Role Of Skin Research Articles

Using Digital Image Correlation to Quantify Skin Deformation With Von Frey Monofilaments.

Thin von Frey monofilaments are a clinical tool used worldwide to assess touch deficits. One's ability to perceive touch with low-force monofilaments (0.008 - 0.07 g) establishes an absolute threshold and thereby the extent of impairment. While individual monofilaments bend at defined forces, there are no empirical measurements of the skin surface's response. In this work, we measure skin surface deformation at light-touch perceptual limits, by adopting an imaging approach using 3D digital image correlation (DIC). Generating point cloud data from three cameras surveilling the index finger pad, we reassemble and stitch together multiple 3D surfaces. Then, in response to each monofilament's indentation over time, we quantify strain across the skin surface, radial deformation emanating from the contact point, penetration depth into the surface, and area between 2D cross-sections. The results show that the monofilaments create distinct states of skin deformation, which align closely with just noticeable percepts at absolute detection and discrimination thresholds, even amidst variance between individuals and trials. In particular, the resolution of the DIC imaging approach captures sufficient differences in skin deformation at threshold, offering promise in understanding the skin's role in perception.

A role for FcγRIIB in the development of murine bleomycin-induced fibrosis

BackgroundSystemic sclerosis (SSc) is a systemic autoimmune disease characterized by excessive fibrosis. FcγRIIB is a low-affinity receptor for the Fc fragment of IgG. FcγRIIB is expressed on the surface of various leukocyte subsets and signals negative feedback pathways to down-regulate B-cell antigen receptor signaling. ObjectiveThe aim of the present study was to investigate the role of FcγRIIB in the development of a murine bleomycin-induced scleroderma model. MethodsThe experimental fibrosis model was generated by the intradermal injection of bleomycin into wild-type (WT) and FcγRIIB-deficient (FcγRIIB-/-) mice. We histologically assessed skin and lung fibrosis as well as inflammatory cell infiltration. Cytokine and chemokine expression levels were measured with RT-PCR. ResultsThe severity of fibrosis in the skin and lung was significantly worse in FcγRIIB-/- mice than in WT mice. In the skin of bleomycin-treated mice, the numbers of CD8+ T cells, F4/80+ macrophages, MPO+ neutrophils, NK1.1+NK cells, and B220+ B cells were significantly higher in FcγRIIB-/- mice than in WT mice. The expression of TNF-α and IL-1β was significantly higher in FcγRIIB-/- mice than in WT mice as was the expression of ICAM-1, CXCL2, and CCL3 in the affected skin. An adoptive transfer of splenic leukocytes from FcγRIIB-/- mice into WT mice showed exacerbated skin and lung fibrosis compared to WT mice without an adoptive transfer. ConclusionThese results indicate that FcγRIIB plays an inhibitory role in skin and lung fibrosis. Moreover, modulating FcγRIIB signaling has potential as a therapeutic approach for SSc.

Circ_NCKAP1 promotes skin basal cell carcinoma progression by sponging the miR-148b-5p/HSP90 axis.

Skin basal cell carcinoma (BCC) is the most common malignant skin tumor. Recent studies demonstrated that circular RNAs (circRNAs) are implicated in tumorigenesis and may represent potential therapeutic targets. The aim of the present study was to explore the expression profiles of circRNAs and their role in skin BCC. Three pairs of skin BCC tissues and adjacent tissues were used to perform a circRNA microarray for screening of circRNA expression profiles. Circ_NCKAP1 was selected as a target circRNA by RT-qPCR verification and bioinformatics analysis. The effect of circ_NCKAP1 knockdown on cell proliferation and apoptosis was assessed using CCK8 and Annexin V-FITC/PI assays, and its regulation over the miR-148b-5p/HSP90 axis was assessed by dual-luciferase reporter assay. Circ_NCKAP1 was found to be significantly upregulated in skin BCC tissues (p<0.05). In vitro loss-of-function assays demonstrated that circ_NCKAP1 knockdown markedly inhibited cell proliferation and promoted cell apoptosis (p<0.05). Moreover, Dual-Luciferase reporter assay identified that circ_NCKAP1 could bind to miR-148b-5p directly, and HSP90 was targeted by miR-148b-5p. Circ_NCKAP1 can promote skin BCC progression by sponging the miR-148b-5p/HSP90 axis, and circ_NCKAP1 may be a potential target for skin BCC therapy.

