Search

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Pododermatitis aseptica hemorrhagica circumscripta is associated with metalloproteinase 2 weakening of distal phalangeal suspensory structures and sinkage of the distal phalanx in the claw capsule. Pressure from the tuberculum flexorium on the sole epidermis and dermis produces hemorrhagic tissue injury and defective horn production appearing as yellow-red, softened claw horn in region 4 of the sole. A model of the MAPK/ERK signal cascade orchestrating epidermal-dermal homeostasis was employed to determine if sterile inflammatory responses are linked to disturbed signal transduction for epidermal homeostasis in sole epidermis and dermis. The objective was to assess shifts in target genes of inflammation, up- and downstream MAPK/ERK signal elements, and targeted genes supporting epidermal proliferation and differentiation. Sole epidermis and dermis were removed from lateral claws bearing lesions of PAHC, medial claws from the same limb and lateral claws from completely normal limbs of multiparous, lactating Holstein cows. The abundance levels of targeted transcripts were evaluated by real-time PCR. Lesion effects were assessed by ANOVA, and mean comparisons were performed with t -tests to assess variations between mean expression in ulcer-bearing or medial claw dermis and epidermis and completely normal lateral claw dermis and epidermis or between ulcer-bearing dermis and epidermis and medial claw dermis and epidermis. The lesions were sterile and showed losses across multiple growth factors, their receptors, several downstream AP1 transcription components, CMYC, multiple cell-cycle and terminal differentiation elements conducted by MAPK/ERK signals and β 4, α 6, and collagen 17A hemidesmosome components. These losses coincided with increased cytokeratin 6, β 1 integrin, proinflammatory metalloproteinases 2 and 9, IL1B and physiologic inhibitors of IL1B, the decoy receptor, and receptor antagonist. Medial claw epidermis and dermis from limbs with lateral claws bearing PAHC showed reductions in upstream MAPK/ERK signal elements and downstream targets that paralleled those in hemorrhagic lesions. Inhibitors of IL1B increased in the absence of real increases in inflammatory targets in the medial claw dermis and epidermis. Losses across multiple signal path elements and downstream targets were associated with negative effects on targeted transcripts supporting claw horn production and wound repair across lesion-bearing lateral claws and lesion-free medial claw dermis and epidermis. It was unclear if the sterile inflammation was causative or a consequence of these perturbations. [ABSTRACT FROM AUTHOR]

Local gene therapies, including in vivo genome editing, are highly anticipated for the treatment of genetic diseases in skin, especially the epidermis. While the adeno-associated virus (AAV) is a potent vector for in vivo gene delivery, the lack of efficient gene delivery methods has limited its clinical applications. To optimize the AAV gene delivery system with higher gene delivery efficiency and specificity for epidermis and keratinocytes (KCs), using AAV capsid and promoter engineering technologies. AAV variants with mutations in residues reported to be critical to determine the tropism of AAV2 for KCs were generated by site-directed mutagenesis of AAVDJ. The infection efficiency and specificity for KCs of these variants were compared with those of previously reported AAVs considered to be suitable for gene delivery to KCs in vitro and in vivo. Additionally, we generated an epidermis-specific promoter using the most recent short-core promoter and compared its specificity with existing promoters. A novel AAVDJ variant capsid termed AAVDJK2 was superior to the existing AAVs in terms of gene transduction efficiency and specificity for epidermis and KCs in vitro and in vivo. A novel tissue-specific promoter, termed the K14 SCP3 promoter, was superior to the existing promoters in terms of gene transduction efficiency and specificity for KCs. The combination of the AAVDJK2 capsid and K14 SCP3 promoter improves gene delivery to epidermis in vivo and KCs in vitro. The novel AAV system may benefit experimental research and development of new epidermis-targeted gene therapies. • A novel AAV capsid termed AAVDJK2 was developed and was superior to existing AAVs in terms of gene transduction efficiency and specificity for keratinocytes in vitro and in vivo. • A novel tissue-specific promotor termed K14 SCP3 promotor was developed and was superior to existing promoters in terms of gene transduction efficiency and specificity for keratinocytes in vitro and in vivo. • The novel AAV system benefits experimental research and development of new epidermis-targeted gene therapies. [ABSTRACT FROM AUTHOR]

• Upcycled canola meal extract (CME) showed anti-photoaging effects in hairless mice. • CME reduced the number, mean length, and mean depth of wrinkles. • CME inhibited the increase of epidermal thickness induced by UVB radiation. • CME increased catalase activity and hydroxyproline content in mouse skin. • CME inhibited the phosphorylation of MAPKs such as ERK, JNK, and p38. • CME reduced MMP-2, -9, and -13 production in mice in response to UVB radiation. Canola meal, a by-product of processing canola into oil, reportedly contains high amounts of phenolic compounds and proteins. However, as canola meal is primarily used as feed for livestock, advances in multiple research fields are required to broaden its potential applications. Photoaging is caused by continuous exposure to ultraviolet (UV) radiation from sunlight. UV radiation generates reactive oxygen species and destroys collagen in the skin, thickening the epidermis, reducing elasticity, and causing wrinkles. We hypothesized that canola meal extract (CME) can mitigate the damage to skin associated with wrinkles induced by exposure to UVB radiation. To evaluate the anti-wrinkle effect, we administered CME orally to 40 female Hos:HR-1 hairless mice divided into 5 groups: (1) control mice, (2) a UVB group, and (3−5) CME-treated groups (CME−250, 500, and 1000 mg/kg body weight/day, respectively). All groups except the controls were irradiated with UVB 3 times a week to create wrinkles due to photoaging. CME administration inhibited the increase of the number, mean length, and mean depth of wrinkles induced by UVB radiation as assessed using a skin replica. Histopathological image analysis revealed that CME administration resulted in a decrease in epidermal thickness and an increase in collagen content, while increasing catalase activity and hydroxyproline content in skin tissues. CME administration inhibited the phosphorylation of mitogen-activated protein kinase and decreased the production of collagenase and gelatinase. These results suggest that CME, an upcycled material, has the potential to develop into a healthful and functional food ingredient with anti-wrinkling effects. Administration of CME to hairless mouse decreased the number, length, and depth of wrinkles and epidermal thickness. CME administration also increased antioxidant enzyme activity and hydroxyproline content in skin tissue and inhibited phosphorylation of MAPKs, reducing the production of collagenase and gelatinase. These results suggest that CME mitigates skin wrinkles caused by UVB radiation. CME, canola meal extract; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; UVB, ultraviolet B. [Display omitted] [ABSTRACT FROM AUTHOR]

Skin denervation has been shown to cause remission of psoriatic lesions in patients, which can reappear if reinnervation occurs. This effect can be induced by the activation of dendritic cells through sensory innervation. However, a direct effect of nerves on the proliferation of keratinocytes involved in the formation of psoriatic plaques has not been investigated. We developed, by tissue engineering, a model of psoriatic skin made of patient skin cells that showed increased keratinocyte proliferation and epidermal thickness compared to healthy controls. When this model was treated with CGRP, a neuropeptide released by sensory neurons, an increased keratinocyte proliferation was observed in the psoriatic skin model, but not in the control. When a sensory nerve network was incorporated in the psoriatic model and treated with capsaicin to induce neuropeptide release, an increase of keratinocyte proliferation was confirmed, which was blocked by a CGRP antagonist while no difference was noticed in the innervated healthy control. We showed that sensory neurons can participate directly to keratinocyte hyperproliferation in the formation of psoriatic lesions through the release of CGRP, independently of the immune system. Our unique tissue-engineered innervated psoriatic skin model could be a valuable tool to better understand the mechanism by which nerves may modulate psoriatic lesion formation in humans. This study shows that keratinocytes extracted from patients' psoriatic skin retain, at least in part, the disease phenotype. Indeed, when combined in a 3D model of tissue-engineered psoriatic skin, keratinocytes exhibited a higher proliferation rate, and produced a thicker epidermis than a healthy skin control. In addition, their hyperproliferation was aggravated by a treatment with CGRP, a neuropeptide released by sensory nerves. In a innervated model of tissue-engineered psoriatic skin, an increase in keratinocyte hyperproliferation was also observed after inducing neurons to release neuropeptides. This effect was prevented by concomitant treatment with an antagonist to CGRP. Thus, this study shows that sensory nerves can directly participate to affect keratinocyte hyperproliferation in psoriasis through CGRP release. [Display omitted] [ABSTRACT FROM AUTHOR]

Although laurocapram (Azone) significantly enhances the skin permeation of drugs, its development was hindered by its skin irritation. We then developed an Azone-mimic ionic liquid (IL-Azone), composed of less irritating cationic ε -caprolactam and anionic myristic acid. IL-Azone dissociates to the original cation and anion in the presence of water in the formulation. We tried to select a formulation suitable for IL-Azone in the present study. Each formulation contained 5 % of either Azone or IL-Azone along with the model drug antipyrine, and skin permeation experiments of the drug were conducted. The results revealed that IL-Azone did not enhance skin permeation when combined with most formulations tested. However, a notable and rapid enhancement in skin permeation was observed when combined with white petrolatum. This effect could be attributed to the minimal water content in white petrolatum, which prevented IL-Azone degradation. Furthermore, its permeation-enhancing effects from IL-Azone in white petrolatum were more pronounced and rapid than Azone. The rapid onset observed with IL-Azone can be attributed to its degradation into its original components at the interface between the stratum corneum and the living epidermis, which results in a shorter lag time before achieving a steady-state concentration in the SC compared to Azone. [ABSTRACT FROM AUTHOR]

