytes of the ectodermal mucosa that originate from neural crest cells and migrate through embryonic mesenchyme to their destination. Although melanocytes are located mainly in the epidermis and dermis, their presence in various extracutaneous sites, such as the eyes, mucosal tissue, and leptomeninges, is known. Although both cutaneous melanoma (CM) and MM differ in their epidemiology, genetic profile, and clinical presentation, their treatment options are similar. In contrast to the higher treatment response of CM, MM is characterized by a lower response rate to available treatment options, resulting in a poorer survival rate. In this review, we provide an overview of the biology of MM and the mechanisms regulating its development, progression and treatment resistance. Full article

Background: Cystic echinococcosis (CE) is a globally distributed zoonosis triggered by the larval stage of Echinococcus granulosus (E. granulosus), impacting humans and an extensive array of mammalian intermediate hosts. EGR-01664 is the major egg antigen of E. granulosus, but almost nothing is currently known about the function of EGR-01664 from E. granulosus. Methods: This study aimed to investigate the E. granulosus EGR-01664 gene (GenBank ID: 36337379), and the recombinant EGR-01664 protein was expressed successfully. Next, the transcription of the EGR-01664 gene across various developmental stages of E. granulosus was analyzed. Its spatial expression patterns in adult worms and protoscoleces were characterized using both quantitative PCR (qPCR) and immunofluorescence assays. Furthermore, the immunomodulatory effects of rEGR-01664 on cell proliferation, nitric oxide production, and cytokine secretion were examined by co-culturing the recombinant protein with canine PBMCs. Results: The rEGR-01664 could be recognized by sera from dogs infected with E. granulosus. Immunofluorescence assay (IFA) localization revealed the protein’s presence in the epidermis of protoscoleces, the adult epidermis, and some parenchymal tissues. qPCR revealed that EGR-01664 mRNA levels were significantly higher in protoscoleces compared to adults (p < 0.0001). At a concentration of 20 μg/mL, rEGR-01664 could significantly activate the transcription and expression of IL-10, TGF-β1, IL-17A, and Bax in canine PBMCs. However, with an increase in concentration, it inhibited the expression of IFN-γ, Bcl-2, GSDMD, IL-18, and IL-1β. These results suggest that the EGR-01664 gene plays a crucial role in the development, parasitism, and reproduction of E. granulosus. In vitro studies have shown that rEGR-01664 protein regulates the immune regulation function of canine PBMCs, suggesting its potential as a vaccine adjuvant or immunotherapy target. Conclusions: EGR-01664 may modulate canine PBMC functions to regulate host immune responses, thereby facilitating our understanding of how E. granulosus EGR-01664 contributes to the mechanism of parasitic immune evasion. Full article

High-intensity focused ultrasound (HIFU) has recently emerged as a novel non-invasive treatment modality in dermatology, offering precise ablation of cutaneous lesions with minimal damage to surrounding tissue. Originally developed for deep-seated tumors, dermatological HIFU platforms operating at ~20 MHz enable submillimeter-scale treatment of thermal or mechanical injuries localized to the epidermis and superficial dermis, making them suitable for managing benign, premalignant, and malignant skin conditions. This review outlines the mechanistic basis of HIFU—including thermal coagulation, acoustic cavitation, and immunomodulatory effects—and presents the current evidence for its efficacy in treating actinic keratoses and basal cell carcinomas (BCCs), where early studies report clearance rates of 70–97% and excellent cosmetic outcomes. Compared to conventional therapies such as surgery, photodynamic therapy, or cryotherapy, HIFU offers reduced procedural pain, faster healing, and the ability to treat multiple lesions in a single session. Its role in field cancerization and potential utility in prophylaxis for high-risk skin areas are also explored. While promising, long-term oncologic outcomes and standardized treatment protocols remain under investigation. HIFU represents a significant advancement in non-invasive skin cancer management, aligning oncologic efficacy with patient-centered care. Full article

