Epidermal Layer Research Articles

Paxbp1 Is Indispensable for the Maintenance of Epidermal Homeostasis

The mammalian epidermis is a structurally complex tissue that serves critical barrier functions, safeguarding the organism from the external milieu. The development of the epidermis is governed by sophisticated regulatory processes. However, the precise mechanism maintaining epidermal homeostasis remains incompletely elucidated. Recent studies have identified Paxbp1, an evolutionarily conserved protein, as being involved in the developmental regulation of various cells, tissues, and organs. Nonetheless, its role in skin development has not been explored. Here, we report that the targeted deletion of Paxbp1 in epidermal keratinocytes mediated by Keratin14-Cre leads to severe disruption in skin architecture. Mice deficient in Paxbp1 exhibited a substantially reduced epidermal thickness and pronounced separation at the dermo-epidermal junction upon birth. Mechanistically, we demonstrate that the absence of Paxbp1 hinders cellular proliferation, marked by a halt in cell cycle transition, suppressed gene expression of proliferation, and a compromised DNA replication pathway in basal keratinocytes, resulting in the thinning of the skin epidermis. Moreover, molecules and pathways associated with hemidesmosome assembly were impaired in Paxbp1-deficient keratinocytes, culminating in the detachment of the skin epidermal layer. Therefore, our study highlights an indispensable role of Paxbp1 in the maintenance of epidermal homeostasis.

Nanozyme microspheres with structural color-coding labels for synergistic therapy of psoriasis

Psoriasis is an immune system-mediated skin disease identified by the appearance of erythematous as a central symptom. As a recurrent and chronic inflammatory disease, psoriasis is influenced by both genetic and environmental factors and is known to be with no effective cure. Considering a multifaceted etiology of psoriasis, synergistic therapy exhibits great benefits over monotherapy, which becomes common for the treatment of various diseases. Herein, we present the nanozyme microspheres with structural color-coding labels for synergistic therapy of psoriasis. In particular, microsphere hydrogel is fabricated by the edible hydroxypropyl cellulose (HPC), which can generate a photonic liquid crystalline mesophase under lyotropic conditions in solution. Through adjustment of hydrogel components, microspheres endow with different functions, including moisturizing (paraffin), cfDNA scavenging (chitosan), and anti-inflammation (cerium oxide nanozyme). To improve patient convenience, hydrogel drops with different properties are tailored with different vivid structural colors by exploiting the lyotropic behavior of HPC. Of particular note, both in vitro and in vivo experiments have demonstrated the significant therapeutic effects of the encoded structural color microspheres. Green moisturizing microspheres facilitate to relieve dry, flaky skin patches; blue cfDNA scavenging and red anti-inflammatory microspheres significantly reduce skin inflammation. More importantly, combination therapy with encoded microspheres exerted the synergistic effects, including the increased body weight, thicker epidermal layer, and reduced immune activation. Overall, this synergistic treatment offers a promising platform for personalized management of psoriasis and various inflammatory skin diseases.

Comparison of facial skin ageing in healthy Asian and Caucasian females quantified by in vivo line-field confocal optical coherence tomography 3D imaging.

Quantitative biomarkers of facial skin aging were investigated in 109 healthy Asian female volunteers, aged 20 to 70 years. In vivo 3D Line-field Confocal Optical Coherence Tomography (LC-OCT) imaging, enhanced by Artificial Intelligence (AI)-based quantification algorithms, was utilized to compute various metrics, including stratum corneum thickness (SC), viable epidermal (VE) thickness, and Dermal-Epidermal Junction (DEJ) undulation along with cellular metrics for the temple, cheekbone, and mandible. Comparison with data from a cohort of healthy Caucasian volunteers revealed similarities in the variations of stratum corneum and viable epidermis layers, as well as cellular shape and size with age in both ethnic groups. However, specific findings emerged, such as larger, more heterogeneous nuclei in both layers, demonstrated by an increase in nuclei volume and their standard deviation, and increased network atypia, all showing significant age-related variations. Caucasian females exhibited a flatter and more homogeneous epidermis, evidenced by a decreased standard deviation of the number of layers, and a less dense cellular network with fewer cells per layer, indicated by a decrease in cell surface density. Ethnicity-wise comparisons highlighted distinct biological features specific to each population. Asian individuals showed significantly higher DEJ undulation, higher compactness, and lower cell network atypia compared to their Caucasian counterparts across age groups. Differences in stratum corneum and viable epidermal thickness on the cheekbone were also significant. LC-OCT 3D imaging provides valuable insights into the aging process in different populations and underscores inherent biological differences between Caucasian and Asian female volunteers.

