Epidermal Thinning Research Articles

Growth media change Eisenia fetida epithelium thickness: implications for improving earthworm welfare in vermicomposting systems.

Because the earthworm tegument represents their first barrier against environmental aggressions, we hypothesised that substrate-induced changes in earthworm growth would also alter the morphology of this protective layer. Therefore, a histological and morphometric study was performed on Eisenia fetida specimens that have been grown in five different organic residues: cow manure, horse manure, grape marc, coffee grounds, and a mixture of coffee grounds and cooking oil. The results showed that, across all treatments, both cuticle and epidermis were significantly thicker in the pre-clitellar region than after the clitellum, attributed to the fact that the former region is responsible for breaking up the soil. Notably, the growing media significantly altered the thickness of these two integumentary layers, and the greatest thicknesses were measured in grape marc and in the mixture coffee grounds + cooking oil, which makes them suitable organic residues for vermicomposting. By contrary, a significant epidermal thinning was observed when growing on coffee grounds alone, clearly indicating that it is a hostile environment for earthworms. Overall, these results reveal that tegument thickness can be used not only as a trait indicator of substrate quality but also of earthworm welfare, and it should be integrated in future toxicity assessment and captive breeding guidelines.

Surgical pearl: Use of micropore tape for easy harvestation and transfer of suction blister epidermal graft

Epidermal graft produced by suction is useful in treating vitiligo. However, it is very difficult to handle thin, flimsy, and translucent epidermis due to its in-curling and wrinkling properties. This is due to the hemispherical blister roof surface area which is twice its circular base. The correction of the epidermal surface and its resizing is a cumbersome and time-consuming task during epidermal grafting. To combat these problems, the blister roof is patched with micropore adhesive tape as a novel technique for harvestation and transfer of the suction blister graft.

Novel biophysical skin biomarkers discriminate topical anti‐inflammatory treatments based on their potential for local adverse effects

AbstractBackgroundTopical corticosteroids (TCS) are efficacious treatments for inflammatory skin conditions, however, there is a risk of adverse effects; understanding how best to use these treatments is an unmet research priority shared by patients and healthcare professionals.ObjectivesTo develop non‐invasive biomarkers of local adverse effects to facilitate the optimisation of topical therapy.MethodsAn observer‐blind randomised within‐subject controlled trial in atopic dermatitis patients was undertaken (NCT04194814) comparing betamethasone valerate 0.1% cream (BMV) to a non‐steroidal anti‐inflammatory treatment, crisaborole 2% ointment (CRB). Participants underwent 4 weeks twice‐daily treatment with CRB on one forearm and BMV on the other (left/right randomised). Skin properties were assessed on days 1, 15, 29 of treatment and again on day 57, including imaging of skin microstructure using Optical Coherence Tomography (OCT) and Attenuated Total Reflectance (ATR)‐Fourier Transform Infrared (FTIR) spectroscopic assessment of stratum corneum molecular structure. The primary outcome was the difference in the change in epidermal thickness from days 1 to 29.ResultsThirty‐seven participants received the first dose, of which 32 completed the study (all 37 were included in the analysis). Pathologic epidermal thinning at day 29 was significantly greater (p < 0.0001) at sites treated with BMV (−31.66; 95% confidence interval: −35.31, −28.01 µm) compared to CRB (−13.76; −17.42, −10.10 µm). From a panel of exploratory biomarkers, superficial plexus depth and stratum corneum carboxyl group levels had the greatest ability to discriminate the effects of the TCS treatment (p < 0.0001).ConclusionsBMV induced 2.3x more pathologic epidermal thinning than CRB after 4 weeks of treatment, suggesting that CRB may be more appropriate for longer‐term, proactive‐based, treatment strategies where the risks of adverse effects are greatest. By monitoring treatment effects using OCT and ATR‐FTIR spectroscopy, two new non‐invasive biomarkers of skin health have been identified with the potential to help optimise future safe treatment strategies.

Dihydroavenanthramide D Enhances Skin Barrier Function through Upregulation of Epidermal Tight Junction Expression.

