Skin Pharmacology and Physiology最新文献

Background: Curcumin is a polyphenolic compound present in turmeric (Curcuma longa). Curcumin, turmeric powder, and extracts are widely used in traditional Indian medicine and are active ingredients of dietary supplements and cosmeceutical products. The pharmacological properties of curcumin/turmeric as well as the studies performed in vitro, in animal models, and in volunteers have been the objects of a vast literature. Most of the clinical studies report on the effects of curcumin/turmeric administered orally, while only a few describe its topical applications.

Summary: This review focuses on clinical studies in which curcumin/turmeric was applied topically to treat various skin conditions based on its antioxidant, anti-inflammatory, and antimicrobial properties.

Key messages: The clinical studies employing curcumin/turmeric as the only active ingredient allow us to appreciate its therapeutic potential without confounding contributions coming from additional pharmacologically active substances present in the same formulation. Curcumin/turmeric was regarded as an attractive alternative to conventional drugs, such as corticosteroids and antibiotics, thanks to its characteristics of a safe and well-tolerated natural substance.

Autism is a neurodevelopmental disorder. Individuals with autism can exhibit multiple neurological symptoms such as deficit in social communication, restricted interests, and repetitive behaviors. Recent study showed that murine model of autism displays an increased transepidermal water loss (TEWL) and dry skin. But whether epidermal functions are also altered in children with autism is unknown. In the present study, TEWL, stratum corneum hydration, and skin surface pH were compared between children with autism (N = 56) and normal controls (N = 48). Our results showed that children with autism exhibited lower stratum corneum hydration levels, higher TEWL, and elevated skin surface pH in comparison to normal controls (p < 0.0001 for all). These results demonstrate that children with autism exhibit epidermal dysfunction.

Background: Obesity is a condition defined by an excess amount of body fat, with body mass index (BMI) of 30 and higher. It is associated with a number of other medical conditions, including insulin resistance, diabetes mellitus, and cardiovascular diseases, as well as dyslipidemia, and it is also associated with several cutaneous disorders such as atopic dermatitis, psoriasis, intertriginous dermatitis, acanthosis nigricans and skin infections.

Summary: Evidence suggests a link between obesity and epidermal dysfunction. Generally, individuals with obesity display higher transepidermal water loss rate and lower stratum corneum hydration levels, although no association of obesity with epidermal dysfunction has been documented. Results of skin surface pH are controversial. But study demonstrated a positive correlation of BMI with skin surface pH on both the forearm and the shin in males, suggesting that the changes in epidermal function vary with gender in individuals with obesity.

Key messages: This review summarizes the association between obesity and epidermal function, and discusses possible underlying mechanisms. Individuals with obesity exhibit poor epidermal permeability barrier and lower stratum corneum hydration levels. Because of the pathogenic role of compromised epidermal function in inflammation, which is also linked to obesity, improvement in epidermal function could benefit individuals with obesity, particularly those with abnormalities in epidermal function.

Background: For one half-century, cultures of human epidermal keratinocytes have opened new paths of research in skin biology and dermatology. Either performed with serum and feeder layer, in serum-free conditions, or in autocrine conditions, cells cultured as monolayers became research materials for basic science and dermatology, as well as a source for grafting, particularly to treat severely burned patients. More recently, tissue reconstruction at air-liquid interface has opened new perspectives for in vitro toxicology, studies of epidermal barrier, and modeling skin diseases.

Summary: This review presents a brief retrospective of the emergence of keratinocyte-based culture techniques. It also presents opportunities and eventual problems that researchers might encounter when exploring the skin using such procedures.

Key messages: While methodologies in tissue culture evolve, the multiplicity of procedures concomitantly increases, requiring to make some selective but difficult choice. Keeping tracks of technological evolution in epidermal cell culture should help choosing the adequate methodology for a specific investigation or innovating with new, more dedicated ones.

Introduction: The stratum corneum (SC) matrix is composed of free fatty acids, cholesterol, and ceramides (CERs), which play a key role in the skin barrier function. Changes in the composition and content of skin lipids will affect the function of the skin barrier. The effect of a glycerol/petrolatum-based emollient (G/P-emollient) cream on the lipid profiles of isolated ex vivo human SC and the SC of a reconstructed human epidermis (RHE) model was measured.