The Skin Histopathology of Pro- and Parabiotics in a Mouse Model of Atopic Dermatitis.

As it has been revealed that the activation of human immune cells through the activity of intestinal microorganisms such as pro- and prebiotics plays a vital role, controlling the proliferation of beneficial bacteria and suppressing harmful bacteria in the intestine has become essential. The importance of probiotics, especially for skin health and the immune system, has led to the emergence of products in various forms, including probiotics, prebiotics, and parabiotics. In particular, atopic dermatitis (AD) produces hypersensitive immunosuppressive substances by promoting the differentiation and activity of immune regulatory T cells. As a result, it has been in the Th1 and Th2 immune balance through a mechanism that suppresses skin inflammation or allergic immune responses caused by bacteria. Furthermore, an immune mechanism has recently emerged that simultaneously controls the expression of IL-17 produced by Th17. Therefore, the anti-atopic effect was investigated by administering doses of anti-atopic candidate substances (Lactobacilus sakei CVL-001, Lactobacilus casei MCL, and Lactobacilus sakei CVL-001 Lactobacilus casei MCL mixed at a ratio of 4:3) in an atopy model using 2,4-dinitrochlorobenzene and observing symptom changes for 2 weeks to confirm the effect of pro-, para-, and mixed biotics on AD. First, the body weight and feed intake of the experimental animals were investigated, and total IgG and IgM were confirmed through blood biochemical tests. Afterward, histopathological staining was performed using H&E staining, Toluidine blue staining, Filaggrin staining, and CD8 antibody staining. In the treatment group, the hyperproliferation of the epidermal layer, the inflammatory cell infiltration of the dermal layer, the expression of CD8, the expression of filaggrin, and the secretion of mast cells were confirmed to be significantly reduced. Lastly, small intestine villi were observed through a scanning microscope, and scoring evaluation was performed through skin damage. Through these results, it was confirmed that AD was reduced when treated with pro-, para-, and mixed biotics containing probiotics and parabiotics.

Graphene powders as new contact nanopesticides: Revealing key parameters on their insecticidal activity for stored product insects

The overuse and reliance on pesticides has caused insects to develop resistance with global concerns. To address this problem extensive research is directed to find new and sustainable alternatives using chemical-free and resistance-free solutions for pest control. This paper presents a comprehensive investigation of the insecticidal properties of several types of industrially produced graphene powder materials such as graphene and graphene oxide (GO) with micro- and nano size and different structural and chemical properties as new contact nanopesticides against three major stored grain insects: the rice weevil Sitophilus oryzae (L.), the lesser grain borer, Rhyzopertha dominica (F.)˙ and the larger grain borer, Prostephanus truncatus Horn. Bioassays were performed using different concentrations, i.e., 0, 100, 500 and 1000 ppm of graphene powders on the mortality of selected adult insects recorded after 3, 7, 14, and 21 days of exposure and progeny production after 65 days. Results showed that graphene oxide (GO) has no insecticidal efficacy while graphene powders with nano-size particles showed significantly enhanced insecticidal performance compared to micron-size graphene powders. The observed insecticidal effects are explained by the higher probability that nano-sized graphene particles adhere on the insect body compared to large particles. The mortality is proposed as the result of physical mode of action of attached graphene nanoparticles causing stronger interruption of the protective cuticle layer, gas respiratory functions and faster mortality. The findings of this study revealed that it is important to select graphene materials with optimal structural and interfacial properties to achieve the highest insecticidal performance in potential development of a new generation of sustainable insecticides.

Genome-Wide Association Study of Cuticle and Lipid Droplet Properties of Cucumber (Cucumis sativus L.) Fruit.