Microneedle drug delivery has recently emerged as a clinical method, and dissolving microneedles (DMNs) offer exclusive simplicity and efficiency, compared to the other kinds of microneedles. The tips of most currently available DMNs are cone/house-shaped to result in a lower penetration force. Penetration of the needle tips into the skin relies mainly on the back tape or external pressure, and their adhesion to the skin is relatively low. In addition, only the drug in the part of tips that are pierced into the dermis can be dissolved, resulting in drug waste. Inspired from the barbed structure of the honeybee stinger, we reported substrate-free DMNs with a barbed structure by a dual-molding process, which is suitable for mass production. Those DMNs showed 3-fold greater adhesion force between the needle tips and the skin, better dissolution and deeper penetration than house-shaped DMNs in vivo under the same conditions. For the in situ treatment of psoriasis in mice, the barbed DMNs required only the half dose of house-shaped DMNs to achieve similar efficacy. We reported substrate-free DMNs with barbed structure by dual-molding process, which showed 3-fold greater adhesion force between needle tips and skin, better dissolution and deeper penetration than house-shaped one. [Display omitted] [ABSTRACT FROM AUTHOR]

Tissue-engineered skin is ideal for clinical wound repair. Restoration of skin tissue defects using tissue-engineered skin remains a challenge owing to insufficient vascularisation. In our previous study, we developed a 3D bioprinted model with confined force loading and demonstrated that the confined force can affect vascular branching, which is regulated by the YAP signalling pathway. The mechanical properties of the model must be optimised to suture the wound edges. In this study, we explored the ability of a GelMA-HAMA-fibrin scaffold to support the confined forces created by 3D bioprinting and promote vascularisation and wound healing. The shape of the GelMA-HAMA-fibrin scaffold containing 3% GelMA was affected by the confined forces produced by the embedded cells. The GelMA-HAMA-fibrin scaffold was easy to print, had optimal mechanical properties, and was biocompatible. The constructs were successfully sutured together after 14 d of culture. Scaffolds seeded with cells were transplanted into skin tissue defects in nude mice, demonstrating that the cell-seeded GelMA-HAMA-fibrin scaffold, under confined force loading, promoted neovascularisation and wound restoration by enhancing blood vessel connections, creating a patterned surface, growth factors, and collagen deposition. These results provide further insights into the production of hydrogel composite materials as tissue-engineered scaffolds under an internal mechanical load that can enhance vascularisation and offer new treatment methods for wound healing. Tissue-engineered skin is ideal for use in clinical wound repair. However, treatment of tissue defects using synthetic scaffolds remains challenging, mainly due to slow and insufficient vascularization. Our previous study developed a 3D bioprinted model with confined force loading, and demonstrated that confined force can affect vascular branching regulated by the YAP signal pathway. The mechanical properties of the construct need to be optimized for suturing to the edges of wounds. Here, we investigated the ability of a GelMA-HAMA-fibrin scaffold to support the confined forces created by 3D bioprinting and promote vascularization in vitro and wound healing in vivo. Our findings provide new insight into the development of degradable macroporous composite materials with mechanical stimulation as tissue-engineered scaffolds with enhanced vascularization, and also provide new treatment options for wound healing. [Display omitted] [ABSTRACT FROM AUTHOR]

A complete in vitro skin model, containing resident cell types is needed to understand physiology and to consider the role of immune and endothelial cells in dermal drug testing. In this study, a cell extraction technique was developed to isolate resident skin cells from the same human donor while preserving the immune and endothelial cells. Then those cells were used to reconstruct an autologous, vascularized, and immunocompetent Tissue-Engineered Skin model, aviTES. Phenotypic characterization of the viable cells was performed on freshly isolated cells and after thawing through flow cytometry. Dermal cell extracts were characterized as fibroblasts, endothelial and immune cells, and the average amount of each cell type represents 4, 0.5, and 1 million viable cells per g of the dermis, respectively. The 3D models, TES and aviTES, were characterized by a fully differentiated epidermis that showed an increase in the presence of Ki67+ cells in the basolateral layer of the aviTES model. Capillary-like network formation, through the self-assembly of endothelial cells, and the presence of functional immune cells were identified through immunofluorescence staining in aviTES. In addition, the aviTES model was immunocompetent, as evidenced by its capacity to increase the production of pro-inflammatory cytokines TNF-α, MIP-1α, and GM-CSF following LPS stimulation. This study describes an autologous skin model containing a functional resident skin immune system and a capillary network. It provides a relevant tool to study the contribution of the immune system to skin diseases and inflammatory responses and to investigate resident skin cell interactions and drug development. There is an urgent need for a complete in vitro skin model containing the resident cell types to better understand the role of immune and endothelial cells in skin and to be able to use it for drug testing. Actual 3D models of human skin most often contain only fibroblasts and keratinocytes with a limited number of models containing endothelial cells or a limited variety of immune cells. This study describes an autologous skin model containing a functional resident skin immune system and a capillary network. It provides a relevant tool to study the contribution of the immune system to skin diseases and inflammatory responses and to investigate interactions between resident skin cell, improving our capacity to develop new drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

Papillary and reticular dermis show distinct extracellular matrix (ECM) and vascularization corresponding to their specific functions. These characteristics are associated with gene expression patterns of fibroblasts freshly isolated from their native microenvironment. In order to assess the relevance of these fibroblast subpopulations in a tissue engineering context, we investigated their contribution to matrix production and vascularization using cell sheet culture conditions. We first performed RNA-seq differential expression analysis to determine whether several rounds of cell amplification and high-density culture affected their gene expression profile. Bioinformatics analysis revealed that expression of angiogenesis-related and matrisome gene signatures were maintained, resulting in papillary and reticular ECMs that differ in composition and structure. The impact of secreted or ECM-associated factors was then assessed using two independent 3D angiogenesis assays: -1/ a fibrin hydrogel-based assay allowing investigation of diffusible secreted factors, -2/ a scaffold-free cell-sheet based assay for investigation of fibroblast-produced microenvironment. These analyses revealed that papillary fibroblasts secrete highly angiogenic factors and produce a microenvironment characterised by ECM remodelling capacity and dense and branched microvascular network, whereas reticular fibroblasts produced more structural core components of the ECM associated with less branched and larger vessels. These features mimick the characteristics of both the ECM and the vasculature of dermis subcompartments. In addition to showing that skin fibroblast populations differentially regulate angiogenesis via both secreted and ECM factors, our work emphasizes the importance of papillary and reticular fibroblasts for engineering and modelling dermis microenvironment and vascularization. Recent advances have brought to the forefront the central role of microenvironment and vascularization in tissue engineering for regenerative medicine and microtissue modelling. We have investigated the role of papillary and reticular fibroblast subpopulations using scaffold-free cell sheet culture. This approach provides differentiated cells conditions allowing the production of their own microenvironment. Analysis of gene expression profiles and characterisation of the matrix produced revealed strong and specific angiogenic properties that we functionally characterized using 3D angiogenesis models targeting the respective role of either secreted or matrix-bound factors. This study demonstrates the importance of cell-generated extracellular matrix and questions the importance of cell source and the relevance of hydrogels for developing physio-pathologically relevant tissue engineered substitutes. [Display omitted] [ABSTRACT FROM AUTHOR]

Eyelid defects can occur secondary to tumours, trauma, burns, and congenital factors. Among the most challenging aspects of eyelid reconstruction is the rebuilding of a tarsal substitute due to its delicate and multi-layered tissue composition. Attempts to use biomaterials for posterior lamellar reconstruction are intended to provide an alternative to traditional autograft reconstructions. In this review, we aimed to assess the types of biomaterials used for the reconstruction of the posterior lamella associated with eyelid defects and the associated clinical outcomes. A literature search was conducted on Pubmed, Prospero, Dynamed, DARE, EMBASE, and COCHRANE databases. A total of 15 articles fulfilled the inclusion criteria, and 129 patients with 142 eyelids reconstructed, using artificial grafts, were included in the review. Acellular dermis allograft (AlloDerm®, LifeCell) (n = 49) was the most common artificial graft used. A meta-analysis was performed, which demonstrated a pooled success rate of artificial grafts of 99% (95% CI 96–100, p = 0.05; I 2 = 40%, total complications seen 39% (95% CI 96–100, p = 0.05; I 2 = 40%) and re-operation rates of 5.6% (n = 8). The biomaterials used demonstrated an overall success rate of 99%, which is similar if not greater than that reported with the use of traditional autograft reconstruction techniques, with similar complications and fewer re-operations than autografts. This suggests that clinicians should consider the clinical use of artificial grafts for posterior lamellar reconstruction. [ABSTRACT FROM AUTHOR]

Acellular dermal matrix (ADM) is generally used on implant-based breast operations; However, it can increase surgical site infection. Many immersion solutions are applied to ADM, however, the most effective solution is unknown. The purpose of this study is to determine the effect of different solutions on the biofilm formation and mechanical properties of ADM. Aseptic porcine-derived ADMs were immersed in 5 different solutions for 30 min; sterile normal saline, 10% povidone-iodine, 0.5% chlorhexidine, antibiotics (cefazolin, gentamicin, and vancomycin), and taurolidine. They are transferred to 10 ml suspension of methicillin-sensitive/resistant Staphylococcus aureus (MSSA/MRSA) or Staphylococcus epidermidis and an overnight culture was performed. After rinsing and sonication to obtain the biofilm on ADM, colony forming unit (CFU) was measured. In addition, the maximum load before ADM deformation and the elongation length of ADM at the start of the maximum load was determined. Regardless of strains, povidone-iodine, chlorhexidine, and taurolidine group had lower CFUs than the saline group with statistical significance. Meanwhile, the antibiotics group did not show statistical difference from the saline group. Moreover, only taurolidine group showed higher tensile strength (MRSA, p = 0.0003; S. epidermidis , p = 0.0023) and elongation length (MSSA, p = 0.0015) than the saline group. The antibiotics and chlorhexidine group yielded lower tensile strength and elongation length than the povidone-iodine and taurolidine groups. It was suggested that the 10% povidone-iodine or taurolidine solution is effective. In contrast, the antibiotics solution could be considered as an effective intraoperative solution. [ABSTRACT FROM AUTHOR]

