Search Results (83)

Psoriasis is a chronic inflammatory skin disease marked by abnormal keratinocyte proliferation and immune dysregulation. The vitamin D receptor (VDR) plays a crucial role in regulating skin cell growth and immune responses, but its expression in psoriatic skin and modulation by treatment remain unclear. This study aimed to analyze VDR mRNA expression in psoriatic skin tissue before and after etanercept therapy using RNAscope, an RNA in situ hybridization technique that, to the best of our knowledge, has not previously been applied in psoriasis research. Two bio-naïve adult patients with moderate to severe plaque psoriasis received etanercept (50 mg weekly) for 12 weeks. Skin biopsies from lesional and perilesional areas were collected at baseline and post-treatment. VDR expression was assessed in different epidermal layers and the dermis using a semi-quantitative scoring system. In one patient, a statistically significant decrease in VDR expression was observed in the perilesional dermis after treatment (p < 0.001), though this preliminary finding warrants careful interpretation given the very limited cohort size. Both patients exhibited a non-significant trend toward increased VDR expression in the lesional epidermis post-treatment. These preliminary findings suggest that etanercept may modulate VDR expression in psoriatic skin, but individual variability and the small sample size preclude definitive conclusions. The study primarily demonstrates the feasibility of using RNAscope for VDR analysis in patients with psoriasis, an approach that may be novel in this context, and underscores the need for larger investigations to confirm these preliminary findings and further clarify the role of VDR in disease pathogenesis and treatment response. Full article

Aging, marked by a decline in cellular function and increased risk of diseases, involves the accumulation of senescent cells. This study aims to develop and characterize 3D senescent skin models to understand cellular senescence mechanisms’ implications in cutaneous aging. Normal human epidermal keratinocytes (NHEKs) were cultured from early to late passages (p2 to p7) to induce replicative senescence or sourced from both young and aged donors to reconstruct 3D models. Histological analyses assessed tissue morphology and integrity, while permeability assays evaluated epidermal barrier function. Analyses using immunostaining, RT-PCR, Affymetrix™ GeneChip™ Microarrays identified key markers of cellular senescence, epidermal homeostasis, and other related processes. Results showed that NHEKs at p5 and beyond, and those from aged donors, exhibited significant morphological disruptions, decreased expression of differentiation-associated genes, and impaired barrier function. Increased p16ink4a-positive cells indicated enhanced senescence. Transcriptome analysis revealed significant changes in keratinocyte differentiation, cell–cell interaction, cell cycle regulation, extracellular matrix homeostasis, and inflammation. These findings underscore the relevance of addressing cellular senescence for enhancing skin health and promoting skin longevity. These 3D senescent skin models, validated by consistent results from both passage-induced senescence and aged donor keratinocytes, are valuable for understanding skin aging and developing anti-aging treatments, positioning them as essential tools in the pursuit of skin longevity-focused innovations. Full article

The novel plant hormone strigolactones (SL) are involved significantly in plant growth and development. Its key members SMXL6, 7, 8 can modulate SL signal reception and response negatively and can regulate plant branching remarkably. There are relatively scarce studies of cotton SMXL gene family, and this study was carried out to clarify the role of GbSMXL8 in cotton fiber development. Phylogenetic analysis identified 48 cotton SMXL genes, which were divided into SMXL-I (SMXL 1, 2), SMXL-II (SMXL 3) and SMXL-III (SMXL6, 7, 8) groups. The results of the cis-element analysis indicated that the SMXL gene could respond to hormones and the environment to modulate cotton growth process. A candidate gene GbSMXL8 was screened out based on the expression difference in extreme varieties of Gossypium barbadense. Tissue-specific analysis indicated that GbSMXL8 was mainly expressed in roots, 20D, 25D, and 35D and was involved in SL signaling pathways. In vitro ovule culture experiments showed that exogenous SLs (GR24) could promote the fiber elongation of G. barbadense, and GbSMXL8 expression was increased after GR24 treatment, indicating that GbSMXL8 was specifically responsive to GR24 in regulating fiber growth. GbSMXL8 knockout resulted in creased length and number of epidermal hairs and the length of fiber, indicating the interference role of GbSMXL8 gene with the development of cotton fiber. The GbSMXL8 transgenic plant was detected with a higher chlorophyll content and photosynthetic rate than those of the control plant, producing a direct impact on plant growth, yield, and biomass accumulation. GbSMXL8 gene knockout could increase plant height, accelerate growth rate, and lengthen fiber length. Intervening GbSMXL8 may mediate cotton growth, plant type formation and fiber elongation. In conclusion, the present study uncovers the function of GbSMXL8-mediated SL signal in cotton, providing theoretical insight for future breeding of new cotton varieties. Full article