The fruit surface is a critical first line of defense against environmental stress. Overlaying the fruit epidermis is the cuticle, comprising a matrix of cutin monomers and waxes that provides protection and mechanical support throughout development. The epidermal layer of the cucumber (Cucumis sativus L.) fruit also contains prominent lipid droplets, which have recently been recognized as dynamic organelles involved in lipid storage and metabolism, stress response, and the accumulation of specialized metabolites. Our objective was to genetically characterize natural variations for traits associated with the cuticle and lipid droplets in cucumber fruit. Phenotypic characterization and genome-wide association studies (GWAS) were performed using a resequenced cucumber core collection accounting for >96% of the allelic diversity present in the U.S. National Plant Germplasm System collection. The collection was grown in the field, and fruit were harvested at 16-20 days post-anthesis, an age when the cuticle thickness and the number and size of lipid droplets have stabilized. Fresh fruit tissue sections were prepared to measure cuticle thickness and lipid droplet size and number. The collection showed extensive variation for the measured traits. GWAS identified several QTLs corresponding with genes previously implicated in cuticle or lipid biosynthesis, including the transcription factor SHINE1/WIN1, as well as suggesting new candidate genes, including a potential lipid-transfer domain containing protein found in association with isolated lipid droplets.

Histological comparison of shark dermis across various ecomorphologies.

The integument plays essential roles in the structural support, protection, and hydrodynamic capability among fishes. Most research on shark skin has focused on the external epidermal layer, while the larger dermis anchoring the dermal denticles has been mostly ignored. Shark dermis is composed of two layers, the upper stratum laxum and the lower stratum compactum, holding supportive collagen and elastic fibers. There may be morphological and compositional differences in the dermis across various species of sharks that could relate to their different swimming modes and ecologies. The goal of this study was to characterize and describe the dermis among three shark species, Ginglymostoma cirratum, Sphyrna mokarran, and Isurus oxyrinchus, each representing a different swimming mode. Histological characterizations were performed at 16 locations along the body of each shark; variables such as dermal thickness, abundance of collagen and elastic fibers, and fiber size were quantified. Results showed G. cirratum has the thickest skin overall, and the largest fiber size for both collagen and elastic fibers, with overall patterns of increased amounts of collagen fibers and decreased amount of elastic fibers. At the opposite end of the spectrum, I. oxyrinchus showed the thinnest dermis along the flank region, with overall patterns of increased elastic fibers and decreased collagen fibers. These findings may challenge our original assumptions of a rigid body in fast moving sharks and a more flexible body in slower moving sharks and highlight the diversity of the shark integument.

Morphological and anatomical studies in Nigella sativa L. (Ranunculaceae)

This research delves into the morphological and anatomical intricacies of Nigella sativa L. (Ranunculaceae), commonly known as black cumin, through meticulous examination of various accessions collected from diverse geographical regions in India. Morphological studies revealed distinct characteristics such as the linear to lanceolate alternate leaves, black capsule fruit housing seeds, and growth parameters including germination time, maturation period, and yield per plant. Notably, certain accessions exhibited superior attributes in terms of plant height, root length, and seed yield. Anatomical investigations unveiled detailed structures of stems, roots, seeds, and capsules. Stem anatomy exhibited a multi-cornered structure with specific features like uniseriate epidermis with non-glandular trichomes, parenchymatous cortex with chlorenchymatous and sclerenchymatous cells, and distinct vascular bundle arrangements. Root anatomy depicted a circular cross-section with well-defined layers including epidermis, cortex, and xylem with prominent oil droplets. Seed anatomy displayed layers of epidermis, parenchyma, pigmented layer, endosperm, and a central embryo. Moreover, this study identified novel cells in the stem cortex and observed variability in carpel numbers among different accessions. The findings contribute significantly to the understanding of N. sativa morphology and anatomy, shedding light on previously unexplored aspects and emphasizing the need for further investigation into the variability within and among accessions.