Background: Autologous cultured epidermis (CE) is successfully used in burn care, but it requires a manufacturing time of three weeks and is very expensive owing to its custom-made nature of treatment. To compensate this disadvantage, dried allogeneic CE promises a novel therapeutic approach; and previous reports have demonstrated its efficacy in promoting wound healing using a murine skin defect model. Herein, a prospective clinical study was conducted to confirm the safety and efficacy of dried allogeneic CE for wound treatment.Methods: Dried CE was manufactured using donor keratinocytes obtained from excess surgical skin and applied to skin defects that were at least 3 cm in length and less than 10 % of the body surface area of the patients. The patients were observed for 14 days after CE application. The primary endpoint was the incidence of adverse events and the secondary endpoint was the percentage of wound healed since baseline, on days 7 and 14. Furthermore, as a stratified analysis, the percentage of wound healed, specified as deep dermal burns, was calculated.Results: Six patients (five burns and one skin ulcer after necrotizing fasciitis) enrolled in the study. As a serious adverse event, a local infection was observed in one patient, which resolved by debridement and conventional skin grafting. Other adverse events that were potentially related to this treatment included two cases of skin erosion, and one case of systemic fever. No unresolved adverse events remained at the end of the study period. The percentage of wound healed was 73.4 ± 19.2 % on Day 7, and 92.2 ± 11.8 % on Day 14. When the targeted disease was restricted to deep dermal burns, the percentage of wound healed was 69.9 ± 28.9 % on Day 7 and 90.5 ± 13.2 % on Day 14.Conclusion: Treatment with dried CE was safely performed without any unresolved severe adverse effects. Dried CE is a new and promising modality for skin defect treatment, such as burns and ulcers, and is expected to compensate for the disadvantages of autologous CE. However, large-scale clinical trials are required to confirm their efficacy. [ABSTRACT FROM AUTHOR]

Pruritus (or itch) is an unpleasant sensation leading to a desire to scratch. In the epidermis, there are selective C or Aδ epidermal nerve endings that are pruriceptors. At their other ends, peripheral neurons form synapses with spinal neurons and interneurons. Many areas in the central nervous system are involved in itch processing. Although itch does not occur solely because of parasitic, allergic, or immunologic diseases, it is usually the consequence of neuroimmune interactions. Histamine is involved in a minority of itchy conditions, and many other mediators play a role: cytokines (eg, IL-4, IL-13, IL-31, IL-33, and thymic stromal lymphopoietin), neurotransmitters (eg, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, neuropeptide Y, NBNP, endothelin 1, and gastrin-releasing peptide), and neurotrophins (eg, nerve growth factor and brain-derived neurotrophic factor). Moreover, ion channels such as voltage-gated sodium channels, transient receptor potential vanilloid 1, transient receptor ankyrin, and transient receptor potential cation channel subfamily M (melastatin) member 8 play a crucial role. The main markers of nonhistaminergic pruriceptors are PAR-2 and MrgprX2. A notable phenomenon is the sensitization to pruritus, in which regardless of the initial cause of pruritus, there is an increased responsiveness of peripheral and central pruriceptive neurons to their normal or subthreshold afferent input in the context of chronic itch. [ABSTRACT FROM AUTHOR]

This is the first study describing the ultrastructure of the digestive system of a member of the marine teleost-infecting aporocotylid lineage, Aporocotyle simplex (Odhner, 1900), a blood parasite of the long rough dab Hippoglossoides platessoides (Fabricus, 1780) from the Norwegian Sea, Norway. The presence of particular morphological characters of the extensive A. simplex foregut and the four caecal ramifications are described. These show a syncytiality of the digestive epithelial lining with sunken perikarya in the foregut region and intraepithelial nuclei in the caecal region. Based on characteristic features of the pharyngeal muscle patterns in the Digenea, our results support the occurrence of a rudimentary pharynx in A. simplex. The short anterior esophageal portion retains tegumental cytoplasmic inclusions, but the middle-posterior esophageal portion shows considerable morphological modifications of the esophageal cytoplasm and sunken bodies modified into well-developed esophageal glands. These consist of undifferentiated cells, cells in different stages of differentiation and disintegrated cells, showing their renovation and apoptosis, controlled by the nervous system. Our data provide morphological evidence on the digestion of host erythrocytes within the lumen of the middle-posterior esophageal region. Morphological data indicated also the existence of the gastrodermal pathway, completing the digestive process. The revealed differences in the pharyngeal foregut region and in the caecal cytomorphology in marine A. simplex and the previously studied freshwater Sanguinicola inermis may support molecular data on the existence of divergent evolutionary lineages of marine and freshwater teleost-infecting species, or new data assigning Sanguinicola and Aporocotyle as separate families. [ABSTRACT FROM AUTHOR]

A key requirement in forming the water permeability barrier in the mammalian epidermis is the oxidation of linoleate esterified in a skin-specific acylceramide by the sequential actions of 12R-lipoxygenase, epidermal lipoxygenase-3, and the epoxyalcohol dehydrogenase SDR9C7 (short-chain dehydrogenase-reductase family 7 member 9). By mechanisms that remain unclear, this oxidation pathway promotes the covalent binding of ceramides to protein, forming a critical structure of the epidermal barrier, the corneocyte lipid envelope. Here, we detected, in porcine, mouse, and human epidermis, two novel fatty acid derivatives formed by KOH treatment from precursors covalently bound to protein: a "polar" lipid chromatographing on normal-phase HPLC just before omega-hydroxy ceramide and a "less polar" lipid nearer the solvent front. Approximately 100 µg of the novel lipids were isolated from porcine epidermis, and the structures were established by UV-spectroscopy, LC-MS, GC-MS, and NMR. Each is a C18 fatty acid and hydroxy-cyclohexenone with the ring on carbons C9-C14 in the polar lipid and C8-C13 in the less polar lipid. Overnight culture of [14C]linoleic acid with whole mouse skin ex vivo led to recovery of the 14C-labeled hydroxy-cyclohexenones. We deduce they are formed from covalently bound precursors during the KOH treatment used to release esterified lipids. KOH-induced intramolecular aldol reactions from a common precursor can account for their formation. Discovery of these hydroxy-cyclohexenones presents an opportunity for a reverse pathway analysis, namely to work back from these structures to identify their covalently bound precursors and relationship to the linoleate oxidation pathway. [ABSTRACT FROM AUTHOR]

Although many superior capsule reconstruction (SCR) techniques are currently practiced in clinical settings, guidelines for choosing the appropriate graft material are lacking. Therefore, at most times, the surgeon's personal preference becomes the deciding factor. This study compared 2 fairly recent SCR techniques—SCR with biceps tendon (BT) autograft and SCR with human dermis (HD) allograft—by evaluating clinical and radiologic outcomes to aid the surgeon's decision in choosing the appropriate graft. Thirty-one patients underwent SCR using BT autograft (SCR BT), and 22 underwent SCR using HD allograft (SCR HD). SCR BT was selected for patients with a partial BT tear <20%, no severe inflammation signs, and favorable anchor conditions. SCR HD was performed in patients with a BT tear >20%, a superior labrum anterior-posterior (SLAP) lesion, severe inflammation, or subluxation. Range of motion (ROM), strength and shoulder function scoring, plain radiography, and magnetic resonance imaging were evaluated before and after surgery at regular intervals. In the SCR BT group, forward flexion ROM increased from 122° ± 43° to 149° ± 18° at 2 years postoperatively, whereas in the SCR HD group, forward flexion ROM improved from 129° ± 28° to 149° ± 18°. In the SCR BT group, internal rotation (IR) ROM increased from 5 ± 3 to 6 ± 2 at 2 years postoperatively, whereas in the SCR HD group, IR ROM improved from 5 ± 3 to 6 ± 1. Although ROM, strength, visual analog scale score, American Shoulder and Elbow Surgeons score, and Constant score all improved 2 years after surgery, no statistically significant differences were found. Six months after surgery, graft thickness was 3.58 ± 0.384 mm in the SCR BT group and 2.49 ± 0.326 mm in the SCR HD group (P <.001). At 2 years postoperatively, graft thickness was 3.54 ± 0.399 mm in the SCR BT group and 2.49 ± 0.306 mm in the SCR HD group (P <.001). The SCR HD group showed a negative correlation of −0.475 between graft thickness and IR ROM (P =.026). In the SCR BT group, a negative correlation of −0.466 was found between graft thickness and IR ROM (P =.008). A positive correlation of 0.363 was found between IR ROM and the acromiohumeral distance when the results were compared before and 2 years after surgery (P =.045). Both SCR using BT autograft and SCR using HD allograft tissue showed favorable results, and no significant difference was noted between the 2 techniques. Given that the 2 techniques show equally favorable results, the surgeon's personal preference in choosing the SCR technique appears to be acceptable. Understanding the costs and patient's characteristics may aid the surgeon in deciding on the graft material. [ABSTRACT FROM AUTHOR]