Skin barrier dysfunction and thin epidermis are hallmarks of sensitive skin and contribute to premature aging. Avenanthramides are the primary bioactive components of colloidal oatmeal, a commonly used treatment to enhance skin barrier function. This study investigated the relationship between skin barrier function and epidermal characteristics and explored the potential of dihydroavenanthramide D (dhAvD), a synthetic avenanthramide, to improve the skin barrier. We observed a significant correlation between impaired skin barrier function and decreased epidermal thickness, suggesting that a weakened barrier contributes to increased sensitivity. Our in vitro results in HaCaT cells demonstrated that dhAvD enhances keratinocyte proliferation, migration, and tight junction protein expression, thereby strengthening the skin barrier. To mimic skin barrier dysfunction, we treated keratinocytes and full-thickness skin equivalents with IL-4 and IL-13, cytokines that are implicated in atopic dermatitis, and confirmed the downregulation of tight junction and differentiation markers. Furthermore, dhAvD treatment restored the barrier function and normalized the expression of key epidermal components, such as tight junction proteins and natural moisturizing factors, in keratinocytes treated with inflammatory cytokines. In the reconstructed human skin model, dhAvD promoted both epidermal and dermal restoration. These findings suggest that dhAvD has the potential to alleviate skin sensitivity and improve skin barrier function.

Cosmetic retinoid use in photoaged skin: A review of the compounds, their use and mechanisms of action.

The inevitable attrition of skin due to ultraviolet radiation, termed photoaging, can be partially restored by treatment with retinoid compounds. Photoaged skin in lightly pigmented individuals, clinically presents with the appearance of wrinkles, increased laxity, and hyper- and hypopigmentation. Underlying these visible signs of ageing are histological features such as epidermal thinning, dermal-epidermal junction flattening, solar elastosis and loss of the dermal fibrillin microfibrillar network, fibrillar collagen and glycosaminoglycans. Retinoid compounds are comprised of three main generations with the first generation (all-trans retinoic acid, retinol, retinaldehyde and retinyl esters) primarily used for the clinical and cosmetic treatment of photoaging, with varying degrees of efficacy, tolerance and stability. All-trans retinoic acid is considered the 'gold standard' for skin rejuvenation; however, it is a prescription-only product largely confined to clinical use. Therefore, retinoid derivatives are readily incorporated into cosmeceutical formulations. The literature reported in this review suggests that retinol, retinyl esters and retinaldehyde that are used in many cosmeceutical products, are efficacious, safe and well-tolerated. Once in the skin, retinoids utilize a complex signalling pathway that promotes remodelling of photoaged epidermis and dermis and leads to the improvement of the cutaneous signs of photoaging.

Dermoscopic characteristics of Merkel cell carcinoma

BackgroundMerkel cell carcinoma (MCC) is a rare, aggressive, cutaneous tumour with high mortality and frequently delayed diagnosis. Clinically, it often manifests as a rapidly growing erythematous to purple nodule usually located on the lower extremities or face and scalp of elderly patients. There is limited available data on the dermoscopic findings of MCC, and there are no specific features that can be used to definitively diagnose MCC.Aim of the studyHere, we aimed to summarize existing published literature on dermatoscopic and reflectance confocal microscopy (RCM) features of MCC.Materials and methodsTo find relevant studies, we searched the PubMed and Scopus databases from inception to April 12, 2023. Our goal was to identify all pertinent research that had been written in English. The following search strategy was employed: (“ dermoscopy” OR “ dermatoscopy” OR “ videodermoscopy” OR “ videodermatoscopy” OR “ reflectance confocal microscopy”) AND “ Merkel cell carcinoma”. Two dermatologists, DK and GE, evaluated the titles and abstracts separately for eligibility. For inclusion, only works written in English were taken into account.ResultsIn total 16 articles were retrieved (68 cases). The main dermoscopic findings of MCC are a polymorphous vascular pattern including linear irregular, arborizing, glomerular, and dotted vessels on a milky red background, with shiny or non-shiny white areas. Pigmentation was lacking in all cases. The RCM images showed a thin and disarranged epidermis, and small hypo-reflective cells that resembled lymphocytes arranged in solid aggregates outlined by fibrous tissue in the dermis. Additionally, there were larger polymorphic hyper-reflective cells that likely represented highly proliferative cells.ConclusionDermoscopic findings of MCC may play a valuable role in evaluating MCC, aiding in the early detection and differentiation from other skin lesions. Further prospective case-control studies are needed to validate these results.