Ion transport peptide and ion transport peptide-like regulate ecdysis behavior and water transport during ecdysis in Gryllus bimaculatus

Ion transport peptide (ITP) and ITP-like (ITPLs) are pleiotropic bioactive peptides in insects. Although the contribution of these peptides to ecdysis has been studied, the precise regulatory mechanisms remain poorly understood. Here, we characterized the functions of itp and itpl variants in the two-spotted cricket, Gryllus bimaculatus. Reverse transcription-quantitative PCR and whole-mount in situ hybridization revealed that itp was expressed in the brain and terminal abdominal ganglion, whereas itpl variants were expressed in all ganglia of the central nervous system. Simultaneous knockdown of itp and itpls disrupted ecdysis behavior and water transport from the gut into the hemolymph during molting. Nevertheless, knockdown of itpls without influencing itp expression did not significantly affect ecdysis behavior but caused a reduction in hemolymph mass. Although water transport into the hemolymph is considered necessary for the swelling required to split the old cuticle layers during molting, a rescue experiment by injection of water or cricket Ringer's solution into the hemolymph of knockdown crickets did not recover the normal phenotype. Therefore, we propose that ITP/ITPL control ecdysis behavior probably not by regulating water transport from the gut into the hemolymph in crickets.

Chitosan/gelatin coating loaded with ginger essential oil/β-cyclodextrin inclusion complex on quality and shelf life of blueberries

Blueberries are highly susceptible to fungal pathogens and oxidative deterioration due to their thin epidermal layer, which can be mitigated by applying a natural polymer-based antimicrobial coating to their surface. This study aimed to develop a chitosan/gelatin-based antimicrobial coating utilizing ginger essential oil (GEO) to extend the postharvest quality of blueberries. To ensure GEO's stability within the coating, it was initially encapsulated with β-cyclodextrin (β-CD) using the inclusion complexation technique. The GEO/β-CD inclusion complex (IC) formed rhomboidal shapes with high encapsulation efficiency and small particle sizes. When the optimized GEO/β-CD IC was incorporated into the chitosan/gelatin polymer solution, it significantly increased surface hydrophobicity and free radical scavenging activity, and suppressed the growth of three selected fungi, namely Botrytis cinerea, Penicillium italicum and Alternaria alternaria. The results of postharvest storage quality revealed that blueberry samples coated with CH/Gel-GEO/β-CD IC-5 effectively maintained the quality of blueberries by decreasing weight loss and decay incidence, and regulating anthocyanin and other oxidation-related enzyme activities compared to the control group during 16 days at 25 °C and 40 days at 4 °C storages. In conclusion, it can be stated that CH/Gel-GEO/β-CD composite coating can be a promising technology to address the drawbacks of blueberry preservation.

Changes of epidermal proteins immunolocalization in the corneous layer from embryonic to definitive avian beak

The process of keratinization and cornification in the developing beak has been studied through immunofluorescence and immunogold electron microscopy in chick and zebrafinch embryos. After the curved beak anlagen appears at the tip of the maxillar bone, 5–8 layers of embryonic epidermis are generated from the basal layer of the epidermis. These cells are weakly immunoabeled for IFKs (Intermediate Filament Keratins) and more intensely for scaffoldin, a protein of the EDC (Epidermal Differentiation Complex) involved in the soft keratinization of the embryonic epidermis. Immunolabeling for CBPs (Corneous Beta Proteins) is visible in the transitional embryonic layers that are temporarily generated between the embryonic and definitive beak epidermis. The electron microscope reveals that intermediate layers contain immunolabeled periderm granules for scaffoldin mixed with bundles of corneous material immunolabeled for CBPs. Intense CBPs labeling occurs in the compacting corneous bundles of beta-keratinocytes in the definitive beak while scaffolding labeling disappears. The embryonic epidermis is sloughed before hatching. Sox (Sulfhydryl Oxidase) immunolabeling reveals that the enzyme is almost absent in embryonic layers but is present in transitional and definitive beta-keratinocytes. This indicates the formation of cross-linked disulfide bonds in the definitive corneous layer of the beak. Some calcium precipitation, suggested from von Kossa staining, occurs in the corneous layers only on the 18th day of development in the chick, in preparation for hatching.