LB811 Exosomes from human neonatal fibroblasts conditioned media play an important role in skin rejuvenation

Extracellular vesicles (EVs), including exosomes, are lipid bilayer delimited particles that are naturally released from a cell and play a major role in the communication of various cells by serving as vehicles to transfer cytosolic proteins, lipids, and RNAs between cells. Cell culture conditioned media (CCM) from human neonatal fibroblasts cultured under hypoxic conditions have demonstrated potential to stimulate wound healing and skin regeneration. EVs are known to secrete into medium from cultured cells; therefore we characterized the content of exosomes from CCM to investigate its potential role in skin.

Modulation of macrophage functions by ECM-inspired wound dressings- a promising therapeutic approach for chronic wounds.

Nonhealing chronic wounds are among the most common skin disorders with increasing incidence worldwide. However, their treatment is still dissatisfying, that is why novel therapeutic concepts targeting the sustained inflammatory process have emerged. Increasing understanding of chronic wound pathologies has put macrophages in the spotlight of such approaches. Herein, we review current concepts and perspectives of therapeutic macrophage control by ECM-inspired wound dressing materials. We provide an overview of the current understanding of macrophage diversity with particular view on their roles in skin and in physiological and disturbed wound healing processes. Based on this we discuss strategies for their modulation in chronic wounds and how such strategies can be tailored in ECM-inspired wound dressing. The latter utilize and mimic general principles of ECM-mediated cell control, such as binding and delivery of signaling molecules and direct signaling to cells specifically adapted for macrophage regulation in wounds. Inthis review, we present examples of most recent approaches and discuss ideas for their further development.

PH and Proton Sensor GPR65 Determine Susceptibility to Atopic Dermatitis.

pH sensing by GPR65 regulates various inflammatory conditions, but its role in skin remains unknown. In this study, we performed a phenome-wide association study and report that the T allele of GPR65-intronic single-nucleotide polymorphism rs8005161, which reduces GPR65 signaling, showed a significant association with atopic dermatitis, in addition to inflammatory bowel diseases and asthma, as previously reported. Consistent with this genetic association in humans, we show that deficiency of GPR65 in mice resulted in markedly exacerbated disease in the MC903 experimental model of atopic dermatitis. Deficiency of GPR65 also increased neutrophil migration in vitro. Moreover, GPR65 deficiency in mice resulted in higher expression of the inflammatory cytokine TNF-α by T cells. In humans, CD4+ T cells from rs8005161 heterozygous individuals expressed higher levels of TNF-α after PMA/ionomycin stimulation, particularly under pH 6 conditions. pH sensing by GPR65 appears to be important for regulating the pathogenesis of atopic dermatitis.

TRPV1: Role in Skin and Skin Diseases and Potential Target for Improving Wound Healing.

Skin is innervated by a multitude of sensory nerves that are important to the function of this barrier tissue in homeostasis and injury. The role of innervation and neuromediators has been previously reviewed so here we focus on the role of the transient receptor potential cation channel, subfamily V member 1 (TRPV1) in wound healing, with the intent of targeting it in treatment of non-healing wounds. TRPV1 structure and function as well as the outcomes of TRPV1-targeted therapies utilized in several diseases and tissues are summarized. In skin, keratinocytes, sebocytes, nociceptors, and several immune cells express TRPV1, making it an attractive focus area for treating wounds. Many intrinsic and extrinsic factors confound the function and targeting of TRPV1 and may lead to adverse or off-target effects. Therefore, a better understanding of what is known about the role of TRPV1 in skin and wound healing will inform future therapies to treat impaired and chronic wounds to improve healing.

Out of the shadow of interleukin-17A: the role of interleukin-17F and other interleukin-17 family cytokines in spondyloarthritis.

