Skin Pharmacology and Physiology最新文献

Introduction: Loss of skin integrity due to a wound or disease can lead to severe disability or even life threat. The highly expressed microRNAs in the skin are of great significance for skin development. The investigation purposed to explore the effect and mechanism of miR-211 on inflammation, oxidative stress and migration in keratinocytes.

Methods: The HaCaT keratinocytes were treated with hydrogen peroxide (H2O2) to establish a wound-healing model. The expression of miR-211 was examined by quantitative real-time PCR (qRT-PCR). The cell function was reflected in proliferative ability, migration, apoptosis, and inflammation, which were evaluated by Cell Counting Kit-8 (CCK-8) assay, Transwell test, flow cytometry technique, and enzyme-linked immunosorbent assay (ELISA). The target of miR-211 was verified by luciferase luminescence measurements.

Results: H2O2 inhibited HaCaT cell proliferation, migration, and promoted cell apoptosis, accompanied with the downregulation of miR-211. H2O2 led to inflammatory response and oxidative damage to HaCaT. MiR-211 promoted proliferation and migration, but improved cell apoptosis of HaCaT. The role of H2O2 on inflammatory response and oxidative stress was alleviated by miR-211. SRY-box transcription factor 11 (SOX11) was a targeted mediator of miR-211. SOX11 reversed the influence of miR-211 on cell proliferation, migration, apoptosis, inflammatory response and oxidative stress.

Conclusion: MiR-211 regulated proliferation, migration, apoptosis, inflammation and oxidative stress of keratinocytes by mediating SOX11, thus participating in cutaneous wound healing.

Introduction: Emollients are part of daily body care and have become indispensable therapeutic adjuvants for the treatment of dry skin conditions. Adherence to topical treatments, notably for dry skin conditions, has been reported to be low. The underlying reasons may include insufficient medical and nursing support for product selection, specific product attributes, aspects of product application, and product feel on the skin. Attempts have also been made to portray lipid content, galenic product format, or rheological attributes (pharmaceutical attributes) as adherence-promoting or adherence-preventing properties. In the treatment of dry dermatoses with emollients, there is little information describing and relating to these various features. We explored whether the sensory attributes of selected emollients were associated with common product attributes such as lipid content, viscosity, or galenic product format, and discuss the extent to which this information is useful for product selection.

Methods: Nine trained panellists evaluated ten selected emollients based on a set of 18 predefined sensory attributes according to a standard guide for sensory descriptive analysis. Viscosity was determined using a rotational rheometer.

Results: The emollients had product-specific sensory attributes. Lipid content, viscosity, and galenic product format are not generally indicative of sensory product attributes.

Conclusions: Contrary to popular belief, lipid content and viscosity are not generally indicative of sensory product attributes. This is mainly due to the different physicochemical properties of the lipid phase ingredients, which are product-specific and diverse. As most emollients contain significant amounts of volatile ingredients that evaporate during and after application, their galenic format changes dramatically. Therefore, this is not a viable selection criterion. Because refined information on sensory product attributes, as compiled for this study, is rarely available in everyday life, eliciting individual and subjective patient preferences through dialogue remains crucial. Ideally, patient preferences can be elicited from the sample packs.

Introduction: Previous studies have investigated the density of dermal papillae (DP) in normal skin using reflectance confocal microscopy (RCM), a non-invasive imaging technique that allows a real time, high-resolution imaging of the skin, although no histological confirmation was provided. The aim of the present study was to compare the RCM evaluation of DP density in healthy skin with horizontal histopathological sections (HHS), a technique that provides a horizontal view of the skin.

Methods: Ten adult patients were selected, and a healthy skin area was marked for RCM examination and a subsequent 5-mm punch biopsy that was processed for HHS. Two different blinded operators performed DP counting on RCM and HHS images, respectively.

Results: A total of 10 skin samples were obtained from the lower back. The mean DP density resulting from RCM was 84.27±3.24/mm2, while that from HHS was 84.08±2.74/mm2. Student T-test showed no significant differences in DP count between the two techniques (P=0.89).

Discussion: The strength of this study is represented by the histological evaluation which has never been previously performed, whose results align with the RCM findings and validate previous data from our group, with negligible differences. We believe that the exact identification of the DP number in normal skin may have practical implications, as several inflammatory skin conditions are characterized by DP changes such as psoriasis, lichen planus, and discoid lupus.