The mainstay of non-invasive scar management, consists of pressure therapy with customized pressure garments often combined with inlays, hydration by means of silicones and/or moisturizers as well as UV protection. It is generally accepted that scar dehydration resulting from impaired barrier function of the stratum corneum and expressed by raised trans epidermal water loss (TEWL) values, can lead to increased fibroblast activity and thereby hypertrophic scar formation. However, we have reached no consensus on exactly what optimal scar hydration is nor on barrier function repair: by means of silicone sheets, liquid silicone gels or moisturizers. Occlusive silicone sheets almost completely prevent TEWL and have been shown to be effective. Nevertheless, many important disadvantages due to excessive occlusion such as difficulties in applying the sheets exceeding 10–12 h, pruritus, irritation, and maceration of the skin are limiting factors for its use. To avoid these complications and to facilitate the application, liquid silicone gels were developed. Despite a reduced occlusion, various studies have shown that the effects are comparable to these of the silicone sheets. However, major limiting factors for general use are the long drying time, the shiny aspect after application, and the high cost especially when used for larger scars. Based on excellent clinical results after using three specific moisturizers for scar treatment in our patients, we wanted to investigate whether these moisturizers induce comparable occlusion and hydration compared to both each other and the widely recognized liquid silicone gels. We wanted to provide a more scientific basis for the kind of moisturizers that can be used as a full-fledged and cost-effective alternative to silicone gel. A total of 36 healthy volunteers participated in this study. Increased TEWL was created by inducing superficial abrasions by rigorous (20x) skin stripping with Corneofix® adhesive tape in squares of 4 cm². Three moisturizers and a fluid silicone gel were tested: DermaCress, Alhydran, Lipikar and BAP Scar Care silicone gel respectively. TEWL reducing capacities and both absolute (AAH) and cumulative (CAAH) absolute added hydration were assessed using a Tewameter® TM300 and a Corneometer® CM825 at different time points for up to 4 h after application. We found an immediate TEWL increase in all the zones that underwent superficial abrasions by stripping. Controls remained stable over time, relative to the ambient condition. The mean percentage reduction (MPR) in TEWL kept increasing over time with Alhydran and DermaCress, reaching a maximum effect 4 h after application. Silicone gel reached maximal MPR almost immediately after application and only declined thereafter. The silicone gel never reached the minimal MPR of Alhydran or DermaCress. Hydration capacity assessed through CAAH as measured by the Corneometer was significantly less with silicone gel compared to the moisturizers. Compared to silicone gel Lipikar provided similar occlusion and the improvement in hydration was highly significant 4 h after application. Based on the results of both our previous research and this study it is clearly demonstrated that the occlusive and hydrative effect of fluid silicone gel is inferior to the moisturizers used in our center. Lipikar hydrates well but is less suitable for scar treatment due to the lack of occlusion. A well-balanced occlusion and hydration, in this study only provided by Alhydran and DermaCress, suggests that moisturizers can be used as a scar hydration therapy that replaces silicone products, is more cost-effective and has a more patient-friendly application. • Unbalanced moisturizers provide hydration without adequate occlusion and can paradoxically lead to skin dehydration. • Well-balanced moisturizers provide strong occlusion and hydration of the stratum corneum with high longevity. • Well-balanced moisturizers are an alternative to silicone products in scar prevention and management. • DermaCress and Alhydran are examples of well-balanced moisturizers, making them ideal for scar hydration. • The occlusive properties of fluid silicone gels might be overrated and they do not provide true skin barrier restoration. [ABSTRACT FROM AUTHOR]

Core catchers are being installed in advanced light water reactors after TMI and Fukushima. The core catchers are designed to stabilise and cool molten corium within the reactor containment for a long time, reducing the risk of core meltdown. Some core catchers use sacrificial material to lower the specific volumetric heat release of the molten corium. The low density oxidic component of molten pool migrate to the top layer of the core catcher after melt-sacrificial material interaction. The high density metallic component migrate to the bottom layer. In the event that the core catcher is top flooded, this prevents metallic components from reacting with water and generate hydrogen. Post experimental analysis of the cooled stratified melt pool was performed. The experimental scaled down core catcher used reactor the prototypic sacrificial material while maintaining the actual reactor flooding conditions. About 550 kg of simulant corium was melted at about 2500 °C using heat of thermite reaction. The core catcher vessel was partially filled with sacrificial bricks. After the test, solidified debris samples from different locations of the core catcher model were analysed for density and SEM-EDS for quantitative and qualitative characterisation. Post-test analysis showed the melt inversion characteristics. [ABSTRACT FROM AUTHOR]

We describe the histological tissue damage and compare the healing process in 16 dairy calves disbudded at a mean age of 6 days by cauterization or alkaline caustic paste application. Biopsies were taken 2 days (T2) and 2 weeks (T14) after disbudding from sedated calves treated with local anaesthetic and non-steroidal anti-inflammatory drugs. At T2, the cauterized horn buds generally had eosinophilic coagulative necrosis of the epidermis and superficial dermis, bordered basally by a neutrophilic demarcation zone. Lateral to the direct heat contact area, dermal blood vessels were thrombosed, with wall damage and perivascular neutrophils. In the caustic paste-treated horn buds, the epidermis and dermis had diffuse full-thickness liquefactive necrosis directly under the paste contact area. The necrosis spread laterally in the dermis beyond the area of paste contact and was bordered by a neutrophilic infiltrate. At T14, the cauterized horn buds had epidermal to superficial dermal ulceration and crusting, dermal neutrophilic infiltration and granulation tissue formation. In contrast, most of the caustic paste-treated horn buds consisted of a superficial dermal crust or predominantly necrotic tissue fragments. The remaining viable areas had histiocytic inflammation with peripheral neutrophils and early granulation tissue formation. Caustic paste disbudding caused poorly demarcated lesions that were more severe and extensive and took longer to heal than those due to cautery. Cauterization induced a more intense acute reaction adjacent to the primary lesion compared with caustic paste. [ABSTRACT FROM AUTHOR]

Les conditions locales peuvent mettre en péril la réalisation de greffes cutanées en couverture de pertes de substance. Nous proposons ici une note technique, sur la réalisation de greffes cutanées autologues à greffons enfouis, dans des cas d'échec patent ou prévisible de greffes cutanées traditionnelles. Le protocole opératoire comprend la découpe de greffons dermoépidermiques de peau mince, en greffons carrés de quelques millimètres de largeur, pouvant être obtenus par système HUMECA. Ces greffons sont ensuite enfouis directement en profondeur du bourgeon de la perte de substance. On obtient alors des îlots épidermiques de cicatrisation éparses, puis une cicatrisation de la plaie par confluence de ceux-ci. Local conditions can lead to a failure of traditional skin grafts. We propose here our technique about the realization of autologous skin graft using it buried chipped grafts, for wounds in failure of treatments or at risk of failure. The protocol includes cutting the skin graft within little squared pieces of a few millimeters of length, that are then buried directly deep into the wound. We can then obtain little islands of epidermisation on the random places of the wound that will heal by confluence of those epidermal islands. [ABSTRACT FROM AUTHOR]

The cosmetics market has recently undergone changes as consumers increasingly seek sustainable products. In this context, agro-derived lignins have the potential for cosmetics applications. Thus, this study investigated the photoprotective activity and skin irritation potential (OECD TG 439 with SkinVitro-RHE, an in-house reconstructed human epidermis (RHE) model) of a kraft lignin (LE) and two LE-derived lignins modified by enzymatic reactions to achieve higher molecular weight (Mw) (R1: intermediate Mw and E60: highest Mw). Results showed that LE and R1 lignins present adequate photoprotective activity with averages Sun Protection Factor (SPF) of 33.8 ± 0.02 and 22.7 ± 0.04, respectively. The E60 also present adequate SPF (22.4 ± 0.2); however, due to its poor solubility, this lignin has potential application as a physical filter. In terms of safety, these lignins did not cause skin irritation or cellular and structural damage to the epidermis. Additionally, using an analysis based on the autofluorescence feature of lignin, no sign of the tested lignins was found in exposed RHE models, indicating that these three lignins did not penetrate the skin. Altogether, the results indicate a promising application of kraft lignins for sunscreen products regarding safer alternatives and product sustainability. Also, the SkinVitro-RHE showed to be a good model for evaluating the skin irritation potential of substances, including natural cosmetic ingredients. • Kraft lignins presented photoprotective activity with SPF similar to UV filters used in cosmetics. • Enzymatic reactions increase Mw of lignins, and depending on the Mw they can be used as organic or physical UV filters. • Kraft lignins do not cause skin irritation and morphological damage to the human epidermis. • SkinVitro-RHE is a good open-access RHE model to evaluate the skin irritation potential of substances. • Kraft lignins can contribute to products' sustainability as natural UV filters. [ABSTRACT FROM AUTHOR]

[Display omitted] • Amphiphilic polyoxazolines interact with membrane models, from simple lipid bilayer until their in vivo skin penetration. • Saturated lipid polyoxazolines insert immediately in simple phospholipid lipid bilayer and plasma membranes contrary to unsaturated ones. • Saturated and unsaturated amphiphilic polyoxazoline cross the stratum corneum and penetrate the upper epidermis of mice ear. • Amphiphilic polyoxazolines lipid nanocapsules penetrate the mice ear upper epidermis and successfully deliver the encapsulated quercetin. In this study, we evaluated the potential of amphiphilic polyoxazolines (POx) to interact with biological membranes thanks to models of increasing complexity, from a simple lipid bilayer using giant unilamellar vesicles (GUV), to plasma membranes of three different cell types, fibroblasts, keratinocytes and melanocytes, which are found in human skin. Upon assessing an excellent penetration into GUV membranes and cultured cells, we addressed POx's potential to penetrate the murine skin within an in vivo model. Exposure studies were made with native POx and with POx encapsulated within lipid nanocapsules (LNC). Our findings indicate that POx's interactions with membranes tightly depend on the nature of the alkyl chain constituting the POx. Saturated C 16 POx insert rapidly and efficiently into GUV and plasma membranes, while unsaturated C 18:2 POx insert to a smaller extent. The high amount of membrane-inserted saturated C 16 POx impacts cell viability to a greater extent than the unsaturated C 18:2 POx. The in vivo study, performed on mice, showed an efficient accumulation of both POx types in the stratum corneum barrier, reaching the upper epidermis, independently of POx's degree of saturation. Furthermore, the formulation of POx into lipid nanocapsules allowed delivering an encapsulated molecule, the quercetin, in the upper epidermis layers of murine skin, proving POx's efficacy for topical delivery of active molecules. Overall, POx proved to be an excellent choice for topical delivery, which might in turn offer new possibilities for skin treatments in diseases such as psoriasis or melanomas. [ABSTRACT FROM AUTHOR]

The human amniotic membrane contains the cellular parts obligatory for cell integration and tissue remodeling and has high tensile strength and persistence. We theorized that such material could function as a scaffold to improve the survival of ischemic tissue in random skin flaps. Male Albino Wistar rats (n = 30) were randomly assigned to three groups, each receiving a different model of AM on dorsal paravertebral areas: saline, amniotic membrane sheet, and micronized amniotic membrane. Digital photographs were taken, and the survival area was examined after one week. Histological analysis of skin flap tissue was performed, and the expression rate of vascular endothelial growth factor and apoptotic protein was examined. The survival percentage increased over time in all groups; however, one week after the implanted AM was increased survival in both experimental groups, with significantly greater than in the group control. In the experimental groups, there was a more regular arrangement of collagen and improved epithelialization in the flap tissue, also an increased number of inflammatory cells was observed in the control group. Additionally, VEGF and apoptotic protein expression, respectively, were significantly lower and greater in the control group than in the experimental groups. These results show that micronized membrane is an excellent scaffold for promoting flap survival. [ABSTRACT FROM AUTHOR]

