Epidermal Shedding Research Articles

Medical nutrition therapy in hospitalized patients with pemphigus vulgaris

Dysphagia due to involvement of the oral, pharyngolaryngeal, and esophageal mucosa and increased catabolism due to epidermal shedding can contribute to a decline in nutritional status in pemphigus vulgaris (PV) patients. On the other hand, decreased lean body mass is associated with immune system impairment, increased risk of infection, and delayed wound healing in PV patients, therefore, nutritional screening and assessment are necessary. Medical nutritional therapy in PV patients aims to overcome the metabolic response to the insults, prevent further malnutrition, modulate the immune system, and accelerate wound healing process. An aggressive nutritional support to minimize protein loss during the phase of mucocutaneous lesion healing is needed in patients with PV. Aside from macronutrient adequacy, micronutrients including vitamin A supplementation can be considered to accelerate wound healing process. Medical nutritional therapy including provision of adequate macronutrients, micronutrients, addressing dehydration and electrolyte imbalances should be the cornerstone of multidisciplinary treatment in PV patients.

A Case Study of Generalized Eczema Induced by Ginkgolide Injection

Objective: To analyze the clinical characteristics of adverse skin reactions (ADRs) caused by ginkgolide injection, and to provide reference for the post-marketing safety study of ginkgolide injection. Methods: By participating in the treatment of a patient with suspected adverse skin reactions caused by ginkgolide injection, The patient was given target ginkgolide injection 50mg intravenously once a day for two consecutive days due to cerebral infarction. Six days after drug withdrawal, the patient developed a rash on the buttocks, and then the rash quickly spread to the whole body, resulting in skin lesions with exudation tendency, itchy skin and extensive epidermal shedding. Combined with clinical medication and the clinical characteristics of this adverse reaction, the causes and mechanisms of adverse reactions caused by ginkgolide injection were analyzed from the ingredients of ginkgolide injection and the adverse reaction reports of ginkgolide extract. Consults: The adverse reaction was analyzed as severe skin allergy caused by ginkgolide injection. After oral administration of ebastine, injection of calcium gluconate and vitamin C, and topical dehumidification and itching-relieving ointment, the skin lesions basically healed after 2 weeks. Conclusions: Cases of skin allergic reactions caused by ginkgolide injection have been reported, but clinical trials on the safety of ginkgolide injection still lack the content of post-marketing safety studies. This adverse reaction is a detailed case analysis, in order to provide reference for the content of post-marketing safety of ginkgolide injection.

Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging

ObjectiveThe epidermal barrier is renewed by the activation, proliferation, and differentiation of keratinocyte stem cells after injury and aging impedes this repair process through undefined mechanisms. We previously identified a gene signature of metabolic dysfunction in aged murine epidermis, but the precise regulators of epidermal repair and age-related growth defects are not well established. Aged mouse models as well as mice with conditional epidermal loss of the metabolic regulator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1α) were used to explore the cellular pathways which control skin repair after injury and stress. MethodsAged mice or those with epidermal Pgc-1α deletion (epiPgc-1α KO) and young or Pgc1afl/fl controls were subjected to wound injury, UVB exposure or the inflammatory agent TPA. In vivo and ex vivo analyses of wound closure, skin structure, cell growth and stem cell differentiation were used to understand changes in epidermal re-growth and repair resulting from aging or Pgc-1α loss. ResultsAging impairs epidermal re-growth during wound healing and results in lower expression of Pgc-1α. Mice with conditional deletion of epidermal Pgc-1α exhibit greater inflammation- and UVB-induced cell differentiation, reduced proliferation, and slower wound healing. epiPgc-1α KO mice also displayed reduced keratinocyte NAD+ levels, shorter telomeres, and greater poly ADP-ribosylation, resulting in enhanced stress-stimulated p53 and p21 signaling. When NAD+ was reduced by Pgc-1α loss or pharmacologic inhibition of NAD+ synthesis, there was reduced stress-induced proliferation, increased differentiation, and protection against DNA damage via enhanced epidermal shedding. Similarly, aged mice exhibit disrupted epidermal NAD+ homeostasis and enhanced p53 activation, resulting in p21 growth arrest after wounding. NAD+ precursor treatment restores epidermal growth from old skin to that of young. ConclusionsOur studies identify a novel role for epidermal Pgc-1α in controlling epidermal repair via its regulation of cellular NAD+ and downstream effects on p53-driven growth arrest. We also establish that parallel mechanisms are evident in aged epidermis, showing that NAD+ signaling is an important controller of physiologic skin repair and that dysfunction of this pathway contributes to age-related wound repair defects.

