Skin Pharmacology and Physiology最新文献

Introduction: In patients with diabetes, persistent hyperglycemia causes chemical changes in serum components, increasing the incidence of various complications such as skin wounds. To better understand glucose-associated chemical stress on serum components, this study explores small-molecule nutrients to protect human dermal fibroblasts (HDFs) from glucose-rich, chemically deteriorated culture conditions.

Methods: Various cell culture media with different concentrations of glucose and various test compounds were subjected to prolonged heat treatment as a chemically accelerated model of serum deterioration. The heat-treated and non-heat-treated media were compared to each other in terms of the content of glycation products and their effects on cell viability and wound healing.

Results: There was no difference in the content of glycation products or their effects on cell viability between the non-heat-treated low-glucose (LG, 5.5 mM) and high-glucose (HG, 50 mM) media that were not heat-treated. However, the heat-treated HG media had a higher content of glycation products and decreased cell viability compared to the heat-treated LG media. Of the 20 free amino acids, 20 amidated amino acids, and various antioxidants derived from cysteine (Cys) or ascorbic acid (AA) added to the media, followed by heat treatment, only cysteinamide (C-NH2) enhanced the viability and wound healing of HDFs cultured in the heat-treated HG media. C-NH₂ reduced glycation of serum proteins while forming its own glycation products, suggesting a competitive interaction with glucose-derived reactions.

Conclusion: These findings provide proof-of-concept evidence that C-NH2 can protect serum components and improve fibroblast-associated wound closure under chemically stressed, glucose-rich conditions. Further studies using physiologically relevant models are required to evaluate its biological and translational significance.

Introduction: Effective management of atopic dermatitis (AD) remains challenging, as current therapies often rely on topical corticosteroids associated with adverse effects and limited long-term tolerability.

Methods: This double-blind, randomized, placebo-controlled trial investigated the effects of a 12-week oral supplementation with specific bioactive collagen peptides (BCP, CURADERM®) on clinical symptoms and skin physiology in adults with moderate AD. Participants were randomized to receive either 5 g of BCP or placebo daily.

Results: BCP supplementation led to significantly lower corticosteroid rescue medication use (0.94 ± 1.42 g vs. 5.60 ± 7.82 g; p = 0.045; d = 0.847) and an earlier reduction in pruritus, as shown by improvements in the 5-D Pruritus Scale at week 4 (p = 0.024, d = 1.49). Favourable effects were also observed for key physiological parameters of the skin, including maintenance of physiological pH (4.5-5.5) and improved hydration of lesional areas (p = 0.040, d = 1.44). No treatment-related adverse events occurred.

Conclusion: Taken together, these findings provide first placebo-controlled evidence that oral BCP supplementation supports skin barrier recovery, stabilizes physiological skin function, and accelerates symptom relief in mild-to-moderate AD. Confirmation of these promising results in larger trials are warranted to validate treatment effects.

Introduction: Sensitive skin is a common skin condition that impairs quality of life and is characterised by unpleasant sensations to normally non-irritating stimuli. Restoration of skin barrier integrity can relieve symptoms, and accumulating evidence indicates a contributory role of the skin microbiome not only in barrier function but also as a potential modulator in sensitive skin. Ceramide-containing emollients improve barrier function and may modulate microbial communities via restoration of stratum corneum lipids, hydration, and immune regulation.

Methods: In this randomized, double-blind, vehicle-controlled trial, an emollient containing Ceramide NP C15 was evaluated for its effects on sensitive skin symptoms and skin barrier function. Fifty participants applied the study products in a split-body design for six weeks. Primary assessments included skin physiology and symptom burden. Furthermore, skin microbiota changes were explored using flow cytometry (FC)-based bacterial profiling and 16s rRNA gene sequencing.

Results: Both the Ceramide NP C15 formulation and the vehicle were associated with improvements in subjective symptoms. In participants with impaired skin barrier, treatment with the ceramide formulation was associated with a significant reduction in transepidermal water loss. FC- and 16S-based analyses indicated modest, treatment-associated changes in skin microbiota composition including an early and sustained increase in microbial evenness and a significant enrichment of Bifidobacterium.