Si Jun Zi Tang (SJZT) is a famous traditional Chinese medicine formula composing of 4 herbal medicines (Ginseng Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Poria, and Glycyrrhizae Radix et Rhizoma) with tonifying spleen and anti-aging effects. It is also known that SJZT can be used to tone, nourish the skin and accelerate wound healing. However, due to the complexity of the formulation, the anti-aging especially anti-skin aging mechanisms as well as the key components of SJZT have not been fully investigated. Therefore, further in vitro and in vivo experimental studies are particularly needed to investigate the anti-skin ageing efficacy of SJZT. The purpose of this article was to explore the therapeutic effect and possible pharmacological mechanism of SJZT in the treatment of skin aging by topical application using network pharmacology and to validate the findings using in vitro and in vivo tests. Network pharmacology method was applied to predict the underlying biological function and mechanism involved in the anti-skin aging effect of SJZT. Molecular docking was used to preliminarily predict the active components of SJZT-Skin Aging. UPLC QTOF MS/MS was carried out to analyze the chemical compounds. Finally, to confirm the anti-skin aging effort of SJZT, a mouse skin-aging model and UVB-induced EpiSCs (epidermal stem cells) senescence model were established. PPI network analysis and KEGG studies indicated that TP53, CDKN2A, TNF, IL6, and IL1B might be parts of the core targets associated with EpiSCs senescence. Furthermore, molecular docking suggested the top active components, glycyrrhizin, ginsenoside Rg5, ginsenoside Rh2, liquiritin, polyporenic acid C and atractylenolide II showed strong affinity to the key proteins involved in cellular senescence signaling. UPLC QTOF MS/MS analysis of SJZT confirmed the presence of these key components. In-vivo experiments revealed that SJZT could improve UVB-induced skin thickening, increase the number of collagen fibers, strengthen the structure of elastin fibers, and decrease the expression of MDA, as well as increase the expression of CAT and T-SOD in the skin tissue of mouse. And, in-vitro experiments indicated that SJZT could reduce ROS generation and oxidative stress, increase mitochondrial membrane potential, and upregulate the expression of stem cell markers. Moreover, SJZT could suppress the expression of p53, p-p53 and p21, downregulated p38 phosphorylation. Furthermore, the anti-cellular senescence effect of SJZT on EpiSCs disappeared after treatment with the p38 inhibitor adesmapimod. Taken all together, the regulation of senescence signaling in EpiSCs is an important mechanism of SJZT in combating skin aging. The research results indicate that SJZT has anti-skin aging effects on UVB-induced skin-aging model, possibly by mediating p38/p53 signaling pathway. These findings strongly demonstrate the great potential of SJZT as an active composite for anti-skin aging and cosmeceutical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Skin, as the outermost protective barrier of the body, becomes damaged with age and exposure to external stimuli. Dermal fibroblasts age and undergo apoptosis, which decreases collagen, collagen fibers, elastic fibers, hyaluronic acid, etc., leading skin to loss of elasticity and appearance of wrinkles. Skin aging is complex, involving several biological reactions，and various treatment methods are used to treat it. This review focuses on the importance of autophagy and cell proliferation in skin anti-aging, summarizes research progress on skin anti-aging by regulating autophagy and promoting the proliferation of dermal fibroblasts, and discusses future directions on skin anti-aging research. • Both promoting and inhibiting autophagy can prevent skin aging. • Promoting fibroblast proliferation is a good way to treat skin aging. • The combined use of different traditional anti-aging drugs can enhance the anti-aging effect of the skin. [ABSTRACT FROM AUTHOR]

Pulsed chirped beams propagating in human upper dermis tissue present intriguing characteristics and applications in medical imaging and diagnosis. This study delves into the analytical formulation of their propagation, specifically focusing on a pulsed chirped Laguerre higher-order cosh-Gaussian beam (LhchGB). Through the integration of power spectrum refractive index, extended Huygens-Fresnel integral, and Fourier Transform methods, we derive comprehensive analytical expressions for beam propagation. We numerically simulate the corresponding beam under different parameters and study the influence of each beam parameter on the spectral modifier during beam propagation. Additionally, we evaluate how the pulse duration and chirp parameter impact the spectral intensity at various observation positions. The results also indicate that as the pulsed chirped LhchGB traverses a considerable distance through this medium, it undergoes changes in its shape. The findings reveal that as the pulsed chirped LhchGB traverses through the dermis tissue, it undergoes significant changes in shape, underscoring its potential significance in medical applications. [ABSTRACT FROM AUTHOR]

San-Bai Decoction (SBD) is a classic whitening prescription originally recorded in the 'Introduction to Medicine' of the Ming Dynasty. SBD has been known for invigorating Qi and blood, promoting spleen and stomach, whitening skin, and fading melasma. However, its pharmacodynamic material basis and specific mechanism remain unclear. The aim of this study is to clarify the pharmacodynamic material basis of SBD and its mechanism of removing melasma. The positive and negative ion mass spectrum data of SBD extract were collected by UHPLC-Q-Exactive Orbitrap MS/MS, imported into Compound Discoverer (CD) 3.1 software, matched through the online database, and manually checked. Finally, the in vitro chemical components of SBD were classified. Similarly, the mass spectrum data of SBD in the serum of normal rats and melasma model rats were also analyzed by CD 3.1 software. The in vitro identified Compound file of SBD was imported into the Expected Compounds and the Generate Expected Compounds project was selected. The SBD compounds were then chosen under the Compound Section. All phase I and II reaction types related to SBD components were selected, and the metabolic platform of CD 3.1 software was utilized to process the results and obtain possible metabolites. The metabolites were scored and products with high scores were subsequently screened. According to literature comparison, the final metabolites of SBD in both normal rats and melasma model rats were determined and comprehensively analyzed. The Melasma model rats were constructed through intramuscular injection of progesterone and ultraviolet radiation B (UVB) irradiation. The preventing and treating effect of SBD on melasma were evaluated by regulating inflammation, epidermal collagen content, and oxidative stress. Additionally, the effect of SBD on the Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt)/Glycogen synthase kinase 3β (GSK3β) pathway was investigated through Western blot (WB) to explore its underlying mechanism on whitening and removing melasma efficacy. Ultimately, 94 components were identified in SBD, including 41 flavonoids, 27 organic acids, and 9 glycosides, 3 terpenoids, 2 amides, 2 aldehydes, 1 phenylpropanoid and 9 other compounds. In the blood of normal rat group, a total of 24 prototype components and 61 metabolites were identified. Similarly, there were19 prototype components and 44 metabolites identified from the blood of melasma model rats. Pharmacodynamic experiment results indicated that SBD effectively reduced the incidence of melasma, prevent the loss of epidermal collagen, and elevate the activity of superoxide dismutase and decrease the malondialdehyde content in both liver and skin. Interestingly, the WB results demonstrated that SBD effectively activated PI3K/Akt/GSK3β pathway, and down-regulated the expression of melanin-related proteins. For the first time, the components of SBD extracts, and its prototype components and metabolites in the blood of normal rats and melasma model rats were successfully identified by high-resolution liquid chromatography-mass spectrometry with CD software. Additionally, the differences of in vivo components of SBD between normal rats and melasma model rats were analyzed. The preventive and therapeutic effect of SBD on melasma was verified in the melasma model rats induced by progesterone and UVB irradiation, and its mechanism was related to activating PI3K/Akt/GSK3β pathway and downregulating the expression of melanin-related proteins. These results provide an experimental foundation for further research on the pharmacodynamic substance basis and pharmacodynamic mechanism of SBD, as well as developing new anti-melasma formula with SBD. [Display omitted] • UHPLC-Q-Exactive Orbitrap mass spectrometry was employed to analyze the constituents of San-Bai Decoction (SBD) extract and its prototype components and metabolites in the blood of normal rats and melasma model rats. • The preventive and therapeutic effect of SBD on melasma was verified in the melasma model rats. • The mechanism of SBD on melasma was related to activating PI3K/Akt/GSK3β pathway. [ABSTRACT FROM AUTHOR]

Picrasma quassioides (D. Don) Benn is a vascular plant belonging to the genus Picrasma of Simaroubaceae family and grows in Korea, China, India, Taiwan, and Japan. Picrasma quassioides extract has been reported to have anti-inflammatory, anti-bacterial, and anti-cancer properties. Moreover, this plant has been also traditionally used to alleviate symptoms of eczema, atopic dermatitis, psoriasis, scabies, and boils in skin. The Pq-EE has been reported in Chinese pharmacopoeia for its pharmacological effects on skin. However, the detailed mechanism on alleviating skin conditions is not understood. Hence, we investigated the skin improvement potential of Pq-EE against skin damage. We used the human keratinocyte cell line (HaCaT) and mouse melanoma cell line (B16F10) to study the effects of Pq-EE on the epidermis. Additionally, in vitro antioxidant assays were performed using a solution that included either metal ions or free radicals. In colorimetric antioxidant assays, Pq-EE inhibited free radicals in a dose-dependent manner. The Pq-EE did not affect cell viability and promoted cell survival under UVB exposure conditions in the MTT assay. The Pq-EE downregulated the mRNA levels of apoptotic factors. Moreover, MMP1 and inflammatory cytokine iNOS mRNA levels decreased with Pq-EE treatment. With regard to protein levels, caspases and cleaved caspases were more powerfully inhibited by Pq-EE than UVB-irritated conditions. p53 and Bax also decreased with Pq-EE treatment. The melanin contents and secretion were decreased at nontoxic concentrations of Pq-EE. The pigmentation pathway genes also were inhibited by treatment with Pq-EE. In summary, we suggest the cell protective potential of Pq-EE against UVB and ROS, indicating its use in UV-protective cosmeceutical materials. [Display omitted] • Pq-EE inhibits free radicals in a dose-dependent manner. • Pq-EE promotes cell survival under UVB exposure conditions. • Pq-EE suppresses UVB-induced apoptotic response. • Pq-EE downregulates MMP1 and iNOS mRNA levels. • Pq-EE decreases the melanin contents and secretion. [ABSTRACT FROM AUTHOR]