Ashy Dermatosis: Suatu Laporan Kasus Jarang

Background: Ashy dermatosis is a rare, acquired, benign, and idiopathic hypermelanotic disease. It is manifested asashy-colored lesion with no signs of inflammation. Commonly affected sites of the body include the trunk, neck, face, also proximal and distal extremities. Case: A 33-year-old woman came to Dr. Moewardi Hospital, Surakarta, with chief complaints asymptomatic, ashy colored macule that appear on her right arm. Physical examination in general region shows ashy-colored macule and multiple discrete patches of hyperpigmentation with irregular border. Dermoscopy examinationmacules showed bluish-gray skin markings over bluish background. Histopathological examination showed thin epidermis layer, hyperkeratosis, incontinentia pigmenti, dropping melanin resembles the basal layer civatte bodies. At dermis focal fibrosis was found with infiltrates, incontinentia pigmenti, and dropping melanin. Discussion: Ashy dermatosis or known as erythema dyschromicum perstans is a rare hyperpigmentation disorder that started with reddish, active-bordered lesions, then disappear, leaving a round or oval shape, polycyclic, and ashy macule on the proximal region of the trunk andneck. Onset of symptoms usually at young adult, between first and second decade of life. Etiology of ashy dermatosis is still unclear, and many factors were thought to be involved. Dermoscopy examination showed bluish-gray macules overbluish background. Histopathological examination showed lichenoid reactions and an increase melanin on the dermis. This report aims to describe the diagnosis a rare condition based on anamnesis, physical examination, dermoscopy, and histopathological examination. Clinical findings in this patient were in accordance with the result of previous studies.

O07 Lower doses of retinol facilitate cell proliferation and epidermal thickening in photoaged skin

Abstract Introduction and aims Chronic exposure to solar ultraviolet radiation leads to cutaneous hypertrophic photoageing which clinically manifests as wrinkles, skin laxity and hyperpigmentation. This photoaged phenotype is underscored by a remodelled cutaneous microenvironment including epidermal thinning and rete ridge flattening. We have previously shown that cosmeceutical formulations of 0.3% and 1% retinol can effectively induce epidermal thickening and keratinocyte proliferation. However, these concentrations require careful usage to limit potential irritancy issues, highlighting a need to explore the benefits of lower dose retinol for daily skincare. Therefore, we compare the efficacy of lower doses of retinol in facilitating epidermal thickness and proliferation in photoaged skin, as this currently remains unknown. Methods Using the in vivo Manchester Patch Test Assay, test substances (vehicle and retinol at concentrations of 0.025%, 0.05%, 0.1% and 1%) were applied under occlusion to extensor forearms of healthy but photoaged volunteers (three men, three women; age range 66–86 years) for 12 days. Resultant skin biopsies were processed for histological assessment of epidermal thickness and keratinocyte proliferation. Results Epidermal thickness was significantly increased with 0.025% (P < 0.05), 0.05%, 0.1% and 1% (all P < 0.01) retinol treatment, compared with baseline or vehicle. Immunofluorescence staining of the proliferation marker Ki67 identified elevated keratinocyte proliferation following retinol treatment (P < 0.05 for 0.025%, 0.05% and 1%) compared with baseline. Although Ki67 expression in the 0.1% retinol treatment was elevated, significance was not achieved compared with baseline. However, compared with the vehicle, all retinol concentrations significantly increased Ki67 expression (P < 0.05). Clinically, 50% of volunteers showed an erythemal irritancy response to 1% retinol only. Conclusions We established that lower doses of retinol are capable of inducing keratinocyte proliferation and epidermal thickening without irritancy issues. Therefore, long-term effective treatment of photoaged skin with low-dose retinol products may be the preferred choice for individuals where retinol sensitivity has previously been an issue.