Conclusion: In this exploratory, randomized controlled study, a Ceramide NP C15-containing emollient was associated with improvements in skin barrier function. Exploratory microbiome analyses suggested treatment-associated changes in microbial community characteristics, which should prompt further investigations in their clinical relevance for sensitive skin.

Introduction: Silymarin (SM), an extract from the fruits of the milk thistle (Silybum marianum L., Asteraceae) has pleiotropic effects on human health. SM's biological activity assigns to its constitutive polyphenols, mainly flavonolignans. SM has become increasingly interesting for dermal applications. There are currently several commercial dermatological preparations available on the market containing SM or its dominant flavonolignan silybin (SB) as the active ingredients. The metabolic transformation of compounds in skin including SM's polyphenols has only been marginally investigated. Therefore, this study focused on the metabolization of SM and its pure polyphenols (SB, isosilybin (ISB), 2,3-dehydrosilybin (DHSB), silychristin (SC), silydianin (SD) and taxifolin (TA)) in the skin.

Methods: Human skin ex vivo (HSE) and normal human dermal fibroblasts (NHDF) were used as experimental models. For cell treatment, a concentration of 10 M (pure compounds) or 4.825 mg L-1 (SM) was used. For HSE treatment, 50 M (pure compounds) or 24.124 mg L-1 (SM) was used.

Results: The penetration of studied polyphenols into the skin correlated with their lipophilicity (DHSBISBSBSCSDTA). The bioavailability of SM's polyphenols was relatively high, and thus the substances can be expected to modulate biological processes in the region close to their application site. SM's polyphenol metabolites of the first and second phase of biotransformation were identified in NHDF and HSE.

Conclusion: In HSE, the metabolic transformation of SM's components and its pure polyphenols was more extensive, as skin fragments are a more complex cellular and metabolically active system. Human skin ex vivo seems to be a useful tool for studying compounds biotransformation at topical application.

Skin hydration, which is defined by the hydration index and the spatial distribution of water, represents one of the key parameters reflecting the functional state of the skin. Although various optical methods have been proposed to study the hydration process, these techniques are often limited by a shallow probing depth, insufficient depth resolution, or low spatial and temporal resolution, which precludes a comprehensive assessment of the skin response to topical pharmaceutical agents. Here, we present an approach for the quantitative assessment and visualization of skin dehydration and rehydration processes with high depth and temporal resolutions. The proposed method is based on reconstructing the scattering coefficient from the optical coherence tomography data. We used this approach to quantify the effective skin dehydration depth and rehydration time in rats ex vivo following the topical application of 70% ethanol and an ethanolic solution of the betamethasone dipropionate glucocorticosteroid, both in the presence and absence of ultrasound exposure (1 MHz, 0.5 W/cm², 2 min). As a result, ethanol was shown to induce reversible dehydration of the upper skin layers (168±88 µm) with the recovery occurring within 21±3 min. Ultrasound treatment of the ethanol application area resulted in the enhancement of its penetration depth up to 262±63 µm and reduced the rehydration time to 14±3 min. The addition of betamethasone dipropionate to the ethanol solution further increased the dehydration depth and delayed rehydration process. Visualization of the obtained data as heatmaps enabled a quantitative evaluation of the spatiotemporal changes in the skin. The proposed approach proved to be effective for investigating water diffusion processes in the skin and would facilitate the analysis of dynamic changes in both healthy and pathological tissues, as well as the assessment of the effects of various topical chemical and physical treatments. This work holds significant implications for both basic and practical research at the interface between optics and biomedicine.