Increased nanosphere size in the cuticle layer of Japanese quail egg by mutation in the myostatin gene

Cuticle quality can affect food safety by protecting poultry eggs from bacterial infection in the modern poultry industry. However, genetic factors related to cuticle nanostructure are not much reported due to limited bird models. In the current study, the genome-edited quail targeting myostatin (MSTN) gene was used to investigate the effect of MSTN mutation on the cuticle nanostructure and quality. To analyze nanostructure of the cuticle layer of the MSTN mutant and wild-type (WT) quail eggs, scanning electron microscope (SEM) images was taken. Thickness of the cuticle layer did not differ between the MSTN mutant and WT groups, but the size of the nanospheres in the surface of the cuticle layer was increased by MSTN mutation. In addition, increased size of the nanospheres in the MSTN mutant group was also shown in the upper region of the cross-sectional cuticle layer. Notably, both groups showed similar small-sized nanospheres in the lower region of the cuticle layer and the size was increased as they ascended to the upper region. The data suggested that MSTN mutation increased the size of the nanosphere in the upper region of the cuticle layer at a late phase rather than increasing the size of nanospheres in the lower region of the cuticle layer at an early phase of cuticle formation. However, the number of Escherichia coli attached to the surface did not differ between the two groups indicating no association between nanosphere size and bacterial attachment in quail eggs. The current study demonstrated a new function of the MSTN gene on regulation of cuticle nanostructure, for the first time. These results advanced our knowledge on the association between genetic factors and cuticle nanostructure and can be served as a reference to study the mechanism of cuticle formation in the future study.

Clinical outcomes of hydrofiber foam dressing in the treatment of abrasion wounds: A retrospective study.

Mopeds are a popular mode of transportation in Taiwan, yet collision accidents often lead to abrasion requiring medical attention. While hydrofiber foam dressing (HFD) have proven to help control exudates, reduce the frequency of dressing changes, and preserve more viable tissue, there is currently no established clinical guideline for the treatment of abrasion wounds with dressings. Therefore, the aim of this study was to investigate the clinical outcomes of abrasions treated with hydrofiber foam dressings. A total of 127 patients treated with HFDs between June 2018 and January 2021 were included in this study. Abrasions were categorized into 3 grades: grade I (n = 0) involving the epidermal layer, grade II (n = 89) involving the dermal layer, and grade III (n = 38) involving subcutaneous layer, bone or tendon. Statistical analysis showed that there was a significant difference in healing time (P < 0.001) and the number of outpatient department (OPD) visits (P = 0.013) between grade II and grade III. However, there was no significant difference in the number of dressing pieces used. This study offers a clinical reference for the use of hydrofiber foam dressings in treating different grades of abrasion wounds caused by moped accidents.

A Electron micrograph of the leaf epidermal structure of legumes

Our goal was to find morphological features that can help us identify or describe the stomata ontogeny and epidermal structures. Our team got seeds of two types of leguminous plants—Arachis hypogaea L. groundnuts and Vigna subterranean L. bambaranuts—from the Kano State Agricultural and Rural Development Authority and the Yankaba market in Nassarawa, which is in Kano State. The study specifically evaluated the leaf epidermal studies, stomata development (ontogeny), types of stomata, stomata size, pore length, pore width, and stomata index in both the surfaces of the leaves. We conducted ontogenetic studies using safety razor blades on the epidermal layers. We determined the stomata index by studying the type of stomata, the number of stomata, and the number of epidermal cells. We subjected the obtained data to a one-way analysis of variance. All the studied varieties/species exhibited amphistomatic stomata on both surfaces, with a higher density on the lower surface. In SAMNUT 23, we found the paracytic type of stomata, which is perigynous and has an irregular anticlinal cell wall. In Dandakar, we found the tetracyclic type, which is mesogynous and has a pentagonal epidermal cell shape and a slightly straight anticlinal cell wall. Finally, in Bambara nuts, we found the endocytic type, which is polygonal with a curved anticlinal wall and a mesoperigynous ontogeny.

Effect of critical temperatures on mortality and cuticle composition of Plodia interpunctella larvae: Insights from GC–MS analysis and SEM imaging

