Skin Pharmacology and Physiology最新文献

{"title":"Imaging Active Drug Transport in Viable Human Skin: A Functional ex vivo Skin Model for Mechanistic and Regulatory Applications.","authors":"Krishna Chaitanya Telaprolu, Jonathan Wei, Jeffrey E Grice, Yousuf Mohammed, Michael S Roberts","doi":"10.1159/spp/aetag009","DOIUrl":"10.1159/spp/aetag009","url":null,"abstract":"<p><strong>Introduction: </strong>Understanding drug diffusion and active transport in the viable epidermis (VE) is critical for optimizing topical and transdermal drug delivery. However, the VE remains understudied due to challenges in isolating physiologically intact membranes and limited functional data on cutaneous transporters. This study aimed to develop and validate a viable human epidermal model to assess molecular diffusion and transporter activity using high-resolution imaging, with a focus on P-glycoprotein (P-gp)-mediated transport.</p><p><strong>Methods: </strong>Viable epidermis was enzymatically separated from dermatomed human skin using dispase II. Tissue viability was confirmed by MPT-FLIM, MTT assay, and H&E staining. Multiphoton microscopy (MPM) was employed to visualize the diffusion of rhodamine 123 (RD123), a fluorescent P-gp substrate, in dispase-separated epidermis (DSE), and heat-separated epidermis (HSE). The influence of P-gp was evaluated by pretreatment with verapamil, a known inhibitor. ImageJ and MATLAB were used for quantitative image analysis.</p><p><strong>Results: </strong>RD123 diffusion was faster and more extensive in verapamil-treated DSE, with increased fluorescence intensity in the basal and suprabasal layers at early time points compared to controls. HSE exhibited significantly reduced fluorescence and compromised cellular architecture. MPT-FLIM analysis confirmed that the average NAD(P)H fluorescence lifetime and a₁/a₂ metabolic ratios in DSE were comparable to control DTM, indicating preservation of metabolic activity.</p><p><strong>Conclusion: </strong>This study establishes a viable, structurally intact epidermal model suitable for evaluating both passive and active transport in human skin. Functional imaging confirmed the role of P-gp in modulating drug diffusion across the VE. This platform supports the generation of mechanistic data for improving dermal pharmacokinetic models and has translational relevance for formulation design and regulatory assessment of topical therapies.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064354","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":"Evaluation of Hyaluronic Acid-Based Microneedle Patches for Anti-Wrinkle Effects and Skin Quality Improvement: A Prospective, Open-Label and Interventional Preliminary Study.","authors":"Katarzyna Jacyszyn, Aleksandra Kuzan, Miroslaw Sopel","doi":"10.1159/spp/aetag012","DOIUrl":"https://doi.org/10.1159/spp/aetag012","url":null,"abstract":"<p><strong>Introduction: </strong>Hyaluronic acid (HA) is a widely utilized polysaccharide in dermatology due to its excellent biocompatibility and hydrating properties. Traditional delivery methods of HA include injections and topical applications; however, their effectiveness is limited due to skin permeability barriers. Microneedle technology offers a novel transdermal delivery system that enhances HA penetration while minimizing discomfort. This study investigates the application of dissolvable HA based multicomponent microneedle patches for anti-wrinkle treatment and overall skin improvement.</p><p><strong>Methods: </strong>The study involved 40 participants, aged 22-43. The microneedle patches were composed of cross-linked HA, applied under the eye and on the arm, for three consecutive nights. Their morphology and dissolution, properties were assessed using scanning electron microscopy and dissolution testing in controlled humidity environments. Skin hydration was measured using a corneometer, elasticity with a reviscometer, and wrinkle depth with a 3D skin analysis system. Participants rated their perceived improvement using the Global Aesthetic Improvement Scale.</p><p><strong>Results: </strong>SEM analysis revealed uniform microneedle structures with an average length of 310 µm. The microneedle patches gradually dissolved within 240 minutes of application, with the first morphological changes visible after just 20 minutes. Corneometer measurements showed an increase in skin hydration by about 10%, accompanied by improved smoothing parameters (profilometry). Reviscometer measurements demonstrated an increase in resonance running time at the treated forearm (+11.7%), indicating changes in the mechanical properties of the skin. GAIS scores reflected high participant satisfaction, with 82% of subjects reporting visible skin improvement. Mild erythema was observed in 3% of participants, resolving within a few hours post-application. No severe adverse effects were reported. While these findings suggest that HA-based microneedle patches improve hydration andenhances skin smoothness, the accompanying ∼17% transient increase in TEWL necessitates a cautious interpretation of these short-term skin quality improvements.