Sequential application of topical medications - applying two or more agents to the same anatomical site - is common in dermatologic practice, particularly for chronic inflammatory conditions requiring combination therapy. Despite its routine use, guidance on application order, timing, and vehicle compatibility remains limited, and the pharmacologic consequences of sequential topical application are not well defined. This review synthesizes current clinical, in vivo volunteer, and mechanistic in vitro/ex vivo evidence evaluating how sequential application influences percutaneous absorption, cutaneous bioavailability, and clinical outcomes. A qualitative literature search identified twelve eligible studies, including randomized controlled trials, in vivo human studies, and mechanistic diffusion and visualization models. Across heterogeneous designs, sequencing was not pharmacologically neutral. Observed effects were driven primarily by barrier state and vehicle/excipient interactions rather than formulation labels alone. Sequencing was most consequential when the first-applied product altered the stratum corneum through keratolysis, hydration or occlusion, or lipid film formation, or when vehicle interactions resulted in redissolution or redistribution of previously applied agents. In barrier-deficient conditions, such as atopic dermatitis, the order of application had less impact on clinical outcomes. Fixed-combination products generally demonstrated more consistent and predictable delivery than free sequential regimens. Collectively, the available evidence supports a mechanism-informed approach to topical sequencing and highlights the need for standardized, clinically relevant studies to guide application order and timing as combination topical therapy continues to expand.

Introduction: Recent progress in supramolecule research has led to a surge in its application in cosmetic products. However, comprehensive investigation of the potential benefits, especially differentiating biological activities and associating that with physical-chemical properties, remains to be established. The current study aimed to investigate the supramolecular salicylic acid-betaine (Supra-SA-B) compared to its physical mixture (SA+B) for effects on epidermal homeostasis and topical insult potential.

Methods: The structure of supra-SA-B and SA+B was characterized by a powder X-ray diffractometer. Skin tolerance was evaluated by applying SA, Supra-SA-B, and SA+B to human keratinocytes or SkinEthic™ reconstructed human epidermis (RHE) models. Inflammatory cytokines were assessed by Luminex assay. Histological morphology was evaluated by hematoxylin-eosin staining, with aquaporin-3 (AQP3) and Ki67 measured by immunofluorescence. RNA sequencing characterized overall biological response.

Results: Characteristic peaks remained the same for Supra-SA-B after freeze-drying verified that their crystalline structures were retained in the current solution. Supra-SA-B treated groups demonstrated significantly higher viabilities compared to SA or SA+B. With 18-h of treatment, Supra-SA-B treated group released fewer cytokines. In addition, Supra-SA-B demonstrated a better hydration effect with increased AQP3 expression and more organized epidermal structure. Consistent result was observed in the RNA transcriptomic profiles of RHE models. Supra-SA-B did not induce major transcriptome drift as compared to SA or SA+B, with less evident negative impact on loricrin, and late cornified envelope gene expression. Hyaluronic acid synthase boosting was maintained.

Conclusion: Supra-SA-B ameliorated skin tolerance risk for SA, enhanced hydration with less insult on barrier functions, suggesting promising potential for cosmetic application.

Introduction: This study investigates the transdermal permeation efficiency and traceability of fluorescent nanodiamond-conjugated small extracellular vesicles (FND-sEVs) derived from umbilical cord mesenchymal stem cells.

Methods: First, the sEVs were isolated and characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis, confirming their typical cup-shaped morphology and size distribution (62.5-141.1 nm) consistent with canonical sEV properties. Subsequently, FNDs were conjugated to sEVs, forming FND-sEVs, whose composite structure - featuring a high-electron-density FND core surrounded by a vesicular sEV membrane - was verified by TEM. Conjugation efficiency was then validated via confocal microscopy, showing complete colocalization between FND fluorescence and Alexa Fluor 488-labeled wheat germ agglutinin-tagged sEVs. Transdermal assessment was conducted using a skin tissue model, with magnetically modulated fluorescence (MMF) spectroscopy applied for background-free quantification.

Results: Leveraging the unique nitrogen-vacancy centers in FNDs (fluorescence lifetime ∼20 ns), MMF eliminated interference from skin autofluorescence (∼3 ns) and enabled direct quantification in tissue digests without pre-separation. FND-sEVs were discovered to remain predominantly in the supernatant, with a measurable fraction permeating skin tissue layers, while their presence in the filtrate was negligible, thereby indicating limited transdermal passage.

