Dermal Layer Of Skin Research Articles

Methylglyoxal impairs human dermal fibroblast survival and migration by altering RAGE-hTERT mRNA expression in vitro

Fibroblasts are native residents in dermal layer of human skin which are important for dermal regeneration and essential during cutaneous wound healing by releasing inflammatory markers and actively migrate to close an open wound. Premature skin ageing due to methylglyoxal (MGO) has recently caught the attention considering its potential to accelerate the emergence of skin ageing signs, however previous studies were only focused in primary neonatal dermal fibroblast and NIH3t3 fibroblast cell line. Therefore, thorough investigation is required to study the impact of MGO on primary human dermal fibroblast isolated from adult subject (HDFa). In our experiments, short exposure of MGO was observed to induced significant reductions in cell viability at concentrations of 7.5, 10, 12.5, 15, and 17.5 mM (p < 0.005) after 3 hours of treatment. The cellular death of HDFa at 10, 12.5 and 15 mM of MGO were also marked by increased in intracellular ROS level, indicating the involvement of oxidative stress-induced death in these cells. We also observed enlarge scratch areas of cells exposed with 7.5 and 10 mM MGO compared to control after 26 hours, thereby suggesting a decline in cell migration and viability in this group. We propose the increased ROS as the consequence of AGE-RAGE activation which was marked by significant elevation of RAGE mRNA on cells exposed to 10 mM MGO. Our data also suggest the occurrence of DNA damage events via ROS-induced oxidation or mediated by decline in hTERT mRNA expression.

Comparative Study on Enhanced Skin Permeation Efficiency of Phenylephrine via Novel Lipid Vesicles: A Promising Approach in Preventing Chemotherapy-Induced Alopecia Management.

Chemotherapy-induced alopecia (CIA) significantly impacts patients' emotional and psychological well-being and treatment regimen. Phenylephrine, a topical vasoconstrictor, can potentially reduce hair loss by limiting chemotherapy drug delivery to hair follicles. However, effective delivery of Phenylephrine through the skin remains challenging. This study investigates lipid vesicles as delivery vehicles to enhance Phenylephrine's skin permeation and sustained release due to their biocompatibility and encapsulation capabilities. This study aimed to formulate and compare different lipid vesicles of Phenylephrine HCl for enhanced permeation through the skin for deep dermal delivery with sustained release of the drug so as to achieve local vasoconstriction. Phenylephrine-loaded ethosomes, invasomes, and transfersomes were prepared and characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE %). These lipid vesicles were incorporated into hydrogels to facilitate sustained drug release to deep dermal layers where they could target local vasculature and cause vasoconstriction. The prepared vesicular gels were evaluated for various permeation parameters. The entrapment efficiencies of the developed vesicles ranged from 49.51 ± 3.25% to 69.09 ± 2.32%, with vesicle sizes ranging from 162.5 ± 5.21 nm to 321.32 ± 3.75 nm. Statistical analysis revealed significantly higher flux values (Jss, μg/cm2 h) of 0.6251, 0.6314, and 0.4075 for invasomal gel, ethosomal gel, and transfersomal gel, respectively, compared to plain gel (0.1254) (p < 0.005). The enhancement factors were 4.9848, 5.0350, and 3.2496 for invasomal gel, ethosomal gel, and transfersomal gel, respectively, indicating superior permeation abilities of ethosomal and invasomal formulations. The results demonstrate that ethosomal and invasomal formulations were efficient in delivering the drug to deep dermal layers of skin in a sustained manner. These findings suggest that these Lipidic vesicles would be able to target the local vasoconstrictor to vasculature, causing reduced hair loss by limiting chemotherapy drug delivery to hair follicles and managing chemotherapy-induced alopecia.