Purpose of reviewThe last decade has witnessed tremendous advances in revealing an important role for the interleukin (IL)-17 cytokine family in the pathogenesis of spondyloarthritis (SpA). Although most attention has been focused on IL-17A, a potential role of other IL-17 family members in inflammation and tissue remodelling is emerging. Herein, I review recent studies covering the role of IL-17B-F cytokines in the pathogenesis of SpA.Recent findingsSeveral recent studies provided new insights into the cellular source, regulation and function of IL-17F. IL-17F/IL-17A expression ratio is higher in psoriatic skin compared to SpA synovitis. IL-17F-expressing T cells produce different proinflammatory mediators than IL-17A-expressing cells, and IL-17F and IL-17A signal through different receptor complex. Dual IL-17A and IL-17F neutralization resulted in greater suppression of downstream inflammatory and tissue remodelling responses. Furthermore, there is additional evidence of IL-23-independent IL-17 production. In contrast to IL-17A, IL-17F and IL-17C, which play proinflammatory roles in skin and joint inflammation, an anti-inflammatory function is proposed for IL-17D. An increase in IL-17E is associated with subclinical gut microbiome alterations after anti-IL-17A therapy in SpA patients.SummaryIL-17 family cytokines may act as agonists or antagonists to IL-17A contributing in concert to local inflammatory responses. Understanding their function and identifying their cellular sources, and molecular mechanisms driving their expression will be the key to designing rational therapies in SpA.

Destruction, Reconstruction and Resistance: The Skin and the Protean Body in Pedro Almodóvar’s Body Horror The Skin I Live In

The instinct to tame and preserve and the longing for eternal beauty makes skin a crucial element in the genre of the Body Horror. By applying a gendered reading to the art of destruction and reconstruction of an ephemeral body, this paper explores the significant role of skin that clothes a protean body in Almodóvar’s unconventional Body Horror, “The Skin I Live In” (2011). Helpless vulnerable female bodies stretched on beds and close shots of naked perfect skin of those bodies are a frequent feature in Almodóvar films. Skin stained and blotched in “Tie Me Up! Tie Me Down!” (1989), nurtured and replenished in “Talk to Her” (2002), patched up and stitched in “The Skin I Live In”, becomes a key ingredient in Almodóvar’s films that celebrate the fluidity of human anatomy and sexuality. The article situates “The Skin I Live In” in the filmic continuum of Body Horrors that focus primarily on skin, beginning with Alfred Hitchcock’s “Psycho” (1960), and touching on films like Jonathan Demme’s “The Silence of the Lambs” (1991) and Tom Tykwer’s “Perfume: The Story of a Murderer” (2006) and attempts to understand how the exploited bodies that have been culturally and socially subjugated have shaped the course of the history of Body Horrors in cinema. In “The Skin I Live In” the destruction of Vicente’s body and its recreation into Vera follow a mad scientist’s urge to dominate an unattainable body, but this ghastly assault on the body has the onscreen appearance of a routine surgical operation by an expert cosmetologist in a well-lit, sanitized mise-en-scène, suggesting that the uncanny does not need a dungeon to lurk in. The exploited body on the other hand may be seen not as a passive victim, but as a site of alterity and rebellion. Anatomically a complete opposite of Frankenstein’s Creature, Vicente/Vera’s body, perfect, beautiful but beset with a problematized identity, is etched with the history of conversion, suppression, and the eternal quest for an ephemeral object. Yet it also acts as an active site of resistance.

The Potential of Nail Mini-Organ Stem Cells in Skin, Nail and Digit Tips Regeneration.

Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the nail plate. Furthermore, the slow-cycling population of the nail proximal fold (nail proximal fold stem cells (NPFSCs)) displays bifunctional properties by contributing to the peri-nail epidermis under the normal homeostasis and the nail structure upon injury. Here, we discuss nail mini-organ stem cells’ location and their role in skin and nail homeostasis and regeneration, emphasizing their importance to orchestrate the whole digit tip regeneration. Such endogenous regeneration capabilities are observed in rodents and primates. However, they are limited to the region adjacent to the nail’s proximal area, indicating the crucial role of nail mini-organ stem cells in digit restoration. Further, we explore the molecular characteristics of nail mini-organ stem cells and the critical role of the bone morphogenetic protein (BMP) and Wnt signaling pathways in homeostatic nail growth and digit restoration. Finally, we investigate the latest accomplishments in stimulating regenerative responses in regeneration-incompetent injuries. These pioneer results might open up new opportunities to overcome amputated mammalian digits and limbs’ regenerative failures in the future.