Methods: The spatial organization of the cream and the isolated SC intercellular matrix were studied using X-ray diffraction. The inter-bilayer distances in the multi-lamellar lipid structures and lattice type were analyzed using small-angle X-ray scattering and wide-angle X-ray scattering (WAXS), respectively. Lipidomic analysis using shotgun lipidomics was performed on RHE models to quantify CER classes and chain lengths. This technology enables the analysis of thousands of lipids in a single biological sample.

Results: The crystallized components of the cream are lipids, which were mainly packed in orthorhombic lattices, as well as hexagonal lattices and were similar to the SC structure. The cream penetrated the SC but did not alter the WAXS profile. It increased the amount of higher carbon number CERs (>42 carbons) and decreased lower carbon number CERs (<42 carbons). All chain length of CERs and acyl-CER classes (CER EOS, EOH, EOP, EOdS) were increased as the total CER classes. A decrease of the CER C34 for hydroxylated and non-hydroxylated CERs was also observed. The cream altered the S and P CER forms (increased the NP/NS and AP/AS ratios), indicating it could reduce the relative feedback mechanism observed in inflammatory pathologies, for example, atopic dermatitis. The cream increased CER NP, which is decreased in dry skin.

Conclusion: G/P-emollient cream may be beneficial for skin pathologies by modifying SC lipids, balancing CER levels and ratios, and improving the barrier function. Importantly, the cream structure mimics that of the SC and penetrated the lower SC layers without compromising its lamellar structure.

Introduction: The role of bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exo) in skin photoaging was explored in human dermal fibroblasts (HDFs). The underlying mechanism was further explored.

Methods: HDFs were exposed to UVB irradiation to establish the cell photodamage models. The cell viability and levels of oxidative stress-related factors were tested. ELISA was done to detect TNF-α, IL-6, and IL-1β concentrations. Western blot was applied for protein examination.

Results: UVB treatment led to the inhibition of cell viability. But after BMSCs-exo addition, the inhibitory effect was returned in a dose manner. UVB exposure contributed to the increase of reactive oxygen species and LDH and the downregulation of superoxide dismutase. In addition, excessive secretion of TNF-α, IL-6, and IL-1β was also detected in cells exposed to UVB. However, BMSCs-exo addition eliminated the effects of UVB on oxidative stress and inflammation in HDFs. BMSCs-exo inhibited matrix metalloproteinases MMP-1 and MMP-3 expression but promoted collagen I expression. UVB radiation activated the MAPK/AP-1 signaling, manifested as the increase of p-p38, c-Jun, and c-Fos protein levels, which were reversed by BMSCs-exo. As a p38 agonist, anisomycin counteracted the effect of BMSCs-exo on HDF's viability, oxidative stress, and inflammation.

Conclusion: BMSCs-exo protected HDFs against UVB-induced inhibition of cell viability and the activation of cell oxidative stress and inflammation, which might be related to the inhibition of the MAPK/AP-1 signaling pathway.

Introduction: Skin prick tests have a long history as diagnostic and pharmacodynamic biomarker. Besides visual assessments of the wheal and flare, objective blood flow measurements using laser Doppler imaging (LDI) and laser speckle contrast imaging (LSCI) have been reported. In light of these advancements, an up-to-date characterization of the histamine-evoked response is worthwhile.

Methods: A single-centre study was completed in healthy males. Two parameters were addressed: (1) dermal blood flow (DBF) within a 7.65-mm ring encircling the skin prick site (DBFring), and (2) surface area of the flare (AREAflare). First, the dose response was assessed using placebo (0.9% sodium chloride) or histamine (histamine dihydrochloride 1, 3, or 10 mg/mL) skin pricks on the volar surface of subjects' (n = 12) forearm. The DBFring was measured by LDI, and the AREAflare by LDI and by ruler. Secondly, the inter-arm and inter-period reproducibility of the DBFring and AREAflare, as evoked by histamine (10 mg/mL) and measured by LDI and LSCI, was examined (n = 14). Lastly, the effect of aprepitant (125 mg), ketotifen (1 mg), and a single (5 mg) and fourfold (20 mg) dose of desloratadine and levocetirizine on the histamine-induced (10 mg/mL) DBFring and AREAflare was evaluated with LSCI (n = 13 or 12).