Cyanocobalamin-loaded dissolving microneedles diminish skin inflammation in vivo

Inflammatory diseases of the skin have a considerable high prevalence worldwide and negatively impact the patients' quality of life. First-line standard therapies for these conditions inherently entail important side effects when used long-term, particularly complicating the management of chronic cases. Therefore, there is a need to develop novel therapeutic strategies to offer reliable alternative treatments. Abnormally high reactive oxygen species (ROS) levels are characteristic of this kind of illnesses, and therefore a reasonable therapeutic goal. Cyanocobalamin, also known as Vitamin B12, possesses notable antioxidant and ROS-scavenging properties which could make it a possible therapeutic alternative. However, its considerable molecular weight restricts passive diffusion through the skin and forces the use of an advanced transdermal delivery system. Here, we present several prototypes of Cyanocobalamin-loaded Dissolving Microarray Patches (B12@DMAPs) with adequate mechanical properties to effectively penetrate the stratum corneum barrier, allowing drug deposition into the skin structure. Ex vivo penetration and permeability studies noted an effective drug presence within the dermal skin layers; in vitro compatibility studies in representative cell skin cell lines such as L929 fibroblasts and HaCaT keratinocytes ensured their safe use. The in vivo efficacy of the selected prototype was tested in a delayed-type hypersensitivity murine model that mimics an inflammatory skin process. Several findings such as a reduction of MPO-related photon emission in a bioluminescence study, protection against histological damage, and decrease of inflammatory cytokines levels point out the effectivity of B12@DMAPs to downregulate the skin inflammatory environment. Overall, B12@DMAPs offer a cost-effective translational alternative for improving patients' skin healthcare.

Does hydrogen peroxide help mitigate the incidence of Cutibacterium acnes in cervical spine surgeries?

Background: Surgical site infection (SSI) is a common yet serious complication of cervical spine surgery. While initially thought to be clinically insignificant, Cutibacterium acnes (C. acnes) is an important cause of infection. The purpose of this study was to investigate the ability of an hydrogen peroxide (H2O2) application during standard pre-surgical skin preparation to reduce the burden of C. acnes in patients undergoing cervical spine surgery. Methods: This was a retrospective review of prospectively collected data. Subjects were randomly assigned to either standard surgical preparation plus H2O2 (experimental) or without H2O2 (control). Pre-scrub, post-scrub, and dermal cultures were obtained to assess the C. acnes burden after cultures on an aerobic and anaerobic growth medium were held for 21 days. Multivariate analysis was conducted to determine factors associated with presence of C. acnes. Outcome measures included the results of intraoperative cultures and the development of a SSI within 90 days post-operatively. Results: Patients (n=86) undergoing elective two- or three-level fusion via anterior approach were included. Prior to application of the antiseptic solution, 65% (28/43) of the experimental cohort and 77% (33/43) of the control cohort had positive C. acnes cultures (p=0.34). Following application of antiseptic solution, there were no differences in positive C. acnes culture rates between the experimental and control cohorts in the epidermal (30% versus 28%, p=1.00) or dermal (40% versus 42%, p=1.00) cultures. No differences in the rates of C. acnes eradication from pre-antiseptic to post-antiseptic application occurred for epidermal (p= 1.00) or dermal (p= 1.00) skin layers. None of the factors were associated with positive C. acnes epidermal cultures on multivariable logistic regression analysis (p> 0.05). Conclusions: While there is potential for H2O2 to reduce the positive culture rate of C. acnes in cervical spine patients, no difference was seen when compared to standard surgical skin preparation.

The Dynamic Relationship between Dengue Virus and the Human Cutaneous Innate Immune Response.

Dengue virus (DENV) is a continuing global threat that puts half of the world's population at risk for infection. This mosquito-transmitted virus is endemic in over 100 countries. When a mosquito takes a bloodmeal, virus is deposited into the epidermal and dermal layers of human skin, infecting a variety of permissive cells, including keratinocytes, Langerhans cells, macrophages, dermal dendritic cells, fibroblasts, and mast cells. In response to infection, the skin deploys an array of defense mechanisms to inhibit viral replication and prevent dissemination. Antimicrobial peptides, pattern recognition receptors, and cytokines induce a signaling cascade to increase transcription and translation of pro-inflammatory and antiviral genes. Paradoxically, this inflammatory environment recruits skin-resident mononuclear cells that become infected and migrate out of the skin, spreading virus throughout the host. The details of the viral-host interactions in the cutaneous microenvironment remain unclear, partly due to the limited body of research focusing on DENV in human skin. This review will summarize the functional role of human skin, the cutaneous innate immune response to DENV, the contribution of the arthropod vector, and the models used to study DENV interactions in the cutaneous environment.