Background: Within the solar ultraviolet (UV) spectrum, ultraviolet A rays (UVA, 320–400 nm), although less energetic than ultraviolet B rays (UVB, 280–320 nm), constitute at least 95% of solar UV radiation that penetrates deep into the skin The UV rays are associated with both epidermal and dermal damage resulting from the generation of reactive oxygen species (ROS). Among them, the longest UVA wavelengths (UVA1, 340–400 nm) can represent up to 75% of the total UV energy. Therefore, UVA radiation is linked to various acute and chronic conditions, including increased skin pigmentation and photoaging. Despite many advances in the skin photoprotection category, there is still a growing demand for natural daily photoprotection active ingredients that offer broad protection against skin damage caused by UVA exposure. In our quest to discover new, disruptive, next generation of photoprotective ingredients, we were drawn to pomegranate, based on its diverse polyphenolic profile. We investigated the pericarp of the fruit, so far considered as byproducts of the pomegranate supply chain, to design a novel patented extract “POMAOX” with a desired spectrum of phenolic components comprising of αβ-punicalagins, αβ-punicalins and ellagic acid. Methods: Antioxidant properties of POMAOX were measured using in-tubo standard tests capable of revealing a battery of radical oxygen species (ROS): peroxyl radical (ORAC), singlet oxygen (SOAC), superoxide anion (SORAC), peroxynitrite (NORAC), and hydroxyl radical (HORAC). In vitro, confirmation of antioxidant properties was first performed by evaluating protection against UVA-induced lipid peroxidation in human dermal fibroblasts (HDF), via the release of 8 iso-prostanes. The protection offered by POMAOX was further validated in a 3D in vitro reconstructed T-Skin^TM model, by analyzing tissue viability/morphology and measuring the release of Matrix Metallopeptidase 1 (MMP-1) & pro-inflammatory mediators (IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNF-α) after UVA1 exposure. Results: POMAOX displayed strong antioxidant activity against peroxynitrite (NORAC) at 1.0–3.0 ppm, comparable to the reference vitaminC, as well as singlet oxygen (SOAC) at 220 ppm, and superoxide radicals with a SORAC value of 500 ppm. Additionally, POMAOX demonstrated strong photoprotection benefit at 0.001% concentration, offering up to 74% protection against UVA-induced lipid peroxidation on HDF, in a similar range as the positive reference, Vitamin E at 0.002% (50 µM), and with higher efficacy than ellagic acid alone at 5 µM. Moreover, our pomegranate-derived extract delivered photoprotection at 0.001%, mitigating dermal damages induced by UVA1, through inhibition of MMP-1 and significant inhibition of pro-inflammatory mediators release (including IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNFα) on an in vitro reconstructed full-thickness human skin model with a similar level of protection to that of Vitamin C tested at 0.035% (200 µM). Conclusions: Overall, the novel pomegranate-derived extract “POMAOX” significantly reduced the impact of UVA on human skin, due to its broad-spectrum antioxidant profile. These findings suggest that POMAOX could offer enhanced protection against the detrimental effects of UV exposure, addressing the growing consumer demand for strong photoprotection with skincare benefits. Full article