The development of dressing materials mainly protects the wound, prevents infection, and assists in wound healing. Apart from the most common gauze on the market, different dressing materials can accelerate wound healing. Bacterial cellulose (BC) dressings have had many related studies and applications so far, and other natural or artificial compounds that are beneficial to tissue repair may also be added during the manufacturing process. This study compared the wound healing efficacies of BC dry membrane developed by our team, gauze, commercially available “Tegaderm^TM Hydrocolloid Dressing”, and “AQUACEL^® EXTRA Hydrofiber Dressing”. This study used rats as experimental animals and injured them by scalding. Moreover, Staphylococcus aureus was used to infect wounds to compare the effects on wound healing. We first used NIH-3T3 cells for an in vitro model to confirm that the BC membrane is not harmful to cells. In the animal experiment, wounds were created by scalding and then treated with different dressing materials and doses of S. aureus. After 10 days of treatment, the wound recovery in the BC membrane and AQUACEL^® groups was the most obvious, including angiogenesis in the dermal layer and regeneration of the epidermis layer. Especially without S. aureus infection, inflammatory markers such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression levels were reduced to those of healthy tissue. In conclusion, we confirmed that the BC dry membrane can accelerate wound healing. In the future, it may provide high-efficiency and less expensive options in the dressing market. Full article

This study presents the development of an advanced three-dimensional (3D) bioprinted skin scaffold integrating sodium alginate (SA), gelatin (Gel), human skin-derived decellularized extracellular matrix (dECM), and microbiota-derived postbiotics. To ensure a biocompatible and functional ECM source, human skin samples collected during elective aesthetic surgical procedures were utilized. Following enzymatic treatment, the dermal layer was carefully separated from the epidermis and subjected to four different decellularization protocols. Among them, Protocol IV emerged as the most suitable, achieving significant DNA removal while maintaining the structural and biochemical integrity of the ECM, as confirmed by Fourier-transform infrared spectroscopy. Building on this optimized dECM-4, microbiota-derived postbiotics from Limosilactobacillus reuteri EIR/Spx-2 were incorporated to further enhance the scaffold’s bioactivity. Hybrid scaffolds were then fabricated using 7% Gel, 2% SA, 1% dECM-4, and 40 mg/mL postbiotics in five-layered grid structures via 3D bioprinting technology. Although this composition resulted in reduced mechanical strength, it exhibited improved hydrophilicity and biodegradability. Moreover, antimicrobial assays demonstrated inhibition zones of 16 mm and 13 mm against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) and Pseudomonas aeruginosa (ATCC 27853), respectively. Importantly, biocompatibility was confirmed through in vitro studies using human keratinocyte (HaCaT) cells, which adhered, proliferated, and maintained normal morphology over a 7-day culture period. Taken together, these findings suggest that the engineered hybrid scaffold provides both regenerative support and antimicrobial protection, making it a strong candidate for clinical applications, particularly in the management of chronic wounds. Full article

UVB radiation penetrates the epidermis and upper dermis, compromising skin barrier function. This activates pro-inflammatory cells, releasing mediators (e.g., histamine, interleukins) that induce edema. UVB also generates excessive reactive oxygen species (ROS), causing oxidative stress in skin cells. Although the mechanisms of UV-induced skin damage have been extensively studied, the development of effective UV-protective drugs remains a significant challenge. Scutellarin, a flavonoid glycoside predominantly isolated from Erigeron breviscapus, has demonstrated diverse bioactivities including anti-inflammatory, antioxidant, and anti-tumor effects. However, its role in UVB-induced skin damage has not been fully explored. Therefore, we established a UVB-induced skin damage model in mice by irradiating the dorsal skin with a dose of 300 mJ/cm² UVB. Through measurements of transepidermal water loss, detection of barrier-related proteins, assessment of inflammatory factors, and evaluation of oxidative stress indicators, we found that scutellarin can maintain barrier integrity, reduce skin edema, suppress inflammatory responses, and decrease oxidative stress. Moreover, RNA sequencing of mice skin revealed that scutellarin can modulate inflammatory responses and maintain extracellular matrix homeostasis to alleviate skin damage. These findings suggest that scutellarin is a natural compound with potential for UV-protective effects on the skin. Full article

