Skin Pharmacology and Physiology最新文献

{"title":"A Molecular-Dynamics-Guided Screening Pipeline Identifies Topical Glucocorticoid Receptor Modulators with Selective Epidermal Activation.","authors":"Feng-Chuan Tai, Heng-Hui Lien, Shih-Chang Lin, Yu-Li Hung, Yu-Pin Cheng, Jiun-Wen Guo","doi":"10.1159/000553135","DOIUrl":"10.1159/000553135","url":null,"abstract":"<p><strong>Introduction: </strong>Topical corticosteroids remain the mainstay of psoriasis management but are limited by skin atrophy and barrier impairment. Developing safer, steroid-sparing therapy represents an unmet need in topical pharmacology. The glucocorticoid receptor (GR) plays a central role in epidermal homeostasis, yet selective activation by natural phytochemicals has not been systematically explored.</p><p><strong>Methods: </strong>A molecular modeling framework integrating docking, molecular dynamics simulations, and pharmacophore conservation was established to evaluate GR engagement by four phytochemicals - sakuranetin, salvianolic acid B, lithospermic acid, and magnolol. Computational findings were compared with immunohistochemical analysis of total GR and phosphorylated Ser211-GR in psoriatic epidermal specimens derived from residual archived tissues.</p><p><strong>Results: </strong>Salvianolic acid B and lithospermic acid displayed high docking affinity and stable retention of canonical GR contacts, whereas sakuranetin and magnolol exhibited moderate but consistent binding. Immunohistochemistry confirmed preserved GR abundance for all compounds, with lithospermic acid producing the greatest increase in Ser211 phosphorylation, consistent with differential receptor-associated signaling patterns. Computational and histological findings showed preliminary directional concordance between computational interaction profiles and tissue-level receptor-associated readouts.</p><p><strong>Conclusion: </strong>This study demonstrates that integrating molecular modeling with receptor-associated histological analysis may assist in prioritizing natural compounds with potential GR-engagement properties. The proposed framework provides an exploratory and reproducible strategy for receptor-engagement prioritization in topical pharmacology and may support future investigation of bioactive phytochemicals in dermatologic research.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-21"},"PeriodicalIF":4.1,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional Cutaneous Vasodilatory Responses to Local Heating in Post-Menopausal Females with and without Hormone Replacement Therapy.","authors":"Caroline Li-Maloney, Gregory W McGarr, Sarah J I Johnson, Naoto Fujii, Tatsuro Amano, Glen P Kenny","doi":"10.1159/000552300","DOIUrl":"10.1159/000552300","url":null,"abstract":"<p><strong>Introduction: </strong>We investigated whether post-menopausal females receiving hormone replacement therapy (HRT) exhibit greater nitric oxide (NO)-dependent cutaneous microvascular responses than those not receiving HRT, assessed via pharmacological NO synthase (NOS) inhibition during local heating. We also examined regional differences in microvascular response between and within groups.</p><p><strong>Methods: </strong>Twenty-one post-menopausal females (10 receiving HRT, 11 not receiving HRT) underwent assessment of cutaneous vascular conductance (CVC), expressed as a percentage of maximum vasodilation (%CVC_max), at the chest, abdomen, forearm, and calf using laser-Doppler flowmetry. Local skin temperature was raised from 33°C to 42°C for ∼30 min, followed by ∼40 min perfusion with 20 m<sc>m</sc>NG-nitro-L-arginine methyl ester (L-NAME; NOS inhibitor) using intradermal microdialysis. The NO contribution to vasodilation was defined as the difference in %CVC_max between the 42°C and L-NAME plateau.</p><p><strong>Results: </strong>There were no significant differences in the NO contribution to vasodilation between groups or between sites within groups (all p > 0.107). During baseline, females not receiving HRT demonstrated 7.6 [0.8, 14.4]% higher %CVC_max at the forearm compared with abdomen (p = 0.021). During the 42°C heating plateau, this group also showed abdominal %CVC_max values that were 11.8 [0.04, 23.5]% lower than the calf (p = 0.041) and 12.7 [1.1, 24.4]% lower than the forearm (p = 0.025). Females receiving HRT demonstrated 12.0 [2.4, 21.5]% greater abdominal %CVC_max than those not receiving HRT (p = 0.014).</p><p><strong>Conclusion: </strong>Altogether, our findings indicate that HRT is not associated with NO-dependent cutaneous vasodilation during local heating in post-menopausal females but is associated with regional heterogeneity in cutaneous vasodilatory responses.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-16"},"PeriodicalIF":4.1,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and ex vivo Cutaneous Bioavailability and Biotransformation of Silymarin and Its Constituents.","authors":"Jitka Vostálová, Pavel Kosina, Bohumil Zálešák, Kateřina Valentová, Barbora Papoušková, Alena Ryšavá, Jiří Hanyk, Alena Rajnochová Svobodová","doi":"10.1159/000550859","DOIUrl":"10.1159/000550859","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>Human skin ex vivo (HSE) and normal human dermal fibroblasts (NHDF) were used as experimental models. For cell treatment, a concentration of 10 μmol L-1 (pure compounds) or 4.825 mg L-1 (SM) was used. For HSE treatment, 50 μmol L-1 (pure compounds) or 24.124 mg L-1 (SM) was used.