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, arises from skeletal muscle cells that fail to differentiate terminally. Two subgroups of RMS, fusion-positive and fusion-negative RMS (FPRMS and FNRMS, respectively), are characterized by the presence or absence of the PAX3/7-FOXO1 fusion gene. RMSs frequently exhibit increased expression of human epidermal growth factor receptor-2 (HER2). Trastuzumab is a humanized monoclonal antibody targeting HER2, and its potential role in RMS treatment remains to be elucidated. Syndecan-4 (SDC4) is a heparan sulfate proteoglycan (HSPG) affecting myogenesis via Rac1-mediated actin remodeling. Previously, we demonstrated that the SDC4 gene is amplified in 28% of human FNRMS samples, associated with high mRNA expression, suggesting a tumor driver role. In this study, after analyzing the copy numbers and mRNA expressions of other HSPGs in human RMS samples, we found that in addition to SDC4, syndecan-1, syndecan-2, and glypican-1 were also amplified and highly expressed in FNRMS. In RD (human FNRMS) cells, elevated SDC4 expression was accompanied by low levels of phospho-Ser179 of SDC4, leading to high Rac1-GTP activity. Notably, this high SDC4 expression in RD cells decreased following trastuzumab treatment. Trastuzumab decreased the levels of G1/S checkpoint regulators cyclin E and cyclin D1 and reduced the cell number; however, it also downregulated the cyclin-dependent kinase inhibitor p21. The level of MyoD, a transcription factor essential for RMS cell survival, also decreased following trastuzumab administration. Our findings contribute to the understanding of the role of SDC4 in FNRMS. Since HER2 is expressed in about half of RMSs, the trastuzumab-mediated changes observed here may have therapeutic implications. Full article

Background/Objectives: Vacuolar (H⁺)-ATPases (V-ATPases) are crucial in several significant biological processes, including intracellular transport, endocytosis, autophagy and protein degradation. However, their role in the growth and development of insects remains largely unknown. This study aimed to explore the molecular and functional properties of V-ATPases in Locusta migratoria. Methods: LmV-ATPase genes were identified based on the locust transcriptome database and bioinformatics analysis. Quantitative reverse-transcription polymerase chain reaction was used to assess the relative expression of LmV-ATPases in different tissues and developmental stages. RNA interference combined with hematoxylin–eosin staining and transmission electron microscopy was used to explore the functions of LmV-ATPases. Results: Ten V-ATPase genes were identified in L. migratoria and were named LmV-ATPase A, B, C, D, E, F, G, c″, d and e, respectively. These genes were highly expressed in the head, integument, gastric caecum, midgut, hindgut, fat body, trachea and ovary. The transcripts of LmV-ATPases were expressed in the developmental stages examined (from the 3rd to 5th instar nymphs). The injection of double-stranded RNA (dsRNA) against each LmV-ATPase induced high silencing efficiency in the 3rd instar nymphs. Knockdown of LmV-ATPases resulted in lethal phenotypes, with visible defects of the wing and cuticle. We further demonstrated that the deformation was caused by the defects of epidermal cells and fewer new cuticles. Conclusions: These findings suggest that LmV-ATPases are required for the wing and cuticle development of L. migratoria, which could be potential targets for the control of locusts. Full article

Skin ulcers are open wounds on the skin characterized by the loss of epidermal tissue. Skin ulcers can be acute or chronic, with chronic ulcers persisting for over six weeks and often being difficult to heal. Treating chronic wounds involves periodic visual inspections to control infection and maintain moisture balance, with edge and size analysis used to track wound evolution. This condition mostly affects individuals over 65 years old and is often associated with chronic conditions such as diabetes, vascular issues, heart diseases, and obesity. Early detection, assessment, and treatment are crucial for recovery. This study introduces a method for automatically detecting and segmenting skin ulcers using a Convolutional Neural Network and two-dimensional images. Additionally, a three-dimensional image analysis is employed to extract key clinical parameters for patient assessment. The developed system aims to equip specialists and healthcare providers with an objective tool for assessing and monitoring skin ulcers. An interactive graphical interface, implemented in Unity3D, allows healthcare operators to interact with the system and visualize the extracted parameters of the ulcer. This approach seeks to address the need for precise and efficient monitoring tools in managing chronic wounds, providing a significant advancement in the field by automating and improving the accuracy of ulcer assessment. Full article