Introduction: Turpentine derivatives and eucalyptus oil are herbal substances traditionally used to treat various skin infections. Limited non-clinical data suggest they exert an immunological activity, but only scant information exists on their antibiotic effects. This in vitro study has been carried out to investigate the antibacterial and antifungal activity of a marketed skin ointment; its active pharmaceutical ingredients larch turpentine, eucalyptus oil, and turpentine oil; and their mixture, against bacteria and yeasts commonly present on the skin and causing skin infections.

Methods: The antibiotic activity was tested using the drop dilution assay on the Gram-positive bacteria Staphylococcus aureus (wild type), a methicillin-resistant S. aureus strain, S. epidermidis, S. haemolyticus, Streptococcus pyogenes, the Gram-negative Pseudomonas aeruginosa, and the yeasts Candida albicans and C. tropicalis.

Results: The ointment exerts a strong inhibitory effect on all Gram-positive bacteria at a concentration of 5 g/100 mL in the Müller-Hinton medium. It also has inhibiting effect on both Candida species but does not inhibit P. aeruginosa growth. As for the single active pharmaceutical ingredients, larch turpentine was the most active substance. The mixture of the three ingredients, in the concentrations used in the ointment, had a higher antibiotic effect than any of the individual ingredients studied, suggesting at least an additive activity.

Conclusions: Our study has shown that the herbal ingredients and their combination exert antimicrobial activities, especially against Gram-positive bacteria, that justify their use in the treatment of skin infections.

Background: Alopecia areata (AA) is a T-cell-mediated autoimmune disease that significantly impacts patient quality of life. The breakdown of hair follicle immune privilege underlies AA pathogenesis. However, the precise mechanism of this breakdown remains unclear. This study investigates the potential role of reactive oxygen species in AA pathogenesis.

Summary: A systematic review and meta-analysis were conducted on observational studies and randomized controlled trials from 2000 to 2024. Studies included AA patients and measured oxidative stress index (OSI), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), or paraoxonase-1 (PON1). Extracted data were analyzed using the Cochrane risk-of-bias tool and random-effects models. The review included 21 studies with 743 AA patients. OSI was elevated in AA patients (effect size = 1.58, 95% CI: 0.31-2.68, p = 0.00068). MDA levels were also elevated (effect size = 1.60, 95% CI: 0.43-2.6, p = 0.00023), while SOD (effect size = -0.97, 95% CI: -1.65 to -0.30, p = 0.00066) and GSH-Px (effect size = -1.41, 95% CI: -2.28 to -0.53, p = 0.00068) activities were reduced. PON1 levels showed no significant difference (effect size = -3.56, 95% CI: -8.63 to 1.51, p = 0.051).

Key messages: The elevated OSI and MDA, and decreased antioxidant activity in AA patients suggest a substantial role for reactive oxygen species and oxidative stress in AA pathogenesis, highlighting oxidative stress as a potential target for therapeutic intervention. These results underscore the importance of oxidative stress in AA and support further research into antioxidant-based therapies.

Background: Human life is based on oxygen respiration and an enzymatic, free radical-dependent water chemistry, whose billions of parallel reactions take place at pH ∼7.4 and a temperature of 37°C, in accordance with the laws of chemistry. The cellular metabolic processes occur over time periods covered by the half-lives of reactive oxygen species (ROS) for °OH to over 10 s for lipid oxygen species (LOS), indicating that mixtures of free radicals form the basic components for these processes.