Immunolabeling for filaggrin and acidic keratins in the granular layer of mammalian epidermis indicates that an acidic-basic interaction is involved in cornification

The soft epidermis of mammals derives from the accumulation of keratohyaline granules in the granular layer, before maturing into corneocytes. Main proteins accumulated in the granular layer are pro-filaggrin and filaggrin that determine keratin clumping and later moisturization of the stratum corneum that remains flexible. This soft epidermis allows the high sensitivity of mammalian skin. Presence and thickness of the stratum granulosum varies among different species of mammals and even between different body regions of the same animal, from discontinuous to multilayered. These variations are evident using antibodies for filaggrin, a large protein that share common epitopes among placentals. Here we have utilized filaggrin antibodies (8959 and 466) and an acidic keratin antibody (AK2) for labeling placental, marsupial and monotreme epidermis. AK2 labeling appears mainly to detect K24 keratin, and less likely other acidic keratins. Immunoreactivity for filaggrin is absent in platypus, discontinuous in Echidna and in the tested marsupials. In placentals, it is inconstantly or hardly detected in the thin epidermis of bat, rodents, and lagomorphs with a narrow, mono-stratified and/or discontinuous granular layer. In contrast, where the granular layer is continuous or even stratified, both filaggrin and AK2 antibodies decorate granular cells. The ultrastructural analysis using the AK2 antibody on human epidermis reveals that a weak labeling is associated with keratohyalin granules and filamentous keratins of transitional keratinocytes and corneocytes. This observation suggests that basophilic filaggrin interacts with acidic keratins like K24 and determines keratin condensation into corneocytes of the stratum corneum.

Identification of dihydromyricetin as a natural DNA methylation inhibitor with rejuvenating activity in human skin.

Changes in DNA methylation patterning have been reported to be a key hallmark of aged human skin. The altered DNA methylation patterns are correlated with deregulated gene expression and impaired tissue functionality, leading to the well-known skin aging phenotype. Searching for small molecules, which correct the aged methylation pattern therefore represents a novel and attractive strategy for the identification of anti-aging compounds. DNMT1 maintains epigenetic information by copying methylation patterns from the parental (methylated) strand to the newly synthesized strand after DNA replication. We hypothesized that a modest inhibition of this process promotes the restoration of the ground-state epigenetic pattern, thereby inducing rejuvenating effects. In this study, we screened a library of 1800 natural substances and 640 FDA-approved drugs and identified the well-known antioxidant and anti-inflammatory molecule dihydromyricetin (DHM) as an inhibitor of the DNA methyltransferase DNMT1. DHM is the active ingredient of several plants with medicinal use and showed robust inhibition of DNMT1 in biochemical assays. We also analyzed the effect of DHM in cultivated keratinocytes by array-based methylation profiling and observed a moderate, but significant global hypomethylation effect upon treatment. To further characterize DHM-induced methylation changes, we used published DNA methylation clocks and newly established age predictors to demonstrate that the DHM-induced methylation change is associated with a reduction in the biological age of the cells. Further studies also revealed re-activation of age-dependently hypermethylated and silenced genes in vivo and a reduction in age-dependent epidermal thinning in a 3-dimensional skin model. Our findings thus establish DHM as an epigenetic inhibitor with rejuvenating effects for aged human skin.