Background: Skin mycoses affect approximately 10% of the global population, and the range of effective topical antifungal agents remains limited. Voriconazole (VRC) is a broad-spectrum triazole with proven efficacy against drug-resistant fungal infections. This study aimed to develop and optimize VRC-loaded microemulsion (ME) polymer gels (Carbopol^®-based) for cutaneous delivery. Selected formulations also contained menthol (2%) as a penetration enhancer and potential synergistic antifungal agent. Methods: A comprehensive screening was performed using pseudoternary phase diagrams to identify stable oil/surfactant/co-surfactant/water systems. Selected MEs were prepared with triacetin, Etocas™ 35, and Transcutol^®, then gelled with Carbopol^®. Formulations were characterized for pH, droplet size, polydispersity index (PDI), and viscosity. In vitro VRC release was assessed using diffusion cells, while ex vivo permeation and skin deposition studies were conducted on full-thickness human skin. Rheological behavior (flow curves, yield stress) and texture (spreadability) were evaluated. Antifungal activity was tested against standard strain of Candida albicans and clinical isolates including a fluconazole-resistant strain. Results: The optimized ME (pH ≈ 5.2; droplet size ≈ 2.8 nm) was clear and stable with both VRC and menthol. Gelation produced non-Newtonian, shear-thinning hydrogels with low thixotropy, favorable for topical application. In ex vivo studies, performed with human skin, both VRC-loaded gels deposited the drug in the epidermis and dermis, with no detectable amounts in the receptor phase after 24 h, indicating retention within the skin. Menthol increased VRC deposition. Antifungal testing showed that VRC-containing gels produced large inhibition zones against C. albicans, including the resistant isolate. The VRC–menthol gel exhibited significantly greater inhibition zones than the VRC-only gel, confirming synergistic activity. Conclusions: ME-based hydrogels effectively delivered VRC into the skin. Menthol enhanced drug deposition and demonstrated synergistic antifungal activity with voriconazole. Full article

Keratinocytes are the primary cells of the epidermis layer in our skin. They play a crucial role in maintaining skin health, responding to injuries, and counteracting disease progression. Understanding their behaviour is essential for advancing wound healing therapies, improving outcomes in regenerative medicine, and developing numerical models that accurately mimic skin deformation. To create physically representative models, it is essential to evaluate the nuanced ways in which keratinocytes deform, interact, and respond to mechanical and biochemical signals. This has prompted researchers to investigate various computational methods that capture these dynamics effectively. This review summarises the main mathematical and biomechanical modelling techniques (with particular focus on the literature published since 2010). It includes reaction–diffusion frameworks, finite element analysis, viscoelastic models, stochastic simulations, and agent-based approaches. We also highlight how machine learning is being integrated to accelerate model calibration, improve image-based analyses, and enhance predictive simulations. While these models have significantly improved our understanding of keratinocyte function, many approaches rely on idealised assumptions. These may be two-dimensional unicellular analysis, simplistic material properties, or uncoupled analyses between mechanical and biochemical factors. We discuss the need for multiscale, integrative modelling frameworks that bridge these computational and experimental approaches. A more holistic representation of keratinocyte behaviour could enhance the development of personalised therapies, improve disease modelling, and refine bioengineered skin substitutes for clinical applications. Full article

A diverse array of soil microorganisms exhibit plant growth-promoting (PGP) traits, many of which enhance root growth and development. These microorganisms include various taxa of bacteria, fungi, microalgae and yeasts—some of which are currently used in biofertilizers and biostimulant formulations. Recent studies have begun to unravel the complex communication between plant roots and beneficial microorganisms, revealing mechanisms that modulate root nitrogen (N) uptake beyond atmospheric N₂ fixation pathways. Root N uptake is tightly regulated by plants through multiple mechanisms. These include transcriptional and post-transcriptional control of plasma membrane-localized N transporters in the epidermis, endodermis, and xylem parenchyma. Additionally, N uptake efficiency is influenced by vacuolar N storage, assimilation of inorganic N into organic compounds, and the maintenance of electrochemical gradients across root cell membranes. Many of these processes are modulated by microbial signals. This review synthesizes current knowledge on how soil microorganisms influence root N uptake, with a focus on signaling molecules released by soil beneficial microbes. These signals include phytohormones, volatile organic compounds (VOCs), and various low-molecular-weight organic compounds that affect transporter expression, root architecture, and cellular homeostasis. Special attention is paid to the molecular and physiological pathways through which these microbial signals enhance plant N acquisition and overall nutrient use efficiency. Full article