The Indian meal moth, Plodia interpunctella Hübner (Lep.: Pyralidae), is a significant global pest of stored products, particularly in temperate regions. This study investigated the impact of various temperatures (25, 50, 55, and 60 °C) over different durations (5, 10, 15 and 20 min) on the mortality and cuticle layer of third instar P. interpunctella larvae. Hexane solvent separated the cuticle layer of 3rd instar larvae treated at critical temperatures; Bis (trimethylsilyl) acetamide and Trimethylsilyl chloride were added for derivatization before injection into the GC–MS. Additionally, SEM imaging was used to observe the epicuticle surface of treated larvae under critical temperatures. The findings showed a direct relationship between increasing temperatures and the mortality rate of 3rd instar larvae, with complete mortality occurring in 20 min at 50 °C, in 15 min at 55 °C, and in just 10 min at 60 °C. Moreover, with an increase in temperature and exposure time, the weight of the larvae decreased significantly. GC–MS analysis unveiled that the waxy layer contained sixteen fatty acids within P. interpunctella cuticles; it was observed that as temperatures increased, there was a significant reduction in fatty acid levels. SEM imaging also revealed that rising temperatures led to a dramatic decrease in cohesion within the epicuticle layer; altering its physical and chemical structure caused dehydration, ultimately leading to death. These results suggest that utilizing critical temperatures for short durations can effectively control P. interpunctella populations.

Guided wave elastography of human skins with a layered model incorporating the effect of muscle state

In vivo mechanical characterization of skin finds broad applications in understanding skin aging, diagnosis of some skin diseases and assessing the effectiveness of diverse skin care strategies. Skin has a layered structure consisting of the epidermis, dermis and subcutaneous layers. Although much effort has been made towards mechanical characterization of skin, it remains a challenging issue to measure the mechanical properties of an individual layer in vivo. To address this issue, we here report a guided wave elastography method for layered human skin which incorporates the effect of muscle states. Both finite element simulations and phantom experiments have been performed to validate the method. For skin-mimicking phantoms with different fat layer thicknesses, the errors in the identified shear modulus of the skin layers are no more than 11 %. In vivo experiments have been carried out on 6 healthy subjects to demonstrate the potential use of the method in clinics. A statistical analysis indicates the muscle contraction contributes to the stiffening of the skin (p < 0.001). Finally, a phase diagram has been constructed to reveal the extent to which muscle sates (including both passive and active states) affect the measurement of elastic modulus of a skin layer, which may guide the application of the method in practice.

Secretory structures and histochemistry of roots, stem, and leaves of medicinal plant Fibraurea tinctoria Lour.

Fibraurea tinctoria Lour. (Menispermaceae) is a medicinal plant used by many local tribes in Indonesia and other countries. This species has pharmacological potential, such as antimalaria, antibacterial, antitumor, antioxidant, anticancer, antidiabetic, anti-inflammatory, and hepato-protector. However, the secretory structures and sites of secondary metabolite accumulation still need to be studied. This study aimed to explore the secretory structures and reveal the accumulation sites of the main classes of secondary metabolites in the root, stem, and leaves of F. tinctoria. Histochemical analysis using various specific reagents was performed on freehand sections of the fresh organs to detect alkaloids, phenolics, terpenoids, and lipophilic compounds. Observations of secretory structures were carried out using light microscopy. The result showed that idioblast was the predominant secretory structure in the plant organs and contained all the chemical groups investigated, while laticifer accumulated alkaloids were found only in the stem. Some secondary metabolites were localized in the xylem, intercellular space, and cuticle layer. Crystals were observed in the root, stem, and leaf of this species. These results might be helpful as guide information for extracting the particular plant parts to obtain the desired secondary metabolites. It suggested that leaves are a potential alternative source of medicinal raw material of this species, in addition to the stem. RESEARCH HIGHLIGHTS: The first study on secretory structures of Fibraurea tinctoria. Secondary metabolites in F. tinctoria organs accumulate in specialized and unspecialized structures. The idioblast is the primary secretory structure in the organs of F. tinctoria spreading over the root, stem, and leaves.

Plant natural product-based pesticides in crop protection: semi-synthesis, mono-crystal structures and agrochemical activities of osthole ester derivatives, and study of their toxicology against Tetranychus cinnabarinus (Boisduval).