Influence of temperature on ‘Rojo Brillante’ persimmon drying. Quality characteristics and drying kinetics

A physico-chemical characterization and drying kinetics study was performed for whole ‘Rojo Brillante’ persimmon subjected to hot-air drying at 35 ᵒC, 40 ᵒC and 45 ᵒC. Fruit was dried until a moisture content of 30 g water/100 g product, which is required to be considered dried persimmon. This moisture value was obtained after 12, 8 and 7 d when the drying process was applied at 35 ᵒC, 40 ᵒC and 45 ᵒC, respectively. All the drying treatments caused flesh structure changes, shrinkage and secondary epidermis formation. The final product's quality characteristics especially the texture, strongly depended on drying temperature. The fruit dried at 35 ᵒC exhibited a gelatinous internal texture and a thin secondary epidermis, similarly to that obtained during a natural drying process. The drying treatment at 40 ᵒC resulted in fruit having more rubbery flesh. However, the fruit dried at 45 ᵒC had a corky texture, with a very thick secondary epidermis that resulted in excessively tough fruit for commercialization purposes. The differences in flesh structure were revealed in the microstructural study by Cryo-FESEM. In all cases, soluble tannins content lowered to non-astringency values. Hot-air drying technology proved to be a good alternative to valorize discarded ‘Rojo Brillante’ persimmon.

Effects of Liquid and Bar Soaps on the Skin of Brazilian Newborns: A Randomized Controlled Trial

Introduction: Compared to adults, newborns’ skin has a thinner epidermis and stratum corneum with decreased hydration levels, higher transepidermal water loss, and a pH variation between 5.5 and 7.5. These characteristics can predispose to the occurrence of dryness, infections, and dermatological conditions. Water and liquid soap with adequate formulation have shown to be beneficial and safe for newborns’ skin. However, studies evaluating the effect of bar soap, products widely used in Brazil and Latin America, are unknown. Therefore, the objective of this study was to compare the effects of liquid and bar soaps on the term newborns’ skin. Methods: This randomized controlled, parallel, single-blind clinical trial was conducted at a public university hospital in São Paulo, Brazil. 100 healthy term newborns with no congenital anomalies, acute diseases, or dermatological conditions were randomized to use liquid soap (experimental group) or bar soap (control group). Skin pH, transepidermal water loss, stratum corneum hydration, sebum content, and skin condition were assessed before and after the first bath, at 48 h, 14 days, and 28 days after birth. These evaluations were performed on the forearm, abdomen, buttocks, and thigh. In addition, the mother’s perception of soap use was also evaluated. Results: Data of 100 newborns were analyzed by intention to treat. The rate of retention was 53%. Newborns exposed to the liquid soap presented significantly better skin acidification (p < 0.001) and significantly better stratum corneum hydration (p < 0.001) than the skin of newborns exposed to the bar soap, regardless of the area evaluated. There were no significant differences in transepidermal water loss, sebum content, dryness, erythema, or skin breakdown and the mother’s perceptions of the use of the soaps. Conclusion: Newborns in the experimental group presented better skin acidification and stratum corneum hydration when compared to newborns in the control group.

A Platform for Testing the Biocompatibility of Implants: Silicone Induces a Proinflammatory Response in a 3D Skin Equivalent.

Biocompatibility testing of materials is carried out in 2D cell cultures or animal models despite serious limitations. 3D skin equivalents are advanced in vitro models for human skin. Silicone has been shown to be noncytotoxic but capable of eliciting an immune response. Our aim was to (1) establish a 3D skin equivalent to (2) assess the proinflammatory properties of silicone. We developed a coculture of keratinocytes and fibroblasts resulting in a 3D skin equivalent with an implant using samples from a breast implant. Samples with and without the silicone implant were studied histologically and immunohistochemically in comparison to native human skin samples. Cytotoxicity was assessed via LDH-assay, and cytokine response was assessed via ELISA. Histologically, our 3D skin equivalents had a four-layered epidermal and a dermal component. The presence of tight junctions was demonstrated in immunofluorescence. The only difference in 3D skin equivalents with implants was an epidermal thinning. Implanting the silicone samples did not cause more cell death, however, an inflammatory cytokine response was triggered. We were able to establish an organotypical 3D skin equivalent with an implant, which can be utilised for studies on biocompatibility of materials. This first integration of silicone into a 3D skin equivalent confirmed previous findings on silicone being non-cell-toxic but capable of exerting a proinflammatory effect.