Orange corn diets associated with lower severity of footpad dermatitis in broilers

Footpad dermatitis (FPD), damage and inflammation of the plantar surface of the foot, is of concern for poultry because FPD affects the birds' welfare and production value. Footpad dermatitis is painful and causes costly chicken paw downgrades, carcass condemnations, and reduced live weights. However, a universal preventative has not been found. The hypothesis was that diets containing orange corn, when compared with diets containing yellow or white corn, would reduce the severity of footpad dermatitis in broiler chickens on wet litter. When compared with yellow and white corn, orange corn contains higher quantities of carotenoids, antioxidant pigments, believed to play a role in skin and feather health. This experiment was a randomized block, 3 × 2 factorial design: orange, yellow, and white corn diets with birds raised on wet or dry litter (control group). Female Ross 708 broilers (n = 960) were used to create 4 replicates of each diet x litter treatment combination. Footpads were scored at day 19, 27, 35, and 42, following the Global Animal Partnership standard's 0–2 scale of visual increasing severity: 0 indicates minimal damage and 1 and 2 indicate mild to severe lesions and ulceration, dark papillae, and/or bumble foot. At 42 d of age, birds on the wet litter had greater severity of FPD, scores 1 and 2, compared with the control group (88 vs. 13% respectively; P < 0.0001). At 42 d of age, prevalence of more severe footpad scores, 1 or 2, was lowest on the orange corn diet (33%), followed by white corn (56%) and yellow corn (63%). Birds fed the orange corn diet had higher BW throughout the study (P = 0.004) and had fat pads and livers with higher yellow pigment deposition (P < 0.005). Litter moisture content altered microbiome composition but corn type did not. In conclusion, the main determinant of FPD in this study was exposure to wet litter. When compared with yellow and white corn, orange corn was associated with improved bird growth and reduced severity of footpad dermatitis, especially at later time points.

Immunohistochemical Expression of Heparanase-2 in Psoriasis

Background: Psoriasis is a chronic, inflammatory immune mediated skin disease characterized by dense infiltrates of immunocytes especially macrophages. Cross talk between immunocytes and keratinocytes is thought to mediate the disease. Hparanase 2 inhibits activity of Heparanase 1 which is involved in this cross talk by degradation of heparin sulphate chains in the basement membrane and extra cellular matrix (ECM). Objective: To assess the of Heparanase2 in psoriasis through its immunohistochemical expression in lesional and perilesional skin of psoriasis patients. Patients and Methods: This prospective case control study was carried out on a total number of 60 subjects, they included 30 patients with chronic plaque psoriasis and 30 age and gender matched apparently normal subjects as control group. Skin biopsies were taken for immunohistochemical evaluation of Heparanase 2 expression. Results: Our results showed significant difference between lesional, perilesional and control groups regarding the status of epidermal Heparanase 2 expression (P = 0.038). All lesional epidermal expression was negative while perilesional epidermal expression was negative in 24 (80%) cases and positive in 6 (20%) cases, control epidermal expression was negative in 27 (90%) cases and positive in 3 (10%) cases. There was no significant difference between the three studied groups regarding dermal Heparanase 2 expression (P = 0.318). Conclusion: Downregulation of Heparanase 2 could be incriminated in the pathogenesis of psoriasis. Heparanase 2 could have a protective role in skin.