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-20"},"PeriodicalIF":4.1,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optical Coherence Tomography Mapping of the Scattering Coefficient to Study the Skin Hydration Process under Optical Clearing.","authors":"Yury I Surkov, Isabella A Serebryakova, Sergey M Zaytsev, Elina A Genina, Valery V Tuchin, Yulia I Svenskaya","doi":"10.1159/000551016","DOIUrl":"10.1159/000551016","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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, in both the presence and absence of ultrasound exposure (1 MHz, 0.5 W/cm2, 2 min).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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 researches at the interface between optics and biomedicine.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biophysical Alterations of the Stratum Corneum Induced by Optical Clearing Agents: Implications for Efficiency and Safety Optimization.","authors":"Irina Yu Yanina, Maxim E Darvin, Jürgen Lademann, Valery V Tuchin, Johannes Schleusener","doi":"10.1159/000550614","DOIUrl":"10.1159/000550614","url":null,"abstract":"<p><strong>Introduction: </strong>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).</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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 min, 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.</p><p><strong>Conclusion: </strong>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 min - 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.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-21"},"PeriodicalIF":3.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo Raman Spectroscopy of Skin in Predicting Mortality in Patients with Heart Failure.","authors":"Lyudmila A Bratchenko, Yulia A Khristoforova, Maria A Skuratova, Petr A Lebedev, Ivan A Bratchenko","doi":"10.1159/000550638","DOIUrl":"10.1159/000550638","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo Characterization of Colored Tattoo Ink Distribution in Human Skin Using Noninvasive Two-Photon Tomography Combined with Fluorescence Lifetime Imaging Microscopy.","authors":"David A Lopez Guardado, Tatiana B Lepekhina, Stepan D Korkishko, Yury V Kistenev, Viktor V Nikolaev, Maxim E Darvin","doi":"10.1159/000550617","DOIUrl":"10.1159/000550617","url":null,"abstract":"<p><strong>Introduction: </strong>In recent years, multicolored tattoos have gained popularity among young individuals. However, the behavior of tattoo inks in the skin, including their distribution, accumulation, and long-term effects, remains poorly understood, partly due to limited in vivo imaging techniques.</p><p><strong>Methods: </strong>This study employs picosecond-pulsed two-photon excited fluorescence lifetime imaging microscopy (TPE-FLIM) to noninvasively visualize the deposition of colored tattoo ink pigments (blue, red, green, yellow, orange, purple, and black) in human skin in vivo at depths of up to ≈150 µm.</p><p><strong>Results: </strong>The study reveals that tattoo ink agglomerates are present across various skin layers, ranging from the stratum corneum to the reticular dermis. Tattoo ink pigments were predominantly observed within dermal cells, including mast cells, macrophages, and fibroblasts, suggesting that these cells act as long-term reservoirs for the pigments. Additionally, ink residues were detected in epidermal cells, including keratinocytes, dendritic cells, and basal cells, indicating a continuous low-level release of the ink even in old tattoos. Furthermore, the analysis showed that melanin can be distinguished from certain tattoo ink pigments using phasor approach combined with TPE autofluorescence imaging.</p><p><strong>Conclusion: </strong>The TPE-FLIM technique enables in vivo visualization of epidermal dendritic cells and dermal fibroblasts, which are otherwise undetectable using conventional optical methods without staining. This method holds significant potential for clinical dermatology by offering insights into cellular uptake, accumulation, and long-term effects of tattoo inks, thereby supporting the management of tattoo-related complications.