Differentiation of keratinocytes or exposure to type 2 cytokines diminishes S. aureus internalization.

Staphylococcus aureus is a leading cause of skin and soft tissue infections. Colonization by this bacterium is increased in individuals with chronic cutaneous diseases such as atopic dermatitis, psoriasis, and bullous pemphigoid. The greater abundance of S. aureus on the skin of subjects with atopic dermatitis in particular has been linked to recurrent cutaneous infections. The primary cell type of the epidermal layer of the skin is the keratinocyte, and it is thought that S. aureus internalized in keratinocytes associates with an increased incidence of skin infections. This study addresses whether keratinocyte differentiation and/or inflammation, two important characteristics altered in cutaneous diseases, influence bacterial internalization. To do this, S. aureus internalization was measured in immortalized and primary keratinocytes that were differentiated using high Ca2+-containing media and/or exposed to cytokines characteristic of atopic dermatitis (IL-4 and IL-13) or psoriasis (IL-17A and IL-22) skin. Our results indicate that S. aureus internalization is uniquely decreased upon keratinocyte differentiation, since this was not observed with another skin-resident bacterium, S. epidermidis. Additionally, treatment with IL-4 + IL-13 diminished bacterial internalization. We interpret this decrease as a mechanism of keratinocyte-based bacterial killing since a similar number of bacterial genomes were detected in cytokine-treated cells, but less viable internalized S. aureus was recovered. Finally, of the receptors reported for S. aureus binding/internalizing into keratinocytes, expression of the α5 component of the α5β1 integrin was in greatest accordance with the number of internalized bacteria in the context of keratinocyte differentiation.IMPORTANCEIndividuals with chronic cutaneous diseases demonstrate heightened susceptibility for severe and recurrent infections from Staphylococcus aureus. What drives this altered susceptibility remains poorly understood. Previous publications have detected S. aureus as deep as the dermal layer of skin in subjects with atopic dermatitis, suggesting that the cutaneous environment of this disease enables deeper bacterial infiltration than occurs in healthy individuals. This observation indicates that S. aureus has greater opportunity to interact with multiple skin cell types in individuals with chronic inflammatory skin diseases. Identifying the characteristics of the skin that influence bacterial internalization, a common method to establish reservoirs and evade the immune response, is critical for our understanding of S. aureus pathogenesis. The significance of this research is the novel identification of epidermal characteristics that influence S. aureus internalization. With this knowledge, methods can be developed to identify patient populations at greater risk for cutaneous infections.

Characterization of the collagen network of human cheek skin using ultrasonic microscopy

Dermal collagen is the most abundant component of human skin and has a network structure that regulates the mechanical properties of the skin. Therefore, non-invasive characterization of the collagen network would be beneficial for the evaluation of skin conditions. The microscopic substructures of the network, which are individual bundles and fibers, have been optically investigated. However, the macroscopic structure of the collagen network has not been assessed. To evaluate the dermal collagen network, we developed two new indicators, volume filling factor (VFF) and collagen fiber texture (CFT), to analyze three-dimensional echo intensity maps of high-frequency ultrasonic microscopy. By identifying the difference in the elastic modulus components of the dermal layer of facial skin, the density and texture of the collagen network were characterized using VFF and CFT, respectively. These new indicators revealed that the density decreased and the texture became fine with facial age. This study demonstrates that ultrasonic microscopy is useful for investigating skin conditions, paving the way for diagnostic applications in dermatology and aesthetic medicine.