• Patients with exposed bones or tendons present significant clinical challenges. • Autologous flap transplantation leads to graft failure and tendon adhesion. • Artificial dermis reduces surgical risk and invasiveness. • Emphasis on exploring the potential benefits of artificial dermis. The clinical effects of artificial dermis in treating skin and soft tissue defects accompanied by bone or tendon exposure were assessed. A retrospective analysis was conducted on the clinical data of 45 cases of skin and soft tissue defects accompanied by bone or tendon exposure admitted to the trauma surgery department of Fujian Provincial Hospital between February 2018 and August 2020. They were divided into the artificial dermis and control groups. The wound was assessed using the Vancouver Scar Scale (mVSS), and the postoperative visual analogue scale (VAS) scores were recorded at 3, 6, 9, and 12 months after surgery. At the 12-month after surgery, skin sensation recovery was evaluated using the criteria of the British Medical Research Council (BMRC). The cases included 26 males and 19 females, aged 50 to 85 years. All patients were followed up for an average of 13.8 months (range: 12–18 months). Compared with controls, the wound healing time of the observation group was longer (35.8 ± 10.6 vs. 28.5 ± 4.8, P = 0.007), without significant differences for the number of operations and length of hospitalization. The mVSS scores were not different between groups (P group = 0.294), but the scores decreased with time (P time < 0.001), and the group×time interaction was significant (P interaction < 0.001). Similarly, the VAS scores were not different between groups (P group = 0.667), but the scores decreased with time (P time < 0.001); the group×time interaction was not significant (P interaction = 0.274). At the 12-month mark following the operation, in the artificial dermis group, the MCRR score was S3+ in 23 patients, while it ranged from S0 to S3 in two patients; in the control group, S3+ was observed in 17 patients, and S0-S3 in three (P = 0.815). Artificial dermis treatment is considered a safe and effective alternative therapy for patients with skin and soft tissue defects accompanied by bone or tendon exposure who cannot tolerate or are unwilling to undergo autologous skin flap transplantation. It offers the advantages of minimal donor site trauma, simplicity in operation, and favorable postoperative functional recovery. [ABSTRACT FROM AUTHOR]

• The leaf ontogenesis of Myrtoideae species revealed that the subepidermal layer is a hypodermis that originates from periclinal divisions of the ground meristem. • The occurrence of a hypodermis in representatives of Myrtaceae needs to be better studied and discussed in relation to the phylogeny of the family. • This study demonstrates the importance of ontogeny to understand plant structures so they can be properly used in taxonomic and phylogenetic interpretations. The ninth largest family of angiosperms is Myrtaceae, which comprises 127 genera and over 6000 species. The leaf anatomy of Myrtaceae has been widely studied and can be used in phylogenetic analyses and species delimitations in complexes within the family. A multiple epidermis and hypodermis have been described for the leaves of representatives of the family but have not been confirmed using ontogenetic studies, which could lead to incorrect interpretations about these tissues. Thus, we studied the leaf ontogenesis of the following 9 species in subfamily Myrtoideae: tribe Syzigieae - Syzigium cumini ; tribe Myrteae - Myrceugenia alpigena and M. euosma (subtribe Luminae), Psidium sartorianum, P. guajava, Campomanesia adamantium and Pimenta pseudocaryophyllus (subtribe Pimentinae), Myrcianthes pungens and M. gigantea (subtribe Eugeniinae). Shoot apices and leaves up to the fourth node were transversally and longitudinally sectioned following techniques used for plant anatomy. Leaf development in all species is from apical, intercalary, dorsal, marginal and plate meristematic activity. Protodermal periclinal divisions only occur to give rise to secretory cavities. The results show that in all the species the subepidermal layer is a hypodermis, which originates from periclinal divisions of the ground meristem. The occurrence of this layer could have phylogenetic implications according to reports in the literature, reinforcing the relationships among the subtribes in current topologies of Myrteae. However, the occurrence of a hypodermis in representatives of other subtribes of Myrteae and Syzigieae need to be better studied and discussed in relation to the phylogeny of Myrtaceae. [ABSTRACT FROM AUTHOR]

With the growing importance of alternative test methods that implement the 3Rs principles (Reduction, Refinement and Replacement) and the global importance of biological safety assessment data for medical devices is increasing. We have developed and optimized the 'KeraSkin™ Skin Irritation Test (KeraSkin™ SIT) for medical device' for regulatory application in biological evaluation according to ISO 10993-23. We conducted a round robin study to optimize and evaluate the performance of KeraSkin™ SIT for medical devices using KeraSkin™ Reconstructed Human Epidermis (RhE), which is developed and manufactured in Korea. This round robin study was performed to assess the transferability, reproducibility (within and between laboratories) and predictive capacity in 1 lead laboratory and 3 participating laboratories based on OECD Guidance Document 34. The predictive capacity, the results showed 83.3 % of sensitivity, 100 % of specificity and 91.6 % of accuracy. In conclusion, the results demonstrate that 'KeraSkin™ SIT for medical device' provides a robust test method for detecting irritant activity of medical device extracts and can be utilized for identifying low levels of potent irritants in medical device extracts. Therefore, it fulfills the requirements to be included as a 'me-too' test method to EpiDerm™ and SkinEthic™ skin irritation test in ISO 10993-23. • KeraSkin™ SIT for medical devices was developed as a ' me-too ' test method of skin irritation of medical devices. • The predictive capacity was 83.3 % of sensitivity, 100 % of specificity and 91.6 % of accuracy. • KeraSkin™ SIT for medical devices was fulfill the requirements in ISO 10993-23. • This round robin study (validation study) was leaded by KoCVAM. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fragmentation of simulated corium in sodium was studied using X-ray imaging system. • Fine fragments were generated, which found to solidify within short travel in sodium. • MFCI in sodium indicate a reduced potential for an energetic MFCI than that of water. • Absence of large size debris indicate favorable post-accident heat transfer in sodium. In case of a hypothetical core meltdown accident in Sodium cooled Fast Reactor (SFR), corium interacts with cold pool sodium and results in Molten Fuel Coolant Interaction (MFCI). During MFCI, the corium fragments and resultant debris settle on the core catcher as a bed and continue to generate decay heat. The size and state of fragmented debris play a crucial role in post-accident heat transfer. An experimental study has been undertaken to investigate the fragmentation of simulated corium in sodium using real-time X-ray imaging. Experiments were conducted by releasing ∼400 g of molten mixture of alumina and iron at ∼2400 °C into ∼4 kg of sodium at various temperatures. The fragmentation phenomenon was acquired using a digital flat panel detector and the captured images were subjected to image analysis to extract information on melt fragmentation. Post-experiment, fragmented debris was retrieved and subjected to sieve analysis to obtain characteristics towards assessing the dominant fragmentation mechanism. Experiments were also conducted with water for identifying key differences in the fragmentation and debris characteristics. Non-energetic fragmentation, generation of fine debris, and relatively minor sodium vaporization observed in the small-scale experiments present a reduced potential for energetic interaction in sodium than that of water. [ABSTRACT FROM AUTHOR]

• The shape of debris bed is important for the coolability of molten corium in severe accident. • The debris bed formation in DEFCON-S experiment is analyzed with the STAR-CCM+ code. • Relevant CFD models are established for the interaction between particles and fluids. • The behavior of stainless-steel particles is simulated with the discrete element model (DEM). • The shape of the debris bed obtained in CFD simulation is consistent with the experiment. In a severe accident of light-water reactor, molten corium can be formed and discharged into the reactor cavity. If the resulting debris bed is not adequately cooled, it could threaten the containment integrity by causing a molten core-concrete interaction. This study analyzes a non-heating debris bed formation experiment of DEFCON-S using the STAR-CCM+ code. Relevant CFD models are established to reflect the interaction between particles and fluids to describe the particle behavior and flow of fluids. The shape and size of debris bed are predicted through the CFD calculation. The rolling resistance becomes an important parameter in this simulation. The prediction with the default values of STAR-CCM+ forms a spread shape of particle bed compared to the experimental result. The shape of debris bed obtained with modified rolling resistance coefficients gives consistency with the DEFCON-S experiment, having a deviation in diameter of 4.6 % and a deviation in height of 3.8 %. [ABSTRACT FROM AUTHOR]

[Display omitted] • A Sustainable Biomimetic Electronic Skin. • Inspired by skin, first to use wood fiber skeleton to build a double-layer electronic skin structure. • For the first time, wood-based electronic skin with self-healing and anisotropic sensing will be developed. • Designed super-stretch elastomer using radiation manipulation and polymer cross-linking. Skin is a flexible and stretchable sensor composed of anisotropic dermis (DM) and repairable epidermis (EM). It repairs itself when damaged and has a multi-dimensional sensing system that can assist the body in performing some complex multi-dimensional movements. Inspired by skin, we utilized natural wood as the skeleton and for the first time designed a low-cost, double-layer structure wood-based electronic skin (wood-eskin). Simple chemical treatments were employed to directionally regulate the ray structure of natural wood and to enhance its porosity. Subsequently, physical freeze-thawing was employed to facilitate the formation of an entangled network structure between the PVA solution and the wood nanofibers. Wood-eskin with multi-dimensional sensing was obtained by further introducing ions by immersing in salt solution. In comparison to the majority of contemporary bionic e-skins, wood-eskin exhibits superior mechanical properties. Additionally, it is capable of performing complex deformations, such as bending and knotting. After fracture, wood-eskin can also repair itself and recover ∼94 % of its mechanical properties. The oriented arrangement of cellulose nanofiber channels gives wood-eskin a multidimensional sensing capability that can be used to monitor more complex body movements. The low-cost, biodegradable wood-eskin exhibits similar functionality to human skin, and its potential for biomedical and bionic robotics applications is considerable. [ABSTRACT FROM AUTHOR]