Immunohistochemical Expression of Heparanase-2 in Psoriasis

Background: Psoriasis is a chronic, inflammatory immune mediated skin disease characterized by dense infiltrates of immunocytes especially macrophages. Cross talk between immunocytes and keratinocytes is thought to mediate the disease. Hparanase 2 inhibits activity of Heparanase 1 which is involved in this cross talk by degradation of heparin sulphate chains in the basement membrane and extra cellular matrix (ECM). Objective: To assess the of Heparanase2 in psoriasis through its immunohistochemical expression in lesional and perilesional skin of psoriasis patients. Patients and Methods: This prospective case control study was carried out on a total number of 60 subjects, they included 30 patients with chronic plaque psoriasis and 30 age and gender matched apparently normal subjects as control group. Skin biopsies were taken for immunohistochemical evaluation of Heparanase 2 expression. Results: Our results showed significant difference between lesional, perilesional and control groups regarding the status of epidermal Heparanase 2 expression (P = 0.038). All lesional epidermal expression was negative while perilesional epidermal expression was negative in 24 (80%) cases and positive in 6 (20%) cases, control epidermal expression was negative in 27 (90%) cases and positive in 3 (10%) cases. There was no significant difference between the three studied groups regarding dermal Heparanase 2 expression (P = 0.318). Conclusion: Downregulation of Heparanase 2 could be incriminated in the pathogenesis of psoriasis. Heparanase 2 could have a protective role in skin.

Study On Skin Fold Thickness in Newborns as an Index of Foetal Nutritional Assessment

Introduction: Skin fold thickness is a measure of adiposity and is a validated method of assessing malnutrition in older children. The present study was undertaken to see the role of skin fold thickness measurement in neonates as an index of foetal nutritional assessment and to compare between CAN (Clinical Assessment of Nutrition) score and other anthropometric indicators in foetal malnutrition (FM).&#x0D; Methods: A prospective observational study was conducted in postnatal ward of Universal College of Medical Sciences-Teaching Hospital for a duration of six months. Three hundred seventy term newborns were assessed by CAN score and anthropometry recorded. The CAN score was determined and those with scores &lt; 25 was classified as having foetal malnutrition. Skin fold thickness using the Slim Guide skin fold caliper was taken at the triceps, biceps, sub scapular, supra iliac and quadriceps locations for each neonate. Two readings were taken at every site and the mean was recorded. All the skin fold thickness measurements were correlated with the CAN score and statistical comparisons were made.&#x0D; Results: Incidence of FM was 18.38%. The mean (SD) for sum of all skin-fold thickness at all sites for males and females were 4.3 ± 1.61 and 4.18 ± 0.72 mm respectively. All the skin-fold thickness measurements correlated significantly with the CAN score, but the sum of the five had the best correlation. The mean (SD) of anthropometric data of babies and sum of all comparing foetal malnutrition versus without foetal malnutrition using nutritional status CAN score was statistically significant (p-value &lt; 0.001). &#x0D; Conclusions: The sum of all five skin-fold measurements might be a useful screening tool for FM in view of its objectivity, convenience and simplicity, but it is not sufficiently sensitive or specific to replace the CAN score in the identification of FM in neonates.

16294 Evaluating prebiotic effects of glycerol: Moving toward enhancing the care of infant skin

Background: It is well accepted that infant skin barrier is more vulnerable than adult and that the microbiome plays a critical role in skin’s natural defense. Therefore, it is important to nourish both the barrier and microbiome, to allow for their natural maturation. Glycerol is a humectant proven to hydrate skin. Previous in vitro studies have shown that glycerol can also be utilized by skin commensal bacteria as a food source, making glycerol a “skin prebiotic” ingredient.

Very Long-Chain Branched-Chain Fatty Acids in Chia Seeds: Implications for Human Use.

Dairy and fermented foods are common sources of dietary branched-chain fatty acids (BCFA) of chain lengths C13-C18 serving a putative prebiotic role and a component of human integument. Few studies have reported on nonfermented plant-derived BCFA in human diets or cosmetics. A three-ion monitoring method was adapted to confirm branch position of ultratrace (<0.01%, w/w) BCFA. We identified chia as a new source of BCFA with C15-C35 chain lengths. Surprisingly, even-numbered very long-chain BCFA (VLC BCFA), anteiso-22:0, anteiso-24:0, and anteiso-26:0 were unequivocally identified in natural products for the first time. Plant-derived BCFA are predominantly anteiso, in contrast with similar iso and anteiso levels in ruminant and fermented foods. Chia seeds contain 0.4% BCFA, w/w of total fatty acids, or 32 mg BCFA in a food serving, surpassing other plant oils. Topical administration of chia seed oil containing VLC BCFA may have a role in skin and hair functionality.