Summary: The main source of radicals is the mitochondrial conversion of 1-5% oxygen into "primary" ROS and "secondary" LOS. Every endogenous and exogenous radical generation, triggered by "natural background radiation," "natural environment," or "solar radiation" leads to qualitatively similar mixtures of "primary" ROS and "secondary" LOS or RNS (reactive nitrogen species). A Multilevel Antioxidant Regulation, Repair and Protection System (MARRPS) keeps these radical mixtures in a steady state. Depending on the total number of free radicals, different areas of radical action are defined. The Free Radical Ground State (FRGS) with "homeostasis" and "adaptive homeostasis," the Free Radical Threshold Value (FRTV), and Free Radical Pathological Conditions (FRPC). The quantitative ratio ROS > LOS comprehensively characterizes the "'homeostasis" and "adaptive homeostasis" area of the FRGS. The total number of free radicals cannot be measured directly in the "homeostasis" area. "Adaptive homeostasis" is achieved when excess radicals are stable produced beyond "homeostasis" of the FRGS. The quantity that remains controllable in this range is a maximum of ∼3.58 × 1012 radicals/mg, the value of the body constant FRTV. The sensitized MARRPS provides "semi-stable homeostatic" states characterized by dual stability with ROS > LOS and a stable total ROS/LOS and RNS count beyond the basal FRGS "homeostasis." If the total number of all radicals exceeds the FRTV, where LOS > ROS, this initiates uncontrolled radical chain reactions. The partial failure of the MARRPS in the FRPC area leads to pathological processes which are the starting point for a hundred different diseases.

Key messages: The universal body constant FRTV is the basis for all regular life processes. The design principle described by this simple model applies universally to all aerobic life.

Introduction: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated.

Methods: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin.

Results: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin.

Conclusion: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin.

Introduction: Increased skin pH values in patients with atopic dermatitis (AD) contribute to poor antimicrobial and permeability barrier functions of the skin. In practice, the majority of topical preparations available for dry skin conditions do not provide sufficient pH and buffering capacity for maintaining optimum skin surface conditions. To address this issue, we tested a novel zinc lactobionate preparation to determine whether the regular application would lower skin surface pH, and in doing so improve the condition of lesional skin.

Methods: The assessment for local severity of AD was done with the Scoring Atopic Dermatitis Index (SCORAD) and skin dryness was assessed by capacitance measurement.

Results: The results showed that the test product lowered skin pH and improved AD skin lesions from moderate to mild during 2 weeks of application. In the treated area a lowered pH of about 0.85 units was found. Together with the lowering of pH, the local SCORAD significantly improved from 8.3 on average down to 4.0, while in the untreated area, only a slight improvement (from 8.2 to 6.4) was found.

Conclusion: Synergistic effects of the test product's pH lowering and emollient properties might explain the observed improvements in clinical signs of AD and further research against a comparator would allow the specific contribution of pH modulation to these improvements to be unambiguously isolated.

Introduction: Skin-blanching assay has been established as a surrogate method for assessing bioequivalence of topical corticosteroids. This study aimed to apply the skin-blanching assay to evaluate the bioequivalence of a test desonide cream (T) compared with the reference Desonide® (R) using Chinese skins. Additionally, the pharmacokinetics and safety profiles were also assessed.

Methods: By detecting the degree of skin blanching under different dose durations in a pilot dose-duration-response study, the area under the observed effect-time curve (AUEC) and half of the maximum effect (ED50) was calculated. Based on this, the skin color of different time points after a dose duration of ED50, D1 (0.5 × ED50), and D2 (2 × ED50) were detected as a pharmacodynamic indicator to compare between test and reference creams. Single-center, single-dose, randomized, open-label, two-cycle crossover pharmacokinetic studies were designed to make sure the exposure of tested formulationswas not higher than that of the reference formulations. Subjects experiencing adverse events (AEs) were monitored and utilized for safety analysis.

Results: These studies involved 12 subjects for the dose-duration-response study, 100 subjects for the bioequivalence study, and 12 subjects for the pharmacokinetic study. The results showed that the population ED50 was 0.88 ± 0.45 h; the mean ratio of area under effective curve from 0 to 24 h (AUEC0-24h) of test and reference preparations was 0.95, with a 90% confidence interval as 88.09-101.72%, indicating the bioequivalence of the test formulation and Desonide®. The maximum plasma concentration (Cmax) and area under the concentration time curve from time 0 to the last time point (AUC0-t) of T and R were 20.8 ± 11.5 pg/mL versus 19.7 ± 10.1 pg/mL, respectively, and 451.04 ± 363.65 pgh/mL versus 541.47 ± 581.41 pgh/mL, respectively. The systemic exposure of a single dose of the test cream was not higher than that of the reference preparation. All of the volunteers experienced grade 1 AEs, suggesting that single administration of the test desonide cream is well tolerated in the Chinese healthy population.

Conclusions: This study demonstrated the applicability of skin-blanching assay in Chinese skins and established the bioequivalence of test and reference desonide creams.