Liposomes and transferosomes in the delivery of papain for the treatment of keloids and hypertrophic scars

Hypertrophic scars and keloids are characterized by an excessive collagen deposition. The available treatment options are invasive and can result in recurrence of scar formation. Using liposomes and transferosomes for the topical delivery of papain, a proteolytic enzyme, can be effective treatment. The objective of the study is to formulate papain-loaded liposomes and transferosomes, characterize the formulations, and study in vitro permeation using shed snake skin and Sprague-Dawley rat skin as models for stratum corneum and full thickness skin. Papain-loaded liposomes and transferosomes were formulated using the thin-film hydration method for the delivery of papain across the stratum corneum barrier. An in vitro permeation study carried out using shed-snake skin and Sprague-Dawley rat skin models showed that transferosomes were able to deliver papain across the stratum corneum barrier, while papain solution and papain liposomes were not able to cross the barrier. However, transferosomes were not able to deliver papain across the full thickness rat skin model suggesting the deposition of papain loaded transferosomes in the epidermal or dermal layer of skin. In addition, an ex-vivo model was used to analyze the effect of papain exposure on the morphology of the epidermis taken from rat skin exposed to papain solution, papain in transferosomes and papain in liposomes. Papain in solution resulted in a noticeable degradation of the epidermis, but when embedded in either transferosomes or liposomes there was no noticeable change when compared to control animals. The cytotoxicity study performed using HeLa cells showed that the cells were viable at papain concentrations lower than 0.01 mg/ml.

Cephalopod-inspired polymer composites with mechanically tunable infrared properties

Cephalopods have evolved an all-soft skin that can rapidly display colors for protection, predation, or communication. Development of synthetic analogs to mimic such color-changing abilities in the infrared (IR) region is pivotal to a variety of technologies ranging from soft robotics, flexible displays, dynamic thermoregulatory systems, to adaptive IR disguise platforms. However, the integration of tissue-like mechanical properties and rapid IR modulation ability into smart materials remains challenging. Here, by drawing inspiration from cephalopod skin, we develop an all-soft adaptive IR composite that can dynamically change its IR appearance upon equiaxial stretching. The biomimetic composite is built entirely from soft materials of liquid metal droplets and elastic elastomer, which are analogs of chromatophores and dermal layer of cephalopod skin, respectively. Driven by externally applied strains, the liquid metal inclusions transition between a contracted droplet state with corrugated surface and an expanded platelet state with relatively smooth surface, enabling dynamic variations in the IR reflectance/emissivity of the composite and ultimately resulting in reversible IR adaption. Strain-actuated flexible IR displays and pneumatically-driven soft devices that can dynamically manipulate their IR appearance are demonstrated as examples of the applicability of this material in emerging adaptive soft electronics.

Roles of bovine sialoglycoproteins for anti-skin aging and accelerating skin wound healing.

Fibroblasts are the most predominant cell subpopulation in the dermal layer of human skin, they play an important role in maintaining skin architecture and function. The senescence of fibroblasts is one of major causes of skin aging and chronic wound in the elderly, which is accompanied with a reduction of α2,6-sialylation on the cell surface. In this study, we investigated the effects of the bovine sialoglycoproteins on normal human dermal fibroblasts (NHDF). The results showed that bovine sialoglycoproteins could promote the proliferation and migration of NHDF cells, and accelerate the contraction of fibroblast-populated collagen lattice (FPCL). The average doubling time of NHDF cells treated with bovine sialoglycoproteins (0.5 mg/mL) was 31.1 ± 1.0 h whereas that was 37.9 ± 2.7 h for the control (p ˂ 0.05). Moreover, the expression of basic fibroblast growth factor (FGF-2) was upregulated, while that of transforming growth factor-beta 1 (TGF-β1) and human type I collagen (COL-I) were downregulated in treated NHDF cells. Furthermore, bovine sialoglycoproteins treatment significantly enhanced the α2,6-sialylation on the cell surfaces, which was consistent with the upregulation of α2,6-sialyltransferase I (ST6GAL1) expression. These results indicated that the bovine sialoglycoproteins might be developed as a reagent against skin aging in the cosmetic industry, or as a new candidate for accelerating skin wound healing and inhibiting scar formation.

Expression of HSP70 in Human Skin After Cryolipolysis Treatment.