In vitro protective effects of Paeonia officinalis var. mascula callus extract on human keratinocytes

Natural ingredients have been used to improve the state of health in humans. The genus Paeonia has been studied only limited yet it’s reported to have many activities such as antioxidant and anti-inflammatory. To this context, here we focused on an endemic Paeonia species in Attica. This study aims to present the development of the Paeonia officinalis var. mascula callus extract and its pleiotropic bioactivity on human primary keratinocytes exploring its potential application as an active agent in skin-related products. This extract showed a high scavenging activity with high phenolic content and an interesting metabolic profile. At a molecular level, the study on the transcript accumulation of genes revealed that this extract exhibits in vitro skin-related protection properties by mediating mitochondrial energy, cell proliferation, immune and inflammatory response and positively regulates genes involved in epidermal and in stratum corneum function. Besides, the extract is proven not skin irritant on reconstructed human skin model. These findings indicate that the specific P. officinalis var. mascula extract possesses significant in vitro protection activity on human epidermis and provides new insights into its beneficial role in skin confirming that the advent of biotechnology contribution the past few decades.

Histidine Metabolism and Function

Histidine is a dietary essential amino acid because it cannot be synthesized in humans. The WHO/FAO requirement for adults for histidine is 10mg · kg body weight-1 · d-1. Histidine is required for synthesis of proteins. It plays particularly important roles in the active site of enzymes, such as serine proteases (e.g., trypsin) where it is a member of the catalytic triad. Excess histidine may be converted to trans-urocanate by histidine ammonia lyase (histidase) in liver and skin. UV light in skin converts the trans form to cis-urocanate which plays an important protective role in skin. Liver is capable of complete catabolism of histidine by a pathway which requires folic acid for the last step, in which glutamate formiminotransferase converts the intermediate N-formiminoglutamate to glutamate, 5,10 methenyl-tetrahydrofolate, and ammonia. Inborn errors have been recognized in all of the catabolic enzymes of histidine. Histidine is required as a precursor of carnosine in human muscle and parts of the brain where carnosine appears to play an important role as a buffer and antioxidant. It is synthesized in the tissue by carnosine synthase from histidine and β-alanine, at the expense of ATP hydrolysis. Histidine can be decarboxylated to histamine by histidine decarboxylase. This reaction occurs in the enterochromaffin-like cells of the stomach, in the mast cells of the immune system, and in various regions of the brain where histamine may serve as a neurotransmitter.

The Role of Skin and Gut Microbiome and Epigenetic Modifications in Skin-Autoimmune Disorders.

Human microbiota and immune system are strictly connected to each other. Several studies demonstrated that normal skin and/or gut floral alterations may have negative consequences on disease pathogenesis. Indeed, a strong association between skin and gut microbiota alterations and autoimmune diseases was found. Moreover, a significant interplay between microbiome and miRNAs expression was noticed among several conditions. The aim of this review article is to shed new light on some of the commonest skin disorders such as psoriasis, atopic dermatitis, allergic contact dermatitis, with special regard to epigenetic pathogenetic mechanisms such as miRNAs expression and skin and gut microbiome alterations. Indeed, evidence is still lacking regarding these two factors and their possible interactions. We believe their implications may be crucial for screening, early diagnosis and also therapeutic strategies; therefore, this field could represent a promising challenge for further studies.

Microfluidic Skin-on-a-Chip Models: Toward Biomimetic Artificial Skin.

The role of skin in the human body is indispensable, serving as a barrier, moderating homeostatic balance, and representing a pronounced endpoint for cosmetics and pharmaceuticals. Despite the extensive achievements of in vitro skin models, they do not recapitulate the complexity of human skin; thus, there remains a dependence on animal models during preclinical drug trials, resulting in expensive drug development with high failure rates. By imparting a fine control over the microenvironment and inducing relevant mechanical cues, skin-on-a-chip (SoC) models have circumvented the limitations of conventional cell studies. Enhanced barrier properties, vascularization, and improved phenotypic differentiation have been achieved by SoC models; however, the successful inclusion of appendages such as hair follicles and sweat glands and pigmentation relevance have yet to be realized. The present Review collates the progress of SoC platforms with a focus on their fabrication and the incorporation of mechanical cues, sensors, and blood vessels.