</p><p><strong>Conclusion: </strong>HA based multicomponent microneedle patches may be a promising, non-invasive method for improving skin appearance, however, the observed transient increase in TEWL indicates that the effects should be interpreted with caution and require confirmation in studies with longer follow-up. Their ability to enhance hydration, elasticity, and smoothing the skinwith minimal side effects highlights their potential for widespread dermatological and aesthetic use.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002441","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":"Sebocyte Dysfunction in Skin Health and Disease: Physiological Regulation, Pharmacological Modulation, and Therapeutic Targeting.","authors":"Maryam Adelipour, Jeongkwon Kim","doi":"10.1159/spp/aetag010","DOIUrl":"https://doi.org/10.1159/spp/aetag010","url":null,"abstract":"<p><strong>Background: </strong>Sebaceous glands and their specialized lipid-producing cells, sebocytes, are essential for maintaining skin homeostasis through sebum production, barrier support, and immune regulation. Dysregulated sebocyte activity contributes to common inflammatory skin disorders, particularly acne vulgaris and seborrheic dermatitis. Although many studies have examined individual regulators of sebocyte function, current knowledge remains fragmented across metabolic, hormonal, inflammatory, microbial, and environmental pathways.</p><p><strong>Summary: </strong>This review provides a pathway-centered overview of sebocyte biology, with emphasis on the physiological and pharmacological mechanisms that regulate lipid metabolism, differentiation, proliferation, and inflammatory responses. Intrinsic signals, including androgens, insulin-like growth factor 1, epidermal growth factor, vitamin D, and stress-related mediators, interact with extrinsic factors such as microbial stimuli, hypoxia, radiation, and chemical exposures. These diverse inputs converge on recurrent regulatory hubs, including PI3K/Akt/mTOR, AMPK/SIRT1, TLR/NF-κB, AhR, and inflammasome-associated pathways. This review further discusses how therapeutic agents and bioactive compounds modulate these networks through shared control points that coordinate sebogenesis, inflammation, and sebocyte differentiation. Although sebocyte-based models provide valuable mechanistic insight into pathway-level regulation, further validation in physiologically complex and clinically relevant systems remains important.</p><p><strong>Key messages: </strong>Sebocytes should be viewed not only as lipid-producing cells but also as immunometabolic regulators of the skin microenvironment. A pathway-centric framework helps connect diverse upstream stimuli with a limited number of disease-relevant functional outcomes. Targeting shared regulatory hubs, rather than single downstream effectors, may provide a more rational basis for developing therapeutic strategies for sebaceous gland-associated disorders.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930926","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":"Comparison of Dermatoscopic features between acne vulgaris, acneiform rash and exanthematous pustulosis induced by antitumor therapy: A proposed diagnostic algorithm.","authors":"Anastasiia Allenova, Andrey Lvov, Larisa Kruglova, Daria Vorobeva, Daria Shushkanova, Anna Michenko","doi":"10.1159/spp/aetag007","DOIUrl":"https://doi.org/10.1159/spp/aetag007","url":null,"abstract":"<p><p>Background Studies devoted to the assessment of dermatoscopic signs in patients with acneiform rashes and acute exanthematous pustulosis induced by antitumor therapy, as well as acne vulgaris are few and do not evaluate differential diagnostic criteria. There are currently no dermatoscopic algorithms available for the differentiation of these conditions. Aim: To assess the dermatoscopic features specific to acneiform rashes in comparison with acne vulgaris and acute exanthematous pustulosis and to develop an algorithm for differential diagnosis. Methods A multicenter, cross-sectional, observational, prospective study was conducted. Adult patients with acneiform rashes associated with antitumor therapy, acne vulgaris, and acute exanthematous pustulosis were included. Dermatoscopic signs were described according to the recommendations of the International Dermoscopy Society for describing of inflammatory dermatoses. Results Acne vulgaris was characterized by brown-yellow clods on skin-colored areas, white-yellow structureless zones with thin branching