Immediate diagnosis of cutaneous metastases with optical coherence tomography, line‐field confocal optical coherence tomography and dermoscopy: A case series

AbstractBackgroundCutaneous metastases (CM) are a frequent finding in the follow‐up of malignant tumours.ObjectivesCM were examined with dermoscopy, optical coherence tomography (OCT), dynamic OCT and line‐field confocal OCT (LC‐OCT) to describe common findings.MethodsIn the University Hospital Carl Gustav Carus Dresden, Germany, 18 patients with 61 CM were examined with dermoscopy. CM (n = 43, 31 melanoma metastases, two metastases of renal carcinoma, five metastases of cutaneous squamous cell carcinoma and five metastases of pleomorphic dermal sarcoma) were examined with OCT (VivoSight® Michelson Diagnostics). Additional 18 melanoma metastases were examined with LC‐OCT (deepLive™; Damae Medical).ResultsCM were localized on the head, trunk, neck and limbs. Dermoscopy patterns were angioma‐like, nevus‐like nonglobular, nevus‐like globular, blue nevus‐like and unspecific. CM showed an ulceration, hyperkeratosis with increased entrance signal and disturbed architecture of the epidermis in OCT. In deeper metastases, the dermoepidermal junction (DEJ) was normal; in most cases it was disturbed. CM were visible as subepidermal hyporeflective roundish area, with septae, with either clear margin and shadowing or blurred margin. DOCT showed dot, coiled, serpiginous and branched vessels; there was a disarray in size and distribution and vessels were converging on the centre of the metastasis. In LC‐OCT, CM showed enhanced entrance signal and disturbed architecture of a thinned epidermis, ulceration, atypical honeycomb or cobblestone pattern as well as a broken DEJ. In the dermis, a hyporeflective roundish area with clusters of hyporeflective cells with septae, clear margin and clefting or blurred margin was visible; the hyporeflective area was surrounded by bundles of connective tissue. Subepidermal vessels differentiated in size and distribution. Inflammatory, dendritic and pagetoid cells were visible.ConclusionsOCT and LC‐OCT may be useful tools for immediate diagnosis, localization of CM and monitoring under treatment in addition to conventional methods like ultrasound and histopathology.

Morphoanatomical leaf traits of herbaceous species raised in a cronosequence of naturally regenerated areas of tropical deciduous forest

ABSTRACT Plant survival in semi-arid climates depends on morphological, anatomical, and physiological adjustments that determine survival under limiting environmental conditions. In this study, anatomical and morphological characteristics of three herbaceous species with different growth habits were determined: a tall herb, Mesosphaerum suaveolens (tall), Stachytarpheta sanguinea (short), and Jacquemontia evolvuloides (climbing). Fully expanded leaves were collected from three sites in each of three different natural regeneration periods in a seasonally dry tropical forest. Leaf, specific leaf area, epidermis, cuticle, parenchyma, and mesophyll thicknesses; stomatal and trichome densities were measured. All three species have stomata and trichomes on both leaf surfaces and higher densities on the abaxial surface than the adaxial surface. M. suaveolens and S. sanguinea have unusual leaf morphological and anatomical adjustments, with a larger leaf area in the more open and youngest site, but thicker abaxial and adaxial epidermis and mesophyll in the oldest site which has the closest canopy stratum. J. evolvuloides has more usual adjustments, with a smaller specific leaf area and thinner epidermis and isobilateral parenchyma in the youngest site, being better acclimatized to low water availability and high light incidence. Therefore, M. suaveolens and S. sanguinea have unique acclimatization strategies for different environmental conditions.

Pimecrolimus 1% cream for mild-to-moderate atopic dermatitis: a systematic review and meta-analysis with a focus on children and sensitive skin areas.