Conclusion: Collectively, these findings establish FND-sEVs as a traceable platform for transdermal studies and highlight MMF as a robust tool for quantifying nanoscale vesicle distributions in complex biological matrices.

Introduction: Optical clearing (OC) of biological objects is a promising technique with broad potential in clinical and diagnostic applications, as it enhances imaging depth, spatial resolution, and contrast of acquired images or spectra. The aim of this study was to study the effects of the common optical clearing agents (OCAs) glycerol, fructose, dimethyl sulfoxide (DMSO) and iohexol (Omnipaque®) solutions at various concentrations and treatment durations on the stratum corneum (SC) of intact skin using confocal Raman microspectroscopy (CRM).

Methods: The pig ear was selected for study. Various OCAs were applied topically on the skin, including water solutions of DMSO (100%), fructose (50%), Omnipaque® (90% and 100%), glycerol (40%, 60%, 80%, 90% and 100%). Ex vivo measurements were carried out on porcine ear skin using a Model 3510 SCA confocal Raman microscope (RiverD International B.V., Rotterdam, the Netherlands).

Results: It was found that a 25%-25%-50% water-ethanol-fructose solution permeated the SC at all tested exposure times (5, 15, 30, and 45 min). Similarly, a mixture of 80% glycerol and 20% DMSO, applied for 45 min, also demonstrated effective penetration through the SC. Enhanced OC was achieved by combining OCAs with DMSO, ethanol, or distilled water. The highest OC efficiency was observed with a 25%-25%-50% water-ethanol-fructose solution and a mixture of 90% Omnipaque® with 10% DMSO, both applied for 5 minutes, resulting in a 4.1- and 4.2-fold increase, respectively, in signal intensity at a skin depth of 80 µm. It was shown that the optical properties of the skin can be controlled at a depth of approx. 80 μm. Almost all used OCAs, which are not occlusive from the conventional viewpoint, have an occlusion effect on the SC.

Conclusion: The findings of this study contribute to the identification of optimal OCA combinations - namely, a 25%-25%-50% water-ethanol-fructose solution and a mixture of 90% Omnipaque® with 10% DMSO, each applied for 5 minutes - for potential in vivo applications. Moreover, the results provide a strong foundation for future multimodal investigations aimed at developing advanced methods for visualizing biological tissues and organs and analyzing their biophysical parameters, in conjunction with controlled OC.

Introduction: Heart failure (HF) is an age-related condition that complicates heart disease. Currently, the number of patients with HF continues to increase, representing a significant burden on the healthcare system. Prognostication of patients with HF may be performed with modern spectroscopic approaches.

Methods: This study proposes to utilize conventional spontaneous Raman spectroscopy and autofluorescence for the in vivo analysis of skin tissues to create a prognosis for patients with HF. We collected skin spectral data from 160 HF patients. Twenty-nine patients died during the 1-year observation period. After the preprocessing of spectral data, we proposed a classification model for the prediction of mortality. This model utilizes projection on latent structures combined with discriminant analysis. Stability of the model was demonstrated during division of the data into training and test.

Results: Analysis of full spectral data provided only 55% accuracy in a 1-year mortality prediction, while analysis of autofluorescence and Raman spectral data provides 66% and 70% accuracy, respectively. The combination of autofluorescence and Raman spectroscopy provides an accuracy of 74% (68% sensitivity and 80% specificity) and an receiver operating characteristic-area under the curve of 0.80 for the prediction of 1-year mortality in patients with HF. The most important Raman bands for the prediction of 1-year mortality appeared at 1,086-1,180, 1,320, 1,465, and 1,770 cm-1.

Conclusion: Raman spectroscopy could be a powerful tool for the prognosis of patients with HF; however, further studies on a larger cohort are required to demonstrate the applicability of the proposed spectral in vivo analysis.