Caspase recruitment domain family member 14 (CARD14) and its variants are associated with both atopic dermatitis (AD) and psoriasis, but their mechanistic impact on skin barrier homeostasis is largely unknown. CARD14 is known to signal via NF-κB; however, CARD14-NF-κB signaling does not fully explain the heterogeneity of CARD14-driven disease. Here, we describe a direct interaction between CARD14 and MYC and show that CARD14 signals through MYC in keratinocytes to coordinate skin barrier homeostasis. CARD14 directly binds MYC and influences barrier formation in an MYC-dependent fashion, and this mechanism is undermined by disease-associated CARD14 variants. These studies establish a paradigm that CARD14 activation regulates skin barrier function by two distinct mechanisms, including activating NF-κB to bolster the antimicrobial (chemical) barrier and stimulating MYC to bolster the physical barrier. Finally, we show that CARD14-dependent MYC signaling occurs in other epithelia, expanding the impact of our findings beyond the skin. [Display omitted] • CARD14 signaling directly regulates MYC in keratinocytes to promote barrier homeostasis • Pathogenic genetic variants dysregulate CARD14-MYC signaling, promoting barrier dysfunction • Skin barrier function remains intact in the context of complete CARD14 deficiency • The CARD14-MYC mechanism may contribute to diseases beyond the epidermis The epithelial protein CARD14 canonically regulates NF-κB and is associated with atopic dermatitis and psoriasis. DeVore et al. report that CARD14 also regulates MYC signaling to influence barrier homeostasis—a mechanism altered by disease-associated genetic variants. This pathway may represent a potential therapeutic target in diseases of dysregulated barrier function. [ABSTRACT FROM AUTHOR]

This paper studies the transport of monoclonal antibodies through skin tissue and initial lymphatics, which impacts the pharmacokinetics of monoclonal antibodies. Our model integrates a macroscale representation of the entire skin tissue with a mesoscale model that focuses on the papillary dermis layer. Our results indicate that it takes hours for the drugs to disperse from the injection site to the papillary dermis before entering the initial lymphatics. Additionally, we observe an inhomogeneous drug distribution in the interstitial space of the papillary dermis, with higher drug concentrations near initial lymphatics and lower concentrations near blood capillaries. To validate our model, we compare our numerical simulation results with experimental data, finding a good alignment. Our parametric studies on the drug molecule properties and injection parameters suggest that a higher diffusion coefficient increases the transport and uptake rate while binding slows down these processes. Furthermore, shallower injection depths lead to faster lymphatic uptake, whereas the size of the injection plume has a minor effect on the uptake rate. These findings advance our understanding of drug transport and lymphatic absorption after subcutaneous injection, offering valuable insights for optimizing drug delivery strategies and the design of biotherapeutics. [Display omitted] [ABSTRACT FROM AUTHOR]

• Combined with the free-energy formula obtained by the calculated phase diagram and atomic diffusion determined by ab-initio molecular dynamics simulations, the phase-field simulations were carried out to investigate the evolution of molten U–Zr–O. • The diverse microstructural evolution pathway during the stratification process. Diverse intermediate morphologies could be observed during the evolution from different initial component distributions, even for the same averaged composition. • The agreement between simulation and experiments demonstrates the validity of the multi-scale simulations, which can capture the physical insights of the microstructural evolution of the corium pool. The morphological evolution of the molten corium is critical to the success of the "in-vessel retention" (IVR) strategy, which is of great significance for the safety of the nuclear industry under severe accidents. However, the direct observation of microstructural evolution by experiments is impossible in extreme conditions. Herein, a multi-scale simulation approach was employed to investigate the microstructural evolution and related mechanisms for the molten U–Zr–O ternary system. First, based on the reported calculated phase diagram, a simplified free energy formula describing a phase diagram of U–Zr–O was determined, where only liquid phases are focused. Then, the atomic diffusion coefficients were calculated by ab-initio molecular dynamics simulations. Based on such information, a homemade phase-field model was developed, which was coupled with Cahn–Hillard and Navier–Stokes equations. Accordingly, the microstructural evolution of molten U–Zr–O materials was systematically investigated. The results reveal that the evolution of the molten core was driven by both the decreasing free energy and gravity potential, accessing the final morphology of the system as a two-layer structure, including a metallic layer and an oxidized layer. Moreover, diverse intermediate morphologies could be observed from different initial component distributions, although their average compositions were identical. Finally, some intermediate simulated microstructural patterns agreed well with experimental observation, demonstrating the unstable structures captured by experiments and the validity of the simulations. The present study provides an effective approach to investigate the microstructural evolution of molten core and a guideline for optimizing the IVR strategy based on different morphologies in the corium. [ABSTRACT FROM AUTHOR]

Prinsepia utilis Royle, native to the Himalayan region, has a long history of use in traditional medicine for its heat-clearing, detoxification, anti-inflammatory, and analgesic properties. Oils extracted from P. utilis seeds are also used in cooking and cosmetics. With the increasing market demand, this extraction process generates substantial industrial biowastes. Recent studies have found many health benefits with using aqueous extracts of these biowastes, which are also rich in polysaccharides. However, there is limited research related to the reparative effects of the water extracts of P. utilis oil cakes (WEPUOC) on disruptions of the skin barrier function. This study aimed to evaluate the reparative efficacy of WEPUOC in both acute and chronic epidermal permeability barrier disruptions. Furthermore, the study sought to explore the underlying mechanisms involved in repairing the epidermal permeability barrier. Mouse models with induced epidermal disruptions, employing tape-stripping (TS) and acetone wiping (AC) methods, were used. The subsequent application of WEPUOC (100 mg/mL) was evaluated through various assessments, with a focus on the upregulation of mRNA and protein expression of Corneocyte Envelope (CE) related proteins, lipid synthase-associated proteins, and tight junction proteins. The polysaccharide was the major phytochemicals of WEPUOC and its content was determined as 32.2% by the anthranone-sulfuric acid colorimetric method. WEPUOC significantly reduced transepidermal water loss (TEWL) and improved the damaged epidermal barrier in the model group. Mechanistically, these effects were associated with heightened expression levels of key proteins such as FLG (filaggrin), INV (involucrin), LOR (loricrin), SPT, FASN, HMGCR, Claudins-1, Claudins-5, and ZO-1. WEPUOC, obtained from the oil cakes of P. utilis , is rich in polysaccharides and exhibits pronounced efficacy in repairing disrupted epidermal barriers through increased expression of critical proteins involved in barrier integrity. Our findings underscore the potential of P. utilis wastes in developing natural cosmetic prototypes for the treatment of diseases characterized by damaged skin barriers, including atopic dermatitis and psoriasis. [Display omitted] • The water extract of Prinsepia utilis oil cakes (WEPUOC) can repair epidermal barriers. • WEPUOC upregulates corneocyte envelope protein expression in the stratum corneum. • WEPUOC upregulates the expression of lipid synthases among corneocytes. • WEPUOC enhances the expression of tight junction proteins. [ABSTRACT FROM AUTHOR]

Melanoma is a type of tumor skin with high metastatic potential. Reconstructed human skin, development for pre-clinic assay, are make using primary human cells, but with same limitations. The aim this study was to characterize a cell culture model, with structure similar to human skin containing melanoma cells entirely from cell lines. Reconstructed skin with melanoma were development using human fibroblasts (MRC5), human epidermal keratinocytes (HaCat), and human melanoma (SK-MEL-28) embedded in collagen type I. The structure was characterized by hematoxylin–eosin stained, as well as points of melanoma cell invasion, which was associated with activity of MMPs (MMP-2 and MMP-9) by zymographic method. Then, the gene expression of the target molecular mechanisms involved in melanoma progression were evaluated. Here, the model development showed a region epidermis organized and separated from the dermis, with fibroblast cells confined and melanoma cells form delimited area invasion. MMP-2 and MMP-9 were identified during of cell culture and gene expression of BRAF, NRAS, and Vimentin was confirmed. The proposed model provides one more opportunity to study in vitro tumor biology of melanoma and also to allows the study of new drugs with more reliable results then whats we would find in vivo. • The artificial model of human skin with melanoma has epidermal and dermal regions. • In the model of human skin, melanoma cells invaded the extracellular matrix. • The invasion of melanoma cells was likely with activity of MMPs (MMP-2 and MMP-9). • Melanoma cells increased the gene expression of NRAS, BRAF and Vimentin. [ABSTRACT FROM AUTHOR]

Application of 'omics' technology, and advances in in vitro methods for studying the growth of Fasciola hepatica, have highlighted the central role of migrating neoblasts in driving forward development and differentiation towards the adult-like form. Neoblast populations present molecular heterogeneity, morphological variation and changes associated with recruitment of these stem cells into their final tissue locations. However, terminal differentiation towards function, has received much less attention than has been the case for the free-living Platyhelminths. An actively replicating neoblast population, comprising cells with heterochromatic nuclei consistent with regulation of gene expression, has been identified in the parenchyma of juvenile Fasciola gigantica migrating in the liver of experimentally infected mice. In some of these cells, early cytoplasmic differentiation towards myocyte function was noted. Neoblasts have also been identified close to, and incorporated in, the subtegumental zone, the gastrodermis and the excretory ducts. In these locations, progressive morphological differentiation towards terminal function has been described. This includes the appearance of specific progenitors of type-1, type-2 and type-3 tegumental cells, the latter possibly contributing to tegumental spine development. 'Cryptic' surface molecular differentiation is postulated to account for recognition and 'docking' of migrating neoblasts with their final site for terminal differentiation. • Migrating neoblasts have been identified in juvenile Fasciola gigantica in mice. • Neoblasts also occur in the subtegument, gastrodermis and excretory ducts. • Morphological differentiation towards terminal function has been described. • Differentiating type-3 tegumental cells may contribute to tegumental spines. • 'Cryptic' surface molecular differentiation may facilitate neoblast localisation. [ABSTRACT FROM AUTHOR]