This systematic literature review (SLR) and meta-analysis assessed the efficacy and safety of pimecrolimus vs other topical treatments in patients with mild-to-moderate atopic dermatitis (AD), focusing on children and sensitive skin areas. An SLR was conducted in MEDLINE, Embase and Cochrane Library databases on January 15th, 2020, to identify randomized controlled trials (RCTs) with pimecrolimus as a study arm. Another SLR performed on October 5th, 2020 identified RCTs with a crisaborole study arm. Direct pair-wise meta-analysis was used to compare pimecrolimus with vehicle, tacrolimus or topical corticosteroids (TCS; n = 27 studies). Outcomes included Investigator's Global Assessment (IGA) score 0/1 up to week 6 and adverse events. Pimecrolimus was more efficacious than vehicle in achieving IGA 0/1 up to week 6 in children, and similar safety profiles were observed with pimecrolimus and vehicle in children and the mixed population, including on sensitive skin. No significant differences in efficacy and safety were observed between pimecrolimus and tacrolimus 0.03%. Efficacy and safety were similar for pimecrolimus and mild medium potency TCS; mildly potent steroids caused transient epidermal thinning in sensitive skin areas (not seen with pimecrolimus). Pimecrolimus can be considered as a first-line option for mild-to-moderate AD, particularly in children and sensitive skin areas.

Clostridium botulinum C3bot mediated effects on cytokine-induced psoriasis-like phenotype in full-thickness skin model

Clostridium botulinum C3 exoenzyme (C3bot) exclusively inhibits RhoA, B and C by ADP-ribosylation and is therefore used as a cell-permeable tool for investigating the cellular role of these Rho-GTPases. Rho-GTPases represent a molecular switch integrating different receptor signalling to downstream cascades including transcriptional cascades that regulate various cellular processes, such as regulation of actin cytoskeleton and cell proliferation. C3bot-induced inhibition of RhoA leads to reorganization of the actin cytoskeleton, morphological changes, and inhibition of cell proliferation as well as modulation of inflammatory response. In this study, we characterized the C3bot-mediated effects on a full-thickness skin model exhibiting a psoriasis-like phenotype through the addition of cytokines. Indeed, after the addition of cytokines, a decrease in epidermal thickness, parakeratosis, and induction of IL-6 was detected. In the next step, it was studied whether C3bot caused a reduction in the cytokine-induced psoriasis-like phenotypes. Basal addition of C3bot after cytokine induction of the full-thickness skin models caused less epidermal thinning and reduced IL-6 abundance. Simultaneous basal incubation with cytokines and C3bot, IL-6 abundance was inhibited, but epidermal thickness was only moderately affected. When C3bot was added apically to the skin model, IL-6 abundance was reduced, but no further effects on the psoriasis-like phenotype of the epidermis were observed. In summary, C3bot inhibits the cytokine-induced expression of IL-6 and thus may have an impact on the pro-inflammatory immune response in the psoriasis-like phenotype.

Naturally occurring variability in larval period length is associated with intraspecific differences in late tadpoles of a South American true toad

AbstractThe larval period in anurans is highly plastic. Even though larval period length and larval size have been the most studied characteristics showing intraspecific variability, other features such as morphology, behavior, food preferences and physiology have also been described as plastic. Metamorphic changes are triggered by thyroid and interrenal hormones, and environmental signals modulate the onset of metamorphosis via the hypothalamic–pituitary–interrenal axis. The South American bufonid toad Rhinella arenarum from nearby Buenos Aires City has a larval period of 30–120 days under the same environmental conditions. The goal of this study was to evaluate life‐history traits in tadpoles from different localities and potential morphological differences among tadpoles with different larval period length. For this purpose, we reared under natural conditions tadpoles from two different localities nearby Buenos Aires City and in three different years measured their size at the end of metamorphosis and recorded their larval period length. The external appearance, histo‐morphology and morphometry of the skin and kidney/interrenal complex were studied in metamorphs with short and long larval periods (SLP and LLP, respectively). We observed a larval period lasting 30–120 days in tadpoles from different localities or years. SLP metamorphs were smaller, darker, had less protruding eyes without eyelids, a thinner epidermis and fewer skin glands than LLP metamorphs. The secretion of skin glands from SLP tadpoles had acidic glycoconjugates. Kidney size was similar between LLP and SLP metamorphs, but the former had an adult‐like histomorphology. Interrenal gland in LLP early and late climax tadpoles had cells with a high nucleus/cell diameter ratio, a sign of highly active steroidogenic cells. Overall, these results show that intraspecific variability in size, skin and interrenal gland development is associated with differences in larval period length. Distinct skin gland number and secretion, along with distinct interrenal histology at late climax, could have physiological consequences in the post‐metamorphic life.