The involvement of stress ethylene in early chilling injury (CI) symptom development of mature-green (MG) banana fruit was examined using the ethylene action inhibitor, 1-methyclopropene (1-MCP). MG banana fruit pretreated with 0 or 50 μg L⁻¹ 1-MCP were stored at two chilling temperatures, 5 °C or 10 °C, for 0, 1, 12, or 72 h (different CI stresses), then transferred to 20 °C (rewarming) for 2 d. Irreversible CI symptoms that developed during 72 h storage at 5 or 10 °C included vascular browning and epidermal color parameters (L*, chroma, and hue angle). Some CI symptoms drastically intensified during exposure to 5 or 10 °C for 72 h, even being exacerbated after rewarming. Fruit in the other treatments suffered milder CI, and the recovery response progressed from slight and reversible to severe and irreversible with longer durations of exposure to lower temperatures. The effect of 1-MCP pretreatment was to attenuate the effect of chilling in terms of the CI symptom development (i.e., the browning of sub-epidermal tissues and the increasing of electrolyte efflux) and to promote recovery after rewarming, especially for the fruit stored at 5 °C, indicating the potential involvement of ethylene in membrane structural alterations under CI stress. Full article

Resolvin D5 (RvD5) is a lipid mediator that has been reported to present anti-inflammatory and pro-resolution properties. Evidence also supports its capability to enhance reactive oxygen species (ROS) production during bacterial infections, which would be detrimental in diseases driven by ROS. The biological activity of RvD5 and mechanisms against UVB irradiation skin pathology have not been investigated so far. Female hairless mice were treated intraperitoneally with RvD5 before UVB stimulus. RvD5 reduced skin edema in a dose-dependent manner as well as oxidative stress by increasing antioxidants (endogenous tissue antioxidant scavenging of cationic radical, iron reduction, catalase activity and reduced glutathione levels) and decreasing pro-oxidants (superoxide anion and lipid peroxidation). RvD5 antioxidant activity was accompanied by enhancement of Nrf2, HO-1 and NQO1 mRNA expression. RvD5 reduced the production of IL-1β, TNF-α, TGF-β, and IL-10. RvD5 also reduced the inflammatory cell counts, including mast cells and neutrophils/macrophages. The reduction of oxidative stress and inflammation resulted in diminished matrix metalloproteinase 9 activity, collagen degradation, epidermal thickening and sunburn cell development. Therefore, this study demonstrates, to our knowledge, the first body of evidence that RvD5 can be used to treat UVB skin pathology and unveils, at least in part, its mechanisms of action. Full article

Chronic skin wounds are estimated to affect 6.5 million patients in the US, at a cost of over USD 25 billion. Efforts to prevent and/or treat such wounds will result in reduced morbidity and economic losses. This project is focused on the role of vitamin D signaling in the epidermis in the control of stem cell (SC) activation and function during the initial response to the wounding of the skin, a response that, if defective, contributes to poor wound healing or cancer. In this review, I first describe the anatomy of the skin, focusing first on the epidermis, describing the different cell layers which in a spatial way also represent the differentiation process of the interfollicular epidermis (IFE) as it undergoes continuous regeneration. I then describe the other components of the skin, particularly the hair follicle (HF), which undergoes a cyclic pattern of regeneration. Adult SCs residing in these regenerative tissues play essential roles in the maintenance of these tissues. However, when the skin is wounded, the progeny of SCs from all regions of the HF and IFE contribute to the healing process by changing their initial cell fate to take on an epithelial genotype/phenotype to heal the wound. Although earlier lineage tracing studies helped to define the contributions SCs from the different niches made to wound healing, scRNAseq studies have demonstrated a considerably more nuanced picture. The role of vitamin D signaling will be introduced by reviewing the unique role played by the epidermal keratinocyte first in producing vitamin D and then in metabolizing it into its active form 1,25(OH)2D. 1,25(OH)2D is the principal ligand for the vitamin D receptor (VDR), a transcription factor that helps to mediate the genomic changes in the stem cells in their response to wounding. In these actions, the VDR is regulated by coregulators, of which the steroid receptor coactivator complexes SRC 2 and 3 and the mediator complex (MED) play essential roles. The VDR generally acts in association with other transcription factors such as p63 and β-catenin that can colocalize with the VDR in the genes it regulates. Although much remains to be understood, the role of the VDR in the stem cell response to wounding is clearly essential and quite different from its classic roles in regulating calcium metabolism, although calcium is essential for the actions of vitamin D signaling in the skin. Full article