There are feedforward and feedback loops along the microbiota–root–shoot axis to maintain plant growth or defense under environmental stresses. Here, we highlight a reciprocal interaction between the endodermis and the plant–bacterial community, which stabilizes the diffusion barriers to maintain nutrient homeostasis under nutritional stress. [ABSTRACT FROM AUTHOR]

Various approaches have been explored to study skin biology, including the use of stem cells. Mesenchymal stem cells (MSCs) from the umbilical cord can be safely and easily obtained; however, a simple strategy to monitor their differentiation is essential. Involucrin is a marker of keratinocyte differentiation, and its promoter (pINV) directs stratum-specific expression of this protein. We designed a reporter system containing EGFP under the control of pINV to assess MSC transdifferentiation into keratinocytes. The functional sequence of pINV was inserted into a lentiviral vector, producing LeGO-GpINV. MSCs were transduced with LeGO-GpINV and induced to transdifferentiate into keratinocytes under cultivation with keratinocyte serum-free medium. MSC transdifferentiation was confirmed by morphological changes and by the expression of epidermal markers by flow cytometry, quantitative PCR, Western blot and the activity of epidermal kallikreins 5, 6 and 7. After 14 days of transdifferentiation, MSCs transduced with LeGO-GpINV showed an increase in EGFP fluorescence and expressed CK10, CK14, involucrin and filaggrin. There was also an increase in kallikrein activity. This reporter system allowed us to temporally assess epidermal differentiation, simultaneously with involucrin expression, opening possibilities for the in vivo study of skin biology and in regenerative medicine. • Involucrin promoter as a tool to follow epidermal differentiation. • A GFP-based lentiviral vector can be used to monitor MSC epidermal differentiation. • MSC induced to epidermal fate express GFP under involucrin promoter control. [ABSTRACT FROM AUTHOR]

The balance between stem cell renewal and differentiation is determined by the interplay between intrinsic cellular controls and extrinsic factors presented by the microenvironment, or 'niche'. Previous studies on cultured human epidermis have utilised suspension culture and restricted cell spreading to investigate regulation of differentiation in single keratinocytes. However, keratinocytes are typically adherent to neighbouring cells in vivo. We therefore developed experimental models to investigate the combined effects of cell-ECM adhesion and cell-cell contact. We utilized lipid-modified oligonucleotides to form clusters of keratinocytes which were subsequently placed in suspension to induce terminal differentiation. In this experimental model cell-cell contact had no effect on suspension-induced differentiation of keratinocytes. We next developed a high-throughput platform for robust geometrical confinement of keratinocytes to hexagonal ECM-coated islands permitting direct cell-cell contact between single cells. As in the case of circular islands, differentiation was stimulated on the smallest single hexagonal islands. However, the percentage of involucrin-positive cells on small bowtie islands was significantly lower than on single islands, demonstrating that cell-cell contact reduced differentiation in response to decreased substrate adhesion. None of the small bowtie islands contained two involucrin-positive cells. Rather, if one cell was involucrin-positive the other was involucrin-negative. This suggests that there is intrinsic asymmetry in the effect of cell-cell contact in decreasing differentiation. Thus, our reductionist approaches provide new insights into the effect of the niche on keratinocyte differentiation. Stem cell behaviour is regulated by a combination of external signals, including the nature of the adhesive substrate and cell-cell interactions. An understanding of how different signals are integrated creates the possibility of developing new biomaterials to promote tissue regeneration and broaden our understanding of skin diseases such as eczema and psoriasis, in which stem cell proliferation and differentiation are perturbed. In this study we have applied two methods to engineer intercellular adhesion of human epidermal stem cells, one involving lipid-modified DNA and the other involving hexagonal micropatterns. We show that the effect of cell-cell adhesion depends on cell-substrate adhesion and uncover evidence that two cells in equivalent environments can nevertheless behave differently. [Display omitted] [ABSTRACT FROM AUTHOR]

Heavy metals like cadmium (Cd) are a serious threat for living organisms due to increased global environmental pollution. Aloe ferox Mill. is a very important species of the genus Aloe , especially from a medical point of view, because it is a source of biologically active substances and it is often used in the traditional medicine. Since the knowledge about the effect of heavy metals, like Cd on growth of Aloe species is scarce, this study showed the effect of Cd on anatomical, morphological and physiological properties of this important medicinal plant species. We found that Cd affected the leaf morphology and decreased biomass of the aboveground plant part. Cd also affected cuticle deposition and increased the number of stomata in the abaxial and adaxial epidermis of leaves. Roots treated with Cd showed lower lignification and decreased level of membrane lipids peroxidation than control roots. Cadmium concentration was the highest in the roots; however, relatively high portion of Cd is being translocated to the leaves. This might be dangerous as Aloe is well known medicinal plant with content of active secondary metabolites mainly in the leaves. • Cd reduced leaf size and thickness of A. ferox plants. • Cd increased stomatal density and affected cuticle deposition in A. ferox leaves. • Root lignification and lipid peroxidation after Cd treatment decreased. • Cd showed more prominent toxic effect on leaves than roots of A. ferox. [ABSTRACT FROM AUTHOR]

Traveling-wave optical coherence elastography (OCE) is a promising technique to measure the stiffness of biological tissues. While OCE has been applied to relatively homogeneous samples, tissues with significantly varying elasticity through depth pose a challenge, requiring depth-resolved measurement with sufficient resolution and accuracy. Here, we develop a broadband Rayleigh-wave OCE technique capable of measuring the elastic moduli of the 3 major skin layers (epidermis, dermis, and hypodermis) reliably by analyzing the dispersion of leaky Rayleigh surface waves over a wide frequency range of 0.1–10 kHz. We show that a previously unexplored, high frequency range of 4–10 kHz is critical to resolve the thin epidermis, while a low frequency range of 0.2–1 kHz is adequate to probe the dermis and deeper hypodermis. We develop a dual bilayer-based inverse model to determine the elastic moduli in all 3 layers and verify its high accuracy with finite element analysis and skin-mimicking phantoms. Finally, the technique is applied to measure the forearm skin of healthy volunteers. The Young's modulus of the epidermis (including the stratum corneum) is measured to be ∼ 4 MPa at 4–10 kHz, whereas Young's moduli of the dermis and hypodermis are about 40 and 15 kPa, respectively, at 0.2–1 kHz. Besides dermatologic applications, this method may be useful for the mechanical analysis of various other layered tissues with sub-mm depth resolution. To our knowledge, this is the first study that resolves the stiffness of the thin epidermis from the dermis and hypodermis, made possible by using high-frequency (4 – 10 kHz) elastic waves and optical coherence elastography. Beyond the skin, this technique may be useful for mechanical characterizations of various layered biomaterials and tissues. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Dermal microdialysis (dMD) permits the investigation of cutaneous pharmacokinetics (cPK) for topical dermatological drug products (TDDP). dMD involves probe implantation into the dermis and a sample collection system that restricts subjects' movements for the experimental duration. A truncated dose-duration, by TDDP removal at predetermined time-points, may help to adequately characterize the cPK in a relatively short time. The goals of this study were to: assess and compare the dose-duration effect on the dermal exposure of metronidazole (MTZ) containing TDDPs; and characterize MTZ dermal elimination following TDDP application and direct dermal delivery of MTZ utilizing a retrodialysis/microdialysis approach that we termed "dermal infusion." MTZ cream and gel were applied on three Yucatan mini-pigs for dose-durations of 6-hr, 12-hr, or 48-hr. The gel's dermal exposure was similar among the three dose-durations. Conversely, at the 6-hr dose-duration, the cream's dermal exposure was significantly lower than other cream dose-durations while also comparable to the gel. In comparison, the 12-hr and 48-hr cream exposures were not significantly different. Terminal-phase half-live differences between the MTZ TDDP's and dermal-infusion indicate flip/flop cPK. Truncating topical dose-duration may provide a valuable strategy to reduce experimental duration; however, dose-duration must be carefully selected if the goal is to discriminate between formulations. [ABSTRACT FROM AUTHOR]

Age-related thinning and reduced cell proliferation in the human epidermis are associated with the accumulation of senescent cells and decreases in the number and function of epidermal stem cells. This study examined the expression of INHBA/Activin-A in human epidermis and expression differences with age, and the effect of Activin-A on epidermal stem/progenitor cells. Immunohistochemical staining was used to analyze age-related changes in the expression of INHBA/Activin-A in the epidermal tissue of young and old subjects. Epidermal INHBA/Activin-A expression levels, epidermal morphology, and the number of epidermal stem/progenitor cells or proliferating cells were investigated using older abdominal skin samples. The effects of Activin-A on the development of a three-dimensional (3D) reconstructed epidermis and cell proliferation were also assessed. INHBA/Activin-A expression levels in the human epidermis increased with age, although they varied among individuals. In the epidermis of older abdominal skin samples, INHBA/Activin-A expression levels negatively correlated with epidermal thickness, the rete ridge depth and the interdigitation index. The proportion of epidermal stem/progenitor cells and proliferating cells decreased with increases in INHBA/Activin-A expression levels. Activin-A had no effect on the differentiation of keratinocytes in the 3D-reconstructed epidermis; however, thinning of the 3D epidermis was noted. Moreover, the addition of Activin-A inhibited the proliferation of epidermal stem/progenitor cells in a concentration-dependent manner. Age-related increased in INHBA/Activin-A expression levels were observed in the human epidermis, and may contribute to epidermal thinning and decreases in the number of epidermal stem/progenitor cells and proliferative activity. • The expression of INHBA/Activin-A in human epidermis increased with age. • Reduced epidermal stem/progenitor cells in human epidermis highly expressing INHBA. • Reduced proliferating cells in human epidermis highly expressing INHBA. • Activin-A suppresses the proliferation of epidermal stem/progenitor cells. [ABSTRACT FROM AUTHOR]