Cryolipolysis nonsurgically targets and reduces subcutaneous fat through controlled cooling of skin and underlying fatty tissue. Although skin changes after cryolipolysis treatment have been observed clinically, the mechanisms by which these occur are not well understood. The aim of this study was to investigate the expression of heat shock protein 70 (HSP70) in the epidermal and dermal layers of human skin following cryolipolysis treatment. Subjects (N = 11; average age, 41.8 years; average BMI, 29.59 kg/m2) were recruited to receive cryolipolysis treatment with a vacuum cooling cup applicator (-11°C/35 minutes) prior to abdominoplasty surgery. Treated and untreated abdominal tissue samples were harvested immediately after surgery (average follow-up, 15 days; range, 3 days to 5 weeks). Immunohistochemistry for HSP70 was performed on all samples. Slides were digitized and quantified in epidermal and dermal layers. There was higher epidermal and dermal HSP70 expression in cryolipolysis-treated pre-abdominoplasty samples vs untreated samples. There was a 1.32-fold increase of HSP70 expression in the epidermis (P < .05) and a 1.92-fold increase in the dermis (P < .04) compared with untreated samples. We found significant induction of HSP70 after cryolipolysis treatment in epidermal and dermal layers. HSP70 has potential therapeutic benefits and is recognized to have a role in skin protection and adaption after thermal stress. Although cryolipolysis is popular for subcutaneous fat reduction, cryolipolytic HSP induction in the skin may prove valuable for additional therapeutic applications, including skin wound healing, remodeling, rejuvenation, and photoprotection.

Co-axial electrospinning of PLLA shell, collagen core nanofibers for skin tissue engineering.

The main functions of wound dressing biomaterials are to promote a moist environment in the wound while protecting the area from mechanical injury and microbial contamination. Furthermore, the scaffold used for skin tissue engineering must mimic epidermal and dermal layers as well as support the growth of keratinocytes and fibroblasts. In this study, PLLA (shell) and EGF-encapsulated collagen (core) nanofibers were produced by coaxial electrospinning at 25 kV potential, 12cm collector distance, and 0.125mL/h flow rate of PLLA (15%) and collagen (4%). The bilayer structure was produced by gelling GeIMA in between two nanofiber membranes to imitate the epidermal and dermal layers of skin. Cytocompatibility properties of nanofiber membrane and bilayer structure were characterized by mono- and coculture of keratinocytes (HaCaT) and fibroblasts (3T3), respectively. TEM revealed that the PLLA shell and collagen core thicknesses were about 60 and 115nm, respectively. Oxygen and water vapor could pass through the GeIMA- integrated bilayer nanofiber membranes. The presence of EGF in nanofibers could increase cell proliferation. Fluorescence and SEM imaging showed that HaCaT and 3T3 could cover the membrane after 14days of monoculture. Cocultures showed a reduction in the proliferation of cells in the first week and a recovery during the second and third weeks. In a mechanical bioreactor, cocultured bilayer membranes formed interlocked polygonal keratinocyte cells. These results showed that the bilayer nanofiber membrane and GeIMA combination provided cell compatibility. Furthermore, the use of a mechanical reactor was found to be effective in the formation of a functional keratinocyte layer by stimulating cells.

The use of ultrasound and magnetic resonance imaging in the management of hidradenitis suppurativa: a narrative review.

Hidradenitis suppurativa (HS) is a chronic, inflammatory follicular skin disease that frequently affects the apocrine gland-bearing skin of the axillary, inguinal and anogenital regions. HS has a significant impact on the psychosocial health and quality of life of patients. Diagnosis of HS is typically clinical, and relies on the ability of physicians to recognize the signs of HS. However, lesions may present at the dermal and subcutaneous skin layers, which cannot be diagnosed by clinical examination alone. Further, the complexity of the clinical presentation of HS can lead to misdiagnosis and delay of diagnosis and appropriate treatment. Imaging is an important tool that can address these issues by detecting inflammatory activity and the early subclinical and dermal features of HS, and accurately characterizing lesional morphology, thereby informing on optimal therapeutic strategies. Overall, imaging is a key tool that can be used in conjunction with clinical examination to improve the management of HS by providing additional information to physicians, and thus optimize clinical decision making. In this narrative review, we provide an overview of the general role of imaging in the management of HS, and we illustrate HS-specific applications of two pertinent imaging modalities, ultrasound and magnetic resonance imaging. Finally, based on the literature, we summarize their uses in HS and provide considerations relating to standardizing the practise of ultrasound and effectively implementing the use of imaging in the management of HS.