In this study, the potential of silk fibroin biomaterials for enhancing wound healing is explored, focusing on their integration into a human 3D ex vivo wound model derived from abdominoplasties. For this purpose, cast silk fibroin membranes and electrospun nonwoven matrices from Bombyx mori silk cocoons were compared to untreated controls over 20 days. Keratinocyte behavior and wound healing were analyzed qualitatively and quantitatively by histomorphometric and immune histochemical methods (HE, Ki67, TUNEL). Findings reveal rapid keratinocyte proliferation on both silk fibroin membrane and nonwoven matrices, along with enhanced infiltration in the matrix, suggesting improved early wound closure. Silk fibroin membranes exhibited a significantly improved early regeneration, followed by nonwoven matrices (p < 0.05) compared to untreated wounds, resulting in the formation of multi-layered epidermal structures with complete regeneration. Overall, the materials demonstrated excellent biocompatibility, supporting cell activity with no signs of increased apoptosis or early degradation. These results underscore silk fibroin’s potential in clinical wound care, particularly in tissue integration and re-epithelialization, offering valuable insights for advanced and—as a result of the electrospinning technique—individual wound care development. Furthermore, the use of an ex vivo wound model appears to be a viable option for pre-clinical testing. Full article

Skin yellowness is a hallmark of dull or unhealthy skin, particularly among Asians. Previous research has indicated a link between skin glycation and skin yellowness. However, the specific glycated chemicals contributing to yellowish skin appearance have not been identified yet. Using HPLC-PDA-HRMS coupled with native and artificially glycated human epidermal explant skin, we identified intensely yellow colored glycated chromophores “(1R, 8aR) and (1S, 8aR)-4-(2-furyl)-7-[(2-furyl)-methylidene]-2-hydroxy-2H,7H,8AH-pyrano-[2,3-B]-pyran-3-one” (abbreviated as AGEY) from human skin samples for the first time. The abundance of AGEY was strongly correlated with skin yellowness in the multiple skin explant tissues. We further confirmed the presence of AGEY in cultured human keratinocytes and 3D reconstructed human epidermal (RHE) models. Additionally, we demonstrated that a combination of four cosmetic compounds with anti-glycation properties can inhibit the formation of AGEY and reduce yellowness in the RHE models. In conclusion, we have identified specific advanced glycation end products with an intense yellow color, namely AGEY, in human skin tissues for the first time. The series of study results highlighted the significant contribution of AGEY to the yellow appearance of the skin. Furthermore, we have identified a potential cosmetic solution to mitigate AGEY formation, leading to a reduction in yellowness in the in vitro RHE models. Full article

One of the primary complications in generating physiologically representative skin tissue is the inability to integrate vasculature into the system, which has been shown to promote the proliferation of basal keratinocytes and consequent keratinocyte differentiation, and is necessary for mimicking representative barrier function in the skin and physiological transport properties. We created a 3D vascularized human skin equivalent (VHSE) with a dermal and epidermal layer, and compared keratinocyte differentiation (immunomarker staining), epidermal thickness (H&E staining), and barrier function (transepithelial electrical resistance (TEER) and dextran permeability) to a static, organotypic avascular HSE (AHSE). The VHSE had a significantly thicker epidermal layer and increased resistance, both an indication of increased barrier function, compared to the AHSE. The inclusion of keratin in our collagen hydrogel extracellular matrix (ECM) increased keratinocyte differentiation and barrier function, indicated by greater resistance and decreased permeability. Surprisingly, however, endothelial cells grown in a collagen/keratin extracellular environment showed increased cell growth and decreased vascular permeability, indicating a more confluent and tighter vessel compared to those grown in a pure collagen environment. The development of a novel VHSE, which incorporated physiological vasculature and a unique collagen/keratin ECM, improved barrier function, vessel development, and skin structure compared to a static AHSE model. Full article