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated Segmentation and Skin-Layer Thickness Estimation by Extracting the Optical Scattering Coefficient and Speckle Contrast Parameter from Optical Coherence Tomography Scans.","authors":"Alexander A Sovetsky, Ksenia S Petrova, Maria A Brueva, Maxim G Ryabkov, Alexander L Matveyev, Lev A Matveev, Vladimir Y Zaitsev","doi":"10.1159/000550613","DOIUrl":"10.1159/000550613","url":null,"abstract":"<p><strong>Introduction: </strong>Knowing thicknesses of skin-tissue layers within the depths of several hundred micrometers from the surface is highly important for numerous biomedical applications - cosmetology, treatment of wounds and burns, characterization of various lesions, etc. In this regard, optical coherence tomography (OCT) with its ability to noninvasively enable visualization depth of the order of 1 mm with a resolution of the order of several micrometers offers exceptional diagnostic possibilities largely unavailable to other techniques. This explains high interest to OCT utilization in dermatology.</p><p><strong>Methods: </strong>This study demonstrates that appropriate physics-based processing of OCT data allows one to objectively reveal and automatically estimate thicknesses of morphological skin layers, even if they are not visible as optical layers with differing intensity in initial structural OCT scans. To this end, we apply recently developed efficient methods of spatially resolved estimation of the scattering coefficient µ_s to locally characterize the scattering strength of scatterers in the tissue. Another useful parameter termed speckle contrast (SC_I) characterizes fluctuations of scattering strengths of scatterers and their clustering. Mapping parameters µ_s and SC_I enable differentiation of morphological skin layers, although in structural OCT scans they cannot be clearly delineated even by experts.</p><p><strong>Results: </strong>Analysis of parameters µs and SC_I for OCT data in vivo acquired in various localizations for women and man of various ages confirmed the possibility to clearly segment three medically significant skin layers: (i) stratum corneum, (ii) living-cell layer of epidermis, and (iii) upper dermis layer even if in the initial OCT scans these layers are hardly discernible. The present study is intentionally limited to healthy facial skin, for which significant variations in the layer thicknesses were demonstrated for various age groups, as well as in quite close localizations for the same person.</p><p><strong>Conclusion: </strong>These findings underscore high potential of in vivo OCT imaging supplemented with the analysis of speckle features and optical attenuation parameter for objective real-time differentiation of morphological skin layers, which is critically important for numerous applications (surgical reconstruction of skin wounds and/or burn injuries, controlled drug delivery in targeted skin layers, choice of therapy). Similar approach may be extended for diagnosing various skin diseases/pathologies.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-21"},"PeriodicalIF":3.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Approach for Assessment of Dermal Absorption of Extracellular Vesicle Products Using Immunoaffinity Fluorescent Nanodiamonds.","authors":"Meng-Chien Willie Hsieh, Yung-Shun Su, Liang-Yu Chen, Zhi-Xuan Zhang, Long-Jyun Su, Hsin-Hung Lin, Yi-Chia Wu","doi":"10.1159/000550612","DOIUrl":"10.1159/000550612","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"35-46"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Glyceryl Ascorbate Derivatives Inhibit Type 2 Alarmin Cytokine Induction and Promote Expression of Epidermal Barrier Function-Related Factors in Human Keratinocytes in vitro.","authors":"Shunya Sahara, Natsuki Wakita, Miki Iwai, Ayumi Ueno, Miki Kuribayashi, Koich Nakaoji, Kazuhiko Hamada, Manabu Fujimoto","doi":"10.1159/000551909","DOIUrl":"10.1159/000551909","url":null,"abstract":"<p><strong>Introduction: </strong>Atopic dermatitis is characterized by the interplay among type 2 immune responses, skin barrier dysfunction, and pruritus. Despite the pivotal role of interleukin-33 in the pathogenesis of the disease, novel therapeutic strategies remain limited.</p><p><strong>Methods: </strong>In this study, we investigated the effects of 2-O-glyceryl-6-O-hexadecanoyl ascorbic acid (2GA16), assessing its impact on inflammatory cytokine production in an epidermal cell-based atopic dermatitis model. Specifically, 2GA16 was introduced to cultured keratinocytes in an inflammatory state induced by phorbol-12-myristate-13-acetate. The inhibitory effects on inflammatory cytokines were confirmed through gene expression analysis.</p><p><strong>Results: </strong>The analysis revealed that 2GA16 suppressed the increased expression levels of alarmins, particularly interleukin-33, in a dose-dependent manner (p < 0.01). Epidermal cells treated with 2GA16 exhibited increased expression levels of filaggrin and involucrin, both crucial to epidermal barrier formation (p < 0.05). Such changes were further supported by Western blot analysis and ex vivo tissue staining, which qualitatively showed corresponding changes at the protein level.</p><p><strong>Conclusion: </strong>These findings suggest that 2GA16 may mitigate the symptoms of atopic dermatitis by inhibiting the induction of type 2 alarmin cytokines in keratinocytes and restoring their capacity to form effective epidermal barriers.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"185-196"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}