The deleterious effect of xylene-induced ear edema in rats: Protective role of dexketoprofen trometamol transdermal invasomes via inhibiting the oxidative stress/NF-κB/COX-2 pathway

Pain and inflammation could have a negative impact on a patient's quality of life and performance, causing them to sleep less. Dexketoprofen trometamol (DKT) is a water-soluble, nonselective NSAIDs. Because DKT is quickly eliminated in the urine after oral delivery, its efficacy is limited and must be taken repeatedly throughout the day. The main ambition of this work is to develop and characterize the potential of invasomes to enhance the transdermal transport of DKT to achieve efficient anti-inflammatory and pain management. The optimum formulation (C1) showed the least %RE (53.29 ± 2.68 %), the highest %EE (86.51 ± 1.05 %), and spherical nanosized vesicles (211.9 ± 0.57 nm) with (PDI) of 0.353 ± 0.01 and (ZP) of −19.15 ± 2.45 mV. DKT flux and deposition in stratum corneum, epidermal, and dermal skin layers were significantly augmented by 2.6 and 3.51 folds, respectively, from the optimum invasomal gel formulation (C1-G) compared to DKT conventional gel (DKT-G). The anti-inflammatory activity of C1-G was evaluated using a model of xylene-induced ear edema in rats. Xylene exposure upregulated the ear expression of COX-2 level and MPO activity. Xylene also significantly increased the ear NF-κB p65, TNF-α, IL-Iβ, and MDA levels. Furthermore, xylene induced oxidative stress, as evidenced by a significant decrease in ear GSH and serum TAC levels. These impacts were drastically improved by applying C1-G compared to rats that received DKT-G and plain invasomal gel formulation (plain C1-G). The histopathological findings imparted substantiation to the biochemical and molecular investigations. Thereby, C1-G could be a promising transdermal drug delivery system to improve the anti-inflammatory and pain management of DKT.

Role of Mechanoinsensitive Nociceptors in Painful Diabetic Peripheral Neuropathy.

The cutaneous mechanisms that trigger spontaneous neuropathic pain in diabetic peripheral neuropathy (PDPN) are far from clear. Two types of nociceptors are found within the epidermal and dermal skin layers. Small-diameter lightly myelinated Aδ and unmyelinated C cutaneous mechano and heat-sensitive (AMH and CMH) and C mechanoinsensitive (CMi) nociceptors transmit pain from the periphery to central nervous system. AMH and CMH fibers are mainly located in the epidermis, and CMi fibers are distributed in the dermis. In DPN, dying back intra-epidermal AMH and CMH fibers leads to reduced pain sensitivity, and the patients exhibit significantly increased pain thresholds to acute pain when tested using traditional methods. The role of CMi fibers in painful neuropathies has not been fully explored. Microneurography has been the only tool to access CMi fibers and differentiate AMH, CMH, and CMi fiber types. Due to the complexity, its use is impractical in clinical settings. In contrast, a newly developed diode laser fiber selective stimulation (DLss) technique allows to safely and selectively stimulate Aδ and C fibers in the superficial and deep skin layers. DLss data demonstrate that patients with painful DPN have increased Aδ fiber pain thresholds, while C-fiber thresholds are intact because, in these patients, CMi fibers are abnormally spontaneously active. It is also possible to determine the involvement of CMi fibers by measuring the area of DLss-induced neurogenic axon reflex flare. The differences in AMH, CMH, and CMi fibers identify patients with painful and painless neuropathy. In this review, we will discuss the role of CMi fibers in PDPN.

Genome-Wide RNA Sequencing Analysis in Human Dermal Fibroblasts Exposed to Low-Dose Ultraviolet A Radiation.

Ultraviolet A (UVA) radiation can pass through the epidermis and reach the dermal skin layer, contributing to photoaging, DNA damage, and photocarcinogenesis in dermal fibroblasts. High-dose UVA exposure induces erythema, whereas low-dose, long-term UVA exposure causes skin damage and cell senescence. Biomarkers for evaluating damage caused by low-dose UVA in fibroblasts are lacking, making it difficult to develop therapeutic agents for skin aging and aging-associated diseases. We performed RNA-sequencing to investigate gene and pathway alterations in low-dose UVA-irradiated human skin-derived NB1RGB primary fibroblasts. Differentially expressed genes were identified and subjected to Gene Ontology and reactome pathway analysis, which revealed enrichment in genes in the senescence-associated secretory phenotype, apoptosis, respiratory electron transport, and transcriptional regulation by tumor suppressor p53 pathways. Insulin-like growth factor binding protein 7 (IGFBP7) showed the lowest p-value in RNA-sequencing analysis and was associated with the senescence-associated secretory phenotype. Protein–protein interaction analysis revealed that Fos proto-oncogene had a high-confidence network with IGFBP7 as transcription factor of the IGFBP7 gene among SASP hit genes, which were validated using RT-qPCR. Because of their high sensitivity to low-dose UVA radiation, Fos and IGFBP7 show potential as biomarkers for evaluating the effect of low-dose UVA radiation on dermal fibroblasts.

Inhibition of Wnt/β‐catenin Signaling Pathway on Melanogenesis‐ Insights from Zebrafish (Danio rerio)

IntroductionVertebrate color patterns are composed of specialized pigment‐producing cells, the chromatophores. Melanin is the main pigment type that colors the skin and skin appendages in mammals. Melanin is produced by specialized cells called melanocytes. Melanocytes have embryonic neural crest cells origin and their development and functions are ubiquitous across vertebrates, residing in dermal and epidermal skin layers. Studies of melanogenesis have provided experimentalists with a valuable system for understanding pattern formation in the developing embryo. In addition, studying these mechanisms may have important consequences for the clinical sciences. Alcohol is a widely abused teratogenic substance. Fetal alcohol spectrum disorder (FASD) is described as birth defects associated with prenatal alcohol exposure (PAE). PAE is likely one of the leading causes of birth defects but pathophysiology of FASD associated body pigmentation disorders are needed to be investigated further. Zebrafish (Danio rerio) (ZF) is identified as a good model to study FASD and melanocyte biology. Wnt signaling pathway is a conserved signal transduction pathway which is important in embryonic development and it regulates many aspects of melanogenesis. The current study was designed to investigate the effect of Alcohol‐Wnt signaling pathway activity on ZF melanogenesis.Materials and MethodsWild‐type (WT) ZF embryos were treated with Wnt pathway inhibitor (LiCl) and combined chemical treatment (LiCl and 1% alcohol) at 10 hours post fertilization (hpf). The differential effects of above substances on early development, differentiation, patterning of melanocytes were investigated using cell biology and imaging techniques.ResultsMelanocytes of LiCl exposed samples showed defects in migration, arrangement and survival. Ectopic melanocytes and developmental aberrations of eye pigmentation were noticed in both chemical treatments. Significant variation of the melanocyte cell size, shape and body pigmentation patterning was observed among the LiCl and combined treated samples compared to the control.ConclusionEmbryonic LiCl and alcohol exposures affect the development and patterning of the melanocytes in ZF. The molecular mechanisms underlying the above phenotypes will be investigated further to understand the FASD associated pigmentation defects.