The dermal–epidermal junction (DEJ), located between the dermal–epidermal layers in human skin tissue, plays a significant role in its function. However, the limitations of biomaterial properties and microstructure fabrication methods mean that most current tissue engineered skin models do not consider the existence of DEJ. In this study, a nanofiber membrane that simulates the fluctuating structure of skin DEJ was prepared by the composite molding process. Electrospinning is a technique for the production of nanofibers, which can customize the physical and biological properties of biomaterials. At present, electrospinning technology is widely used in the simulation of customized natural skin DEJ. In this study, four different concentration ratios of poly (lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanofiber membranes were prepared based on electrospinning technology. We selected a 15%PLGA + 5%PCL nanofiber membrane with mechanical properties, dimensional stability, hydrophilicity, and biocompatibility after physical properties and biological characterization. Then, the array-based microstructure model was prepared by three-dimensional (3D) printing. Subsequently, the microstructure was created on a 15%PLGA + 5%PCL membrane by the micro-imprinting process. Finally, the cell proliferation and live/dead tests of keratinocytes (HaCaTs) and fibroblasts (HSFs) were measured on the microstructural membrane and flat membrane. The results showed that 15%PLGA + 5%PCL microstructure membrane was more beneficial to promote the adhesion and proliferation of HaCaTs and HSFs than a flat membrane. Full article

Goose is one of the most economically valuable poultry species and has a distinct appearance due to its possession of a knob. A knob is a hallmark of sexual maturity in goose (Anser cygnoides) and plays crucial roles in artificial selection, health status, social signaling, and body temperature regulation. However, the genetic mechanisms influencing the growth and development of goose knobs remain completely unclear. In this study, histomorphological and transcriptomic analyses of goose knobs in D70, D120, and D300 Yangzhou geese revealed differential changes in tissue morphology during the growth and development of goose knobs and the key core genes that regulate goose knob traits. Observation of tissue sections revealed that as age increased, the thickness of the knob epidermis, cuticle, and spinous cells gradually decreased. Additionally, fat cells in the dermis and subcutaneous connective tissue transitioned from loose to dense. Transcriptome sequencing results, analyzed through differential expression, Weighted Gene Co-expression Network Analysis (WGCNA), and pattern expression analysis methods, showed D70-vs.-D120 (up-regulated: 192; down-regulated: 423), D70-vs.-D300 (up-regulated: 1394; down-regulated: 1893), and D120-vs.-D300 (up-regulated: 1017; down-regulated: 1324). A total of 6243 differentially expressed genes (DEGs) were identified, indicating varied expression levels across the three groups in the knob tissues of D70, D120, and D300 Yangzhou geese. These DEGs are significantly enriched in biological processes (BP) such as skin morphogenesis, the regulation of keratinocyte proliferation, and epidermal cell differentiation. Furthermore, they demonstrate enrichment in pathways related to goose knob development, including ECM–receptor interaction, NF-kappa B, and PPAR signaling. Through pattern expression analysis, three gene expression clusters related to goose knob traits were identified. The joint analysis of candidate genes associated with goose knob development and WGCNA led to the identification of key core genes influencing goose knob development. These core genes comprise WNT4, WNT10A, TCF7L2, GATA3, ADRA2A, CASP3, SFN, KDF1, ERRFI1, SPRY1, and EVPL. In summary, this study provides a reference for understanding the molecular mechanisms of goose knob growth and development and provides effective ideas and methods for the genetic improvement of goose knob traits. Full article