Results: All three histamine doses induced a time-dependent vasodilation. Ruler recordings did not conclusively correlate with LDI assessments of the AREAflare. The DBFring and AREAflare were reasonably reproducible when measured by using LDI or LSCI, with negligible bias between arms and study periods and poor to moderate within-subject reproducibility (0.23 ≤ ICC ≤ 0.71). While the fourfold dose of desloratadine (p = 0.0041) and the single and fourfold dose of levocetirizine (p < 0.0001) managed to reduce the AREAflare, only the fourfold dose of levocetirizine (p = 0.0052) reduced the DBFring.

Conclusion: Caution is warranted when translating years of clinical experience with histamine skin prick tests to objective recordings of the associated changes in skin perfusion. Ruler and LDI assessments of the AREAflare do not consistently correlate, and the reproducibility and histamine dependency of the measurements are not obvious. While 10 mg/mL histamine may be a good choice for qualitative diagnostic evaluations, a lower dose may be better suited to use as a quantitative biomarker.

Introduction: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls.

Methods: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented.

Results: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded.

Conclusion: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism.

Introduction: Proteins, such as cytokines and chemokines, are present in varying concentrations in a range of biofluids, with an important signalling role in maintaining homeostasis. Commercial tapes have been employed to non-invasively collect these potential biomarkers in sebum from the skin surface to examine their concentrations in conditions including acne, atopic dermatitis, and pressure ulcers. However, the identification of robust biomarker candidates is limited by the low abundance of specific proteins extracted by current methodologies. Therefore, this study was designed to develop an optimized extraction method for potential inflammatory biomarkers in sebum collected with Sebutapes.

Methods: Commercial tapes (Sebutapes) coated with synthetic sebum were used to systematically evaluate the effects of chemical and mechanical stimuli on extraction efficiency. Varying concentrations of high- and low-abundance biomarkers (IL-1α, IL-6, IL-8, INF-γ, TNF-α, and IL-1RA) were used to spike the synthetic sebum samples. Methodological variables included different surfactants, mechanical stimuli, and buffer volume. Extraction efficiency was estimated using immunoassay kits from the extracted buffer.

Results: The results revealed that the use of a surfactant, i.e., β-dodecyl maltoside, in addition to the mechanical stimuli, namely, sonication and centrifugation, resulted in an increased recovery of cytokines, ranging from 80% for high-abundant cytokines, such as IL-1α and IL-1RA, and up to 50% for low-abundance cytokines, including TNF-α, IL-6 and IL-8. Compared to previous methods, the new extraction protocol resulted in between a 1.5-2.0-fold increase in extraction efficiency.

Conclusion: The study revealed that there was a high degree of variability in the extraction efficiency of different cytokines. However, improved efficiency was achieved across all cytokines with selective surfactants and mechanical stimuli. The optimised protocol will provide means to detect low levels of potential biomarkers from skin surface, enabling the evaluation of local changes in pro- and anti-inflammatory cytokines present in different skin conditions.

Background: Trichoscopy is a simple, noninvasive procedure practiced in the diagnosis of a multitude of scalp and hair disorders. Hair shaft abnormalities usually represent a diagnostic challenge to dermatologists.

Objectives: The aim of the study was to determine the practicality, versatility, and value of using the handheld dermoscope in the assessment of hair shaft abnormalities and the diagnosis of different hair/scalp disorders.

Methods: Eight hundred and seven patients of both sexes, aged from 1 to 76 years, with complaints pertaining to scalp and hair, were the subjects of the study. All patients were examined by the handheld dermoscope, and 400 were additionally examined by the folliscope, digital dermoscope, or their hairs mounted for light microscopy.

Results: Based on trichoscopic findings, more than half the patients demonstrated thinned terminal hairs and a predominance of single-haired scalp pilosebaceous units (57% and 55.5%, respectively). Over a quarter of the patients showed hair diameter heterogeneity, upright regrowing hairs, and increased vellus hairs (37%, 31%, and 25%, respectively). Other trichoscopic findings included scalp scaling (19%), hair weathering (12%), thinned wavy hairs (10.5%), brush-like hair fractures (9%), exclamation mark hairs (9%), and longitudinal cleavage (trichoptilosis) (8%). The clinical diagnostic spectrum was topped by the following diagnoses in order of frequency: female pattern hair loss, telogen effluvium, traction alopecia, and trichotillomania. Trichodynia appeared to be significantly associated with numerous hair shaft abnormalities.

Conclusion: Most hair shaft abnormalities can be reliably diagnosed with high accuracy using a handheld dermoscope in an office setting. Skillful knowledge of dermoscopy is an important aid in the diagnosis of hair and scalp disorders.