Augmented local skin accumulation efficiency of sertaconazole nitrate via glycerosomal hydrogel: Formulation, statistical optimization, ex vivo performance and in vivo penetration

This study aimed at formulating Sertaconazole nitrate (SZ), in a suitable glycerosomes based topical formulation that offers deep skin penetration and high local skin accumulation efficiency. SZ Glycerosomes were prepared using thin-film hydration technique according to a 24 full factorial design. Studied factors were Phosphatidylcholine (PhC) amount, Brij® L4: PhC ratio, glycerol concentration, and method of further treatment either sonication or freezing and thawing. The power of the design for each response was calculated before design implementation. Suitable models were elucidated for studied responses and their validity was checked. An optimized formula (O-GL) was numerically optimized using Design expert software®. The O-GL had suitable characterization with entrapment efficiency of 80.6 ± 2.9%, particle size of 418 ± 11 nm, polydispersity index of 0.452 ± 0.27, and zeta potential of −52.6 ± 0.6 mV. This O-GL was incorporated in a hydrogel (O-GL hydrogel). This O-GL hydrogel showed superior ex-vivo deposition in rat skin (Local accumulation efficiency: 55.1 ± 7.9) compared to O-GL (14.9 ± 1.1) and Dermofix® cream (marketed product) (13.1 ± 0.8). It also showed deep in-vivo penetration that reached deep dermal skin layers. Thus, the proposed formula (O-GL hydrogel) is promising for SZ topical delivery. It achieved deep skin penetration and high local skin accumulation efficiency for the effective treatment of fungal infections.

Lateral Dermal Penetration Is Dependent on the Lipophilicity of Active Ingredients

Introduction: With its large surface area, skin facilitates a topical administration of active ingredients, and thus percutaneous delivery to a specific target site. Due to its high barrier function and different diffusion characteristics, skin governs the efficacy of these active ingredients and a bioavailability in the epidermal and dermal tissue. Objective: In order to characterize the vertical and lateral movement of molecules into and inside the skin, the diffusivity of active ingredients with different physicochemical properties and their penetration ability in different dermal skin layers was investigated. Methods: A novel lateral dermal microdialysis (MD) penetration setup was used to compare the diffusion characteristics of active ingredients into superficial and deep-implanted MD membranes in porcine skin. The corresponding membrane depth was determined via ultrasound and the active ingredients concentration via high-pressure liquid chromatography measurement. Results: The depth depended penetration of superficial and deep-implanted MD membranes and the quantitative diffusivity of two active ingredients was compared. An experimental lateral MD setup was used to determine the influence of percutaneous skin penetration characteristics of an active ingredient with different lipophilic and hydrophilic characteristics. Therefore, hydrophilic caffeine and lipophilic LIP1, which have an identical molecular weight but different lipophilic characteristics, were tested for their penetration ability inside a propylene glycol and oleic acid formulation. Conclusion: The vertical and lateral penetration movement of caffeine was found to exceed that of LIP1 through the hydrophilic dermal environment. The findings of this study show that the lipophilicity of active ingredients influences the penetration movement and that skin enables a conical increasing lateral diffusivity and transdermal delivery.

Associations between skin structural and functional changes after loading in healthy aged females at sacral and heel skin: A secondary data analysis

Aim of the studyMechanical loading causes skin occlusion and deformation, which influences structural and functional skin properties. Aims of the study were to measure structural and functional skin parameters after loading at the sacral and heel skin and to describe possible associations. Material and methodsA secondary data analysis based on a clinical trial with n = 15 aged women was conducted. Changes of transepidermal water loss, stratum corneum hydration, epidermal hydration, erythema, temperature, structural stiffness, elastic recovery, elastic function, and mean roughness after 120 min loading were described and compared. Spearman's rho (rs) was used to estimate possible associations. ResultsLoading caused an increase of transepidermal water loss, stratum corneum and epidermal hydration, erythema and temperature at sacral and heel skin. There was a decrease of median roughness at the heel skin surface (-8.5 (IQR -10.5 to 5.5) μm). Strongest positive associations were observed between changes of elastic function and elastic recovery (rs = 0.9 at heel and sacral skin) and between changes of epidermal and stratum corneum hydration at both skin areas (rs = 0.7 at sacral skin and rs = 0.5 at the heel). ConclusionTwo hours loading on a standard foam mattress leads to skin occlusion at the skin surface and mechanical deformation. Skin occlusion seems primarily to increase temperature, stratum corneum and epidermal hydration that may affect mechanical skin properties. Mechanical deformation seems to be responsible for the erythematous response of the dermal skin layer.