Immunolocalization of the EDWM-Protein Indicates a Matrix Role in Cornification of Lizard Epidermis

During epidermal differentiation in the scales of lizards and snakes, from the basal layer beta- and later alpha-keratinocytes are generated to form beta-and alpha-corneous layers. In the lizard Anolis carolinensis, minor proteins derived from the EDC (Epidermal Differentiation Complex) are added to the main constituent proteins, IFKs (Intermediate Filament Keratins) and CBPs (Corneous Beta Proteins, formerly indicated as beta keratins). One of these proteins that previous studies showed to be exclusively expressed in the skin, EDWM (EDC protein containing high GSRC amino acids) is rich in cysteine and arginine, amino acids that form numerous –S–S– and electro-static chemical bonds in the corneous material. Light and electron microscopy immunolbeling for EDWM show a diffuse localization in differentiating beta-cells and in some alpha-cells, in particular those of the clear-layer, involved in epidermal shedding. The study suggests that EDWM may function as a matrix protein that binds to IFKs and CBPs, contributing to the formation of the specific corneous material present in beta- and alpha-corneous layers. In particular, its higher immunolocalization in the maturing clear layer indicates that this protein is important for its differentiation and epidermal shedding in A. carolinensis and likely also in other lepidosaurian reptiles.

Cell wall structural changes lead to separation and shedding of biofouled epidermal cell wall layers by the brown alga Ascophyllum nodosum.

Marine plants control the accumulation of biofouling organisms (epibionts) on their surfaces by various chemical and physical means. Ascophyllum nodosum is a perennial multicellular brown alga known to shed patches of epidermal material, thus removing epibionts and exposing unfouled surfaces to another cycle of colonization. While surface shedding is documented in multiple marine macroalgae, the cell and developmental biology of the phenomenon is almost unexplored. A previous investigation of Ascophyllum not only revealed regular cycles of epibiont accumulation and epidermal shedding but also stimulated the development of methods to detect the corresponding changes in epidermal (meristoderm) cells that are reported here. Confocal laser scanning microscopy of cell walls and cytoplasm fluorescently stained with Solophenyl Flavine 7GFE (Direct Yellow 96) and the lipophilic dye Rhodamine B (respectively) was combined with light and electron microscopy of chemically fixed or freeze-substituted tissues. As epibionts accumulated, epidermal cells generated thick, apical cell walls in which differentially stained central layers subsequently developed, marking the site of future cell wall separation. During cell wall separation, the outermost part of the cell wall and its epibionts plus the upper parts of the anticlinal walls between neighboring cells detached in a layer from multiple epidermal cells, exposing the remaining inner part of the cell wall to new colonizing organisms. These findings highlight the dynamic nature of apical cell wall structure and composition in response to colonizing organisms and lay a foundation for further investigations on the periodic removal of biofouling epibionts from the surface of Ascophyllum fronds.