The Effect of Platelet Rich Plasma versus MSCs Derived Exosomes on the Healing of Burn Injury in Albino Rat: Histological Study

Abstract Background The clinical treatment of skin loss due to severe and massive burns or wounds continues to be a major problem in surgical procedures. Although different kinds of dressings and therapies have been developed, but most of them are expensive. Therefore, new strategies are needed to promote and help in wound healing and repair. Recent studies have demonstrated that exosomes help tissue repair because of high stability, non immune rejection and easy control of dosage and concentration. Platelet-rich plasma (PRP) is an autologous concentration of platelets in concentrated plasma. It has been used to promote soft and hard tissue healing. Aim to compare the effect of MSCs derived exosomes versus PRP on the promotion of healing of experimentally induced second degree partial thickness burn injury in adult male albino rats. Methods The thirty-two adult male albino rats were divided randomly into 4 groups. Group I (control). Group II (burn injury group) that will be left for spontaneous healing. Group III (burn injury treated with PRP intradermal injection). Group IV (burn injury treated with intradermal MSCs derived exosome). All the animals were sacrificed at 7th day (subgroup a) and 21th day (subgroup b). The skin biopsies will be taken and processed for light microscope examination. Results H&amp;E stained section of untreated burn (subgroup IIa) showed coagulative necrosis in epidermis and papillary layer of the dermis. Sign of epithelial migration from the edge of the wound appeared. In Subgroup IIb the surface of the wound was covered by an eschar that converted partial thickness into complete thickness. This resulted in formation of granulation tissue in the dermis. In Subgroup IIIa showed the formation of thin layer of epidermis containing undifferentiated keratinocytes. The underlying dermis contained collagen fibers and beginning of new hair follicles formation. Some specimens in Subgroup IIIb revealed thin epidermis with incomplete differentiation of keratinocytes. Numerous hair follicles were detected in the dermis. However some specimens showed thickened epidermis with presence of rete ridges. The dermis showed few irregularly distributed collagen fibers in granulation tissue with absence of skin appendages. In exosome treated group (subgroup IVa) showed thin epidermis with well differentiated keratinocytes. The dermis contained collagen fibers with absence of skin appendages. Subgroup IVb was more or less similar to the control group. Conclusion The current study revealed that burn treated exosomes group was better than PRP treated group. In addition PRP treated group revealed hyperplastic changes in epidermis with delay in remodeling phase of burn healing.

Identification of an ADAMTS2 frameshift variant in a cat family with Ehlers-Danlos syndrome.

We investigated 4 European domestic shorthair kittens with skin lesions consistent with the dermatosparaxis type of the Ehlers-Danlos syndrome, a connective tissue disorder. The kittens were sired by the same tomcat but were born by 3 different mothers. The kittens had easily torn skin resulting in nonhealing skin wounds. Both clinically and histologically, the skin showed thin epidermis in addition to inflammatory changes. Changes in collagen fibers were visible in electron micrographs. The complete genome of an affected kitten was sequenced. A one base pair duplication leading to a frameshift in the candidate gene ADAMTS2 was identified, p.(Ser235fs*3). All 4 affected cats carried the frameshift duplication in a homozygous state. Genotypes at this variant showed perfect cosegregation with the autosomal recessive Ehlers-Danlos syndrome phenotype in the available family. The mutant allele did not occur in 48 unrelated control cats. ADAMTS2 loss-of-function variants cause autosomal recessive forms of Ehlers-Danlos syndrome in humans, mice, dogs, cattle, and sheep. The available evidence from our investigation together with the functional knowledge on ADAMTS2 in other species allows to classify the identified ADAMTS2 variant as pathogenic and most likely causative variant for the observed Ehlers-Danlos syndrome.