Owing to large amounts of synthetic pesticides being extensively and unreasonably used for crop protection, currently, resistance and negative impacts on human health and environment safety have appeared. Therefore, development of potential pesticide candidates is highly urgent. Herein, a series of ester derivatives of osthole were designed and synthesized as pesticidal agents. Six spatial configurations of 4'-(p-toluenoyloxy)osthole (4b), 4'-(m-fluorobenzoyloxy)osthole (4f), 4'-(p-fluorophenylacetyloxy)osthole (4m), 4'-(3'',4''-methylenedioxybenzoyloxy)osthole (4q), 4'-formyloxyosthole (4u) and 4'-acetyloxyosthole (4v) were determined by X-ray mono-crystal diffraction. Compounds 4b, 4'-(p-chlorobenzoyloxy)osthole (4g), 4'-(m-chlorobenzoyloxy)osthole (4h), 4'-(p-bromobenzoyloxy)osthole (4i) and 4'-(2''-chloropyridin-3''-ylcarbonyloxy)osthole (4p) showed higher insecticidal activity than toosendanin against Mythimna separata Walker; notably, compound 4b displayed 1.8 times insecticidal activity of the precursor osthole. Against Tetranychus cinnabarinus Boisduval, compounds 4g and 4h showed 3.3 and 2.6 times acaricidal activity of osthole, and good control effects in the glasshouse. Scanning electron microscopy assay demonstrated that compound 4g can damage the cuticle layer of T. cinnabarinus resulting in death. Compounds 4g and 4h can be further studied as lead pesticidal agents for the management of M. separata and T. cinnabarinus. These results will pave the way for application of osthole derivatives as agrochemicals. © 2024 Society of Chemical Industry.

Impact of Skin Exposure to Benzo[a]pyrene in Rat Model: Insights into Epidermal Cell Function and Draining Lymph Node Cell Response.

The skin is a direct target of the air pollutant benzo[a]pyrene (BaP). While its carcinogenic qualities are well-studied, the immunotoxicity of BaP after dermal exposure is less understood. This study examines the immunomodulatory effects of a 10-day epicutaneous BaP application, in environmentally/occupationally relevant doses, by analyzing ex vivo skin immune response (skin explant, epidermal cells and draining lymph node/DLN cell activity), alongside the skin's reaction to sensitization with experimental hapten dinitrochlorobenzene (DNCB). The results show that BaP application disrupts the structure of the epidermal layer and promotes immune cell infiltration in the dermis. BaP exposure led to oxidative stress in epidermal cells, characterized by decreased reduced glutathione and increased AHR and Cyp1A1 expression. Production and gene expression of proinflammatory cytokines (TNF, IL-1β) by epidermal cells decreased, while IL-10 response increased. Decreased spontaneous production of IFN-γ and IL-17, along with unchanged IL-10, was observed in DLC cells, whereas ConA-stimulated production of these cytokines was elevated. Local immunosuppression caused by BaP application seems to reduce the skin's response to an additional stimulus, evidenced by decreased effector activity of DLN cells three days after sensitization with DNCB. These findings provide new insight into the immunomodulatory effects and health risks associated with skin exposure to BaP.

A Mouse Model for Conditional Expression of Activated β-Catenin in Epidermal Keratinocytes.

We report the generation and characterization of the K5: CAT bigenic mouse in which the constitutively activated form of β-catenin (ΔN89 β-catenin) is conditionally expressed in cytokeratin-5 (K5) positive epidermal keratinocytes. Following short-term doxycycline intake during the telogen resting phase, the adult K5: CAT bigenic develops enlarged pilosebaceous units that expand deep into the dermis, an expansion usually observed during the anagen growth phase. Prolonged doxycycline treatment results in significant thickening and folding of the K5: CAT epidermis. During this persistent induction period, there is clear evidence of increased keratinocyte proliferation, particularly in the epidermal basal cell layer and the outer root sheath of the hair follicle. This unscheduled increase in cellular proliferation likely explains the decrease in hair density observed in the K5: CAT mouse following persistent doxycycline intake. Numerous hyperplastic endometrioid cysts, which display cornification toward their lumens, are also observed during this treatment period. Remarkably, de-induction of ΔN89 β-catenin expression through doxycycline withdrawal results in a marked reversal of the skin phenotype, suggesting that these morphological changes are dependent on continued signaling by β-catenin and/or its downstream molecular mediators. Joining a small group of mouse models for conditional β-catenin signaling, our K5: CAT mouse model will be particularly useful in identifying those molecular mediators of β-catenin that are responsible for initiating and maintaining these phenotypic responses in the K5: CAT skin. Such studies are predicted to shed more light on β-catenin signaling in epidermal epithelial morphogenesis, hair follicle cycling, and hair growth pathologies.