3D-QSAR, HQSAR, molecular docking, and new compound design study of 1,3,6-trisubstituted 1,4-diazepan-7-ones as human KLK7 inhibitors

The skin is an important barrier against environmental factors. Foregoing studies has shown that human KLK7 is a protease which promoted epidermal shedding, affected the epidermal barrier and increased the risk of atopic dermatitis. In this study, the structure and activity relationship of 40 human KLK7 inhibitors was explored by three-dimensional quantitative structure–activity relationship (3D-QSAR) and hologram quantitative structure–activity relationship (HQSAR). 3D-QSAR including comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis fields (CoMSIA), and Topomer comparative molecular field analysis (Topomer CoMFA). From the data we got, the 3D-QSAR models (CoMFA with q2 = 0.755, r2 = 0.994; CoMSIA with q2 = 0.602, r2 = 0.980; Topomer CoMFA with q2 = 0.644, r2 = 0.929) and the HQSAR model (q2 = 0.717, r2 = 0.950) had a good predictability. Molecular docking was used to reveal the binding mode between the inhibitors and KLK7 protein further. 3D-QSAR, HQSAR, and molecular docking results also provided guidance for discovering new human KLK7 inhibitors. Finally, 13 new compounds were designed as potential human KLK7 inhibitors, and the predicted activity values showed an effective inhibition on human KLK7.

Zhibaidihuang Decoction Ameliorates Cell Oxidative Stress by Regulating the Keap1-Nrf2-ARE Signalling Pathway.

Zhibaidihuang decoction (ZBDHD) is a Chinese herbal formula, which is used in Chinese traditional medicine to treat symptoms of Yinxuhuowang (Yin deficiency and high fire) syndrome. This study elucidates the mechanism of ZBDHD on oral ulcers, one Yinxuhuowang syndrome. Simultaneously, some ingredients in ZBDHD were found and identified by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A Ganjiangfuzirougui decoction- (GJD-) induced Yinxuhuowang syndrome SD rat model was used to demonstrate the efficiency of ZBDHD treatment. The oral mucosa of rat in the GJD group, stained with hematoxylin and eosin (H&E), showed epidermal shedding and inflammatory cell infiltration. And an alleviation efficiency of ZBDHD in GJD-induced pathological changes in the oral mucosa could be obtained. ZBDHD treatment restored the GJD-induced imbalance of metabolites, which were choline, glycocholic acid, and palmitoyl-L-carnitine (PALC). GJD stimulated the expression of NF-κB. And the overexpressed of NF-κB in mucosa of rat in the GJD group could be inhibited by ZBDHD treatment. Simultaneously, the optimal efficiency of ZBDHD treatment on the cellular ATP content, oxygen consumption rate (OCR), and superoxide dismutase (SOD) concentration was evaluated, in vitro assay. Compared to the control cells, the ATP content, OCR, and SOD activity in the ZBDHD-treated cells were significantly higher. For the mechanisms study, seven cytokines were screened with a Dual-Luciferase Reporter gene assay. In the ARE assay, the luciferase signal was stimulated significantly by ZBDHD. In cells, the transcription of nrf2, maf, and keap1, which were related to the ARE pathway, was elevated by ZBDHD treatment. Our study demonstrated that high-dose GJD could lead to Yinxuhuowang syndrome, such as oral ulcers, and the imbalance in serum metabolites. And ZBDHD can improve oral cell inflammation and the imbalance of metabolism by inhibiting NF-κB and enhancing the activity of the ARE signalling pathway to ameliorate oxidative stress in the cell. This study provides a theoretical basis for the clinical application of ZBDHD.

Structure guided drug design to develop kallikrein 5 inhibitors to treat Netherton syndrome

The connection between Netherton syndrome and overactivation of epidermal/dermal proteases particularly KLK5 has been well established. To treat sufferers of this severe condition we wished to develop a topical KLK5 inhibitor in order to normalise epidermal shedding and reduce the associated inflammation and itching. In this paper we describe structure-based optimisation of a series of brightly coloured weak KLK5 inhibitors into colourless, non-irritant molecules with good KLK5 activity and selectivity over a range of serine proteases.

Epidermal shedding in Ascophyllum nodosum (Phaeophyceae): seasonality, productivity and relationship to harvesting

:Epidermal shedding, a process that effectively controls epiphyte accumulation on certain long-lived macroalgae, was quantified weekly for over 1 year in a population of Ascophyllum nodosum from Nova Scotia. About 25% of the frond epidermis is shed per week and for at least 9 months of the year, this shedding occurred in population-level cycles of skin shedding followed by reaccumulation of epiphytes. Using a geometric model based on cross-sectional area of branches assigned to one of four size categories, we determined that about 1% of frond biomass is shed during each monthly cycle. Taking into account the differences in frond architecture at 10 sites from around Nova Scotia, an estimated 10% of vegetative frond biomass enters coastal waters each year solely as a result of epidermal shedding. This natural contribution to coastal detritus amounts to about 2 t ha−1 of Ascophyllum beds in Lobster Bay, the primary harvest region for Ascophyllum in Nova Scotia. This is a significant and previously unconsidered addition to the environmental impact of the annual harvest of over 20 t ha−1 that is reported by industry from this area. These data form part of a wider assessment of the impact of the commercial harvest of Ascophyllum on biomass removal from coastal detrital food webs.

Cell Division in the Absence of Mitosis: The Unusual Case of the Fucoid Ascophyllum nodosum (L.) Le Jolis (Phaeophyceae)

Fluorescence and electron microscopy were used to examine epidermal shedding in the fucoid alga, Ascophyllum nodosum. Mature meristoderm cells are ca. 50-100 x 30-40 and highly polarized, with a single nucleus and chloroplasts near the base of the cell. Nuclei in these cells undergo mitosis when they are dividing to form a new cortical cell towards the middle of the frond, or anticlinal divisions as part of frond elongation. However, cytokinesis also occurs regularly in these cells when a new periclinal wall is deposited at about 30% of the cell length from the apical end. The newly formed distal cells are anucleate and without chloroplasts. Following cytokinesis the tangential walls then break at the thinnest point. The whole process is synchronous in adjoining epidermal cells across large areas of the frond surface, and this layer dehisces from the thallus. This is the only known plant or algal system in which cytokinesis regularly occurs in the absence of mitosis. We consider this process a novel form of programmed cell death.

Epidermal structure of normal and regenerating skin of the agamine lizard Physignatus lesueurii (McCoy, 1878) with emphasis on the formation of the shedding layer

Comparative study of the epidermis of lepidosaurian reptiles helps us to understand the formation of the shedding complex which determines epidermal shedding. The present ultrastructural study has analyzed the complete sequence of epidermal differentiation in the agamine lizard Physignatus lesueurii from 1 to 80 days post-hatching. Beneath a β-layer 20–40 layers of cells with an α-pattern of keratinization are produced, starting from narrow cells (mesos-like) followed gradually by typical thicker α-cells. At 80 days post-hatching an α-layer is still forming and the first epidermal shedding has still to take place. The differentiation of a shedding complex has been studied on the epidermis at 38 and 64 days of tail regeneration. Beneath the superficial regenerating (wound) epidermis, cells of the clear layer contain a meshwork of coarse and fibrous filaments which appear to turn into large keratohyalin-like granules. This extensive cytoskeleton may determine the progressive hardening of clear cells that function as a template for the formation of the large microornamentations of the underlying layer, a process that might be generalized for the genesis of microornamentations in all lepidosaurian reptiles. The microornamentations in Physignatus have a honey-comb pattern and are produced by the fusion between ‘oberhautchen” and β-cells.

Presence of acid phosphatase in the epidermis of the regenerating tail of the lizard (Podarcis muralis) and its possible role in the process of shedding and keratinization

AbstractThe activity and distribution of the lysosomal marker enzyme acid phosphatase have been studied in the epidermis during tail regeneration in the lizard Podarcis muralis. This study gives information both on the mechanism of separation of the old from the new epidermal generation and on the involvement of lysosomes in β‐ and α‐keratinization in lepidosaurians. The biochemical analysis shows that the activity of acid phosphatase was higher in the regenerating tail than in the normal tail until the stage of skin shedding at around 25–30 days post‐amputation. The enzyme was present in keratinizing layers of epidermis, and particularly in the shedding layer. The shedding layer followed the outline of the regenerating scales beneath the wound in the epidermis showing that lysosomal enzymes are involved in epidermal shedding. The ultrastructural study showed that acid phosphatase was initially localized within the lysosomes but, with the progress of differentiation, it also appeared free within the cytoplasm of the cornifying cells of the shedding complex and of the β‐keratinizing cells, and in the intercellular space among them. The role of lysosomal enzymes in the shedding process and their involvement in the mechanism of β‐keratinization is discussed. While the process of β‐keratinization has an intracellular and extracellular localization of acid phosphatase, the process of α‐keratinization shows that most acid phosphatase is localized within the cell. Lysosomes and mesos granules containing acid phosphatase were concentrated in the cytoplasm of differentiating mesos cells. Some mesos granules later discharged their contents into the extracellular space. The α‐layer was partially formed in proximal regenerated scales around 30 days post‐amputation. Lysosomes appeared to concentrate within pre‐keratinizing cells of the α‐keratin layer and little reactivity was seen extracellularly.

Skin Abnormalities in Mice Transgenic for Plasminogen Activator Inhibitor 1: Implications for the Regulation of Desquamation and Follicular Neogenesis by Plasminogen Activator Enzymes

Plasminogen activator enzymes have been implicated in the regulation of growth, migration, and differentiation which occur continually in normal epidermis and cyclically in the hair follicle. To elucidate further the importance of plasminogen activation in epidermal physiology, studies were conducted using mice transgenic for human plasminogen activator inhibitor 1 (PAI-1). The epidermis of the newborn (4-7 days) transgenic mice was flaky and showed delayed hair growth compared to that of their control littermates. Histologic analyses revealed a greatly thickened stratum corneum in the transgenics. By 2 weeks after birth, no differences in epidermal morphology were apparent between transgenic and control littermates. Using in situ hybridization, immunocytochemistry, and in situ reverse zymography techniques, epidermal PAI-1 expression was correlated temporally with the aberrant epidermal morphology. These data implicate plasminogen activator activity in the regulation of epidermal shedding and follicular neogenesis.

Neutral Lipid Storage Disease With Ichthyosis

Although the link between epidermal lamellar body lipids and stratum corneum barrier function is well established, a role for lamellar body lipids in desquamation remains unproved. We examined skin biopsy material from three family members of a Palestinian kindred with a multisystem disorder of altered lipid metabolism, ichthyosis, and deposition of fat droplets in multiple tissues (Chanarin-Dorfman syndrome, neutral lipid storage disease). Thin-section and freeze-fracture ultrastructural studies revealed a distinctive lamellar body abnormality: multilaminated spherules that distorted and displaced the normal internal disk structure of these organelles. Whereas these spherules remained interspersed with secreted lamellar body contents within the intercellular spaces of the outer epidermis, at the stratum granulosum-stratum corneum interface they apparently dispersed into electron-lucent "slits." These studies therefore provide strong support for the concept that lamellar body-derived lipids influence stratum corneum desquamation and further suggest that abnormalities of neutral lipid-alkane metabolism influence normal epidermal shedding.

Cutaneous water loss and the epidermal shedding cycle in the tokay ( Gekko gecko) (Lacertilia, reptilia)

1. 1. The relationship between cutaneous water loss (CWL) and the squamate shedding cycle has not been investigated previously. 2. 2. We measured CWL in the tokay by compartmentalized chamber and capsule techniques throughout the shedding cycle and related the values to changes in epidermal morphology. 3. 3. CWL is high during shedding, decreases thereafter, and reaches lowest levels during the resting stage and the early renewal phase. CWL increases thereafter until the shed occurs. 4. 4. Analysis of this pattern shows that it supports the thesis that the alpha layer of the tokay epidermis is the main permeability barrier.