vessels, pink structureless zones, white clods surrounded by erythema, white structureless zones (p < 0.001), structureless red-brown zones (p = 0.02), and pink follicular fluorescence in UV light. Acneiform rashes demonstrated erythema with telangiectasia (p = 0.02), purpura (p = 0.001), yellow clods surrounded by erythema, a keratin plug in the center of the pustule, purpura, hemorrhagic spots, keratosis follicularis, yellow crusts, pustules surrounded by erythema with telangiectasia, white scales, and under UV dermatoscopy, keratosis follicularis was observed as white follicular fluorescence (p < 0.001). Acute exanthematous pustulosis showed white clods on structureless erythema without specific fluorescence under UV light, although white clods disappeared under UV light. A Venn diagram was used to develop an algorithm for the differential diagnosis of these three disorders. Conclusion Based on a detailed study of dermatoscopic signs and their analysis using Venn diagrams, we developed an algorithm for the differential diagnosis of acneiform rashes, acute exanthematous pustulosis caused by antitumor therapy, and acne vulgaris. The proposed algorithm may be recommended for clinical use.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913317","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":"Systemic Interventions Targeting Epidermal Barrier Function: Translational Insights from Oral Probiotics.","authors":"Li-Ching Chen, Yung-Chuan Chen, Pei-Wen Sun, Yu-Ping Cheng, Shih-Chang Lin, Jiun-Wen Guo","doi":"10.1159/spp/aetag003","DOIUrl":"10.1159/spp/aetag003","url":null,"abstract":"<p><strong>Background: </strong>The epidermal barrier is increasingly recognized as a dynamic and pharmacologically targetable system that extends beyond its traditional role as a passive structural defense. In inflammatory skin diseases such as atopic dermatitis and psoriasis, barrier dysfunction contributes not only to increased permeability and environmental susceptibility but also to complex bidirectional interactions involving immune dysregulation, microbial imbalance, oxidative stress, and systemic inflammation. Emerging evidence further supports the concept of the gut-skin axis as a systemic regulatory network linking intestinal microbiota, microbial metabolites, immune signaling, and epidermal homeostasis.</p><p><strong>Summary: </strong>Microbiota-derived metabolites, including short-chain fatty acids and aryl hydrocarbon receptor-related microbial metabolites, have been implicated in the regulation of keratinocyte differentiation, lipid metabolism, and epithelial integrity. Within this framework, oral probiotics have attracted increasing attention as biologically plausible systemic modulators of skin barrier function. Experimental and translational studies suggest that probiotics may improve transepidermal water loss, barrier-associated protein expression, inflammatory signaling, and microbial homeostasis through immune and metabolic mechanisms. However, current evidence remains heterogeneous because of strain-specific variability, inconsistent study methodologies, and limited standardized barrier-associated endpoints. Consequently, the clinical utility of microbiome-targeted therapy remains substantially stronger at the mechanistic and preclinical level than at the level of standardized large-scale clinical validation. Current evidence is also considerably more developed in atopic dermatitis than in psoriasis and other inflammatory dermatoses.</p><p><strong>Key messages: </strong>Future progress in microbiome-targeted barrier therapy will likely depend on integrated multi-omics analyses, functional barrier phenotyping, host-genetic stratification, and longitudinal therapeutic monitoring to enable precision barrier-centered interventions and personalized dermatologic strategies.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797853","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":"Daily Photoprotection Mitigates Seasonal Skin Changes and Supports Skin Longevity: A 1-Year in vivo 3D Multiphoton Microscopy Study.","authors":"Edouard Raynaud, Barbara Lynch, Blandine Ngo, Géraldine Rolland, Steeve Victorin, Olivia Dufour, Thomas Bornschlögl, Angelina Roudot, Mahassine Safouane, Luc Aguilar, Sébastien Brizion, Thérèse Baldeweck, Ana-Maria Pena","doi":"10.1159/spp/aetag002","DOIUrl":"10.1159/spp/aetag002","url":null,"abstract":"<p><strong>Introduction: </strong>While the detrimental effects of intense sun exposure are well-recognized, the cumulative impact of daily moderate UV exposure remains less explored. This year-long study investigated the effects of seasonal variations on facial skin, aiming at highlighting subclinical skin changes using non-invasive in vivo multiphoton microscopy. We also explored the impact of applying daily a well-balanced photoprotection formula with enhanced UVA filtration.</p><p><strong>Methods: </strong>Fifty-nine European descent women (aged 55-65, Fitzpatrick phototypes II or III), participated in this year long, real-life exposure study in Paris, France. Participants were randomized into two double-blind groups: one applying a daily broad-spectrum sun protection factor (SPF) /persistent pigment darkening (PPD) photoprotection product, the other applying the vehicle. In vivo assessments were conducted at four seasonal time points to measure the skin color and multiphoton parameters: melanin density and z-epidermal distribution, epidermal morphology, elastin, and fibrillar collagen densities in the papillary dermis (first 20 µm-thick dermal sublayer below the dermal-epidermal junction) and their combined 3D SAAID aging index, a marker of photoaging.</p><p><strong>Results: </strong>The vehicle group exhibited a significant increase in skin color, melanin density, elastin density and a decrease in the 3D-SAAID aging index between winter and summer, reflecting seasonal UV impact. These changes were not observed in the photoprotected group.</p><p><strong>Conclusion: </strong>This study provides in vivo evidence that real-life sun exposure, even under moderate conditions, can induce subclinical skin changes. Daily use of sunscreen with enhanced UVA protection mitigated these effects, highlighting the importance of consistent photoprotection in preventing long-term UV-induced clinical aging signs and supporting skin longevity.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707409","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":"Ceramides and the Defective Barrier in Atopic Dermatitis.","authors":"Philip W Wertz, Joachim W Fluhr","doi":"10.1159/spp/aetag001","DOIUrl":"10.1159/spp/aetag001","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a common remitting-relapsing inflammatory skin disease characterized by eczematous lesions, xerosis, and pruritus. It is associated with a defective permeability barrier and increased susceptibility to Staphylococcus aureus colonization. It has been demonstrated that the abrogated epidermal barrier is related to a decreased mass of ceramides and long-chain fatty acids in the stratum corneum (SC). The inherent pH of healthy SC is below 5, and a low pH is required for proper assembly of the barrier lipids. In AD, the pH is elevated.</p><p><strong>Summary: </strong>A defective permeability barrier of the SC is the primary defect in AD. This defect reflects a reduction of ceramide and fatty acid mass in the SC due to reduced glucocerebrosidase and acid sphingomyelinase activity and a shift in fatty acid synthesis from long-chain to short-chain fatty acids and the incorporation of these shorter fatty acids into ceramides. Topically applied ceramides can restore epidermal function to a damaged barrier. Ceramide-containing moisturizers have produced partial restoration of the barrier function in AD by influencing lipid organization. Other topical and systemic therapies are also discussed.</p><p><strong>Key message: </strong>Correcting the barrier defect by topically supplied ceramides and long-chain fatty acids in sufficient amounts could contribute to restoration of the microbiome and decreasing irritation and pruritus.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621037","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":"Methods to Detect Antioxidants and Free Radicals in Human Skin and Its Applications with Focus on Asian Skin.","authors":"Li Chen, Alexandra Lan, Yifan He, Chenxi Bao, Wenting Hu, Shuyun Xi, Leonhard Zastrow, Silke B Lohan, Martina C Meinke, Jürgen Lademann","doi":"10.1159/000553330","DOIUrl":"10.1159/000553330","url":null,"abstract":"<p><strong>Background: </strong>The interaction between antioxidants and free radicals has become increasingly important in cosmetic research. This review is not a conventional literature overview but is primarily based on our own experimental data and methodological developments.</p><p><strong>Summary: </strong>The first part describes noninvasive spectroscopic techniques, such as resonance Raman spectroscopy are highlighted as robust tools for the in vivo determination of carotenoid concentrations, serving as indirect markers of the skin's antioxidant status. The next section addresses the detection of free radicals. Electron paramagnetic resonance (EPR) spectroscopy is presented as the only direct and quantitative method for detecting free radicals in biological systems. Its application in vitro, ex vivo, and in vivo enables controlled assessment of radical formation and antioxidant efficacy, including under defined irradiation conditions. The introduction of the radical protection factor (RPF) provides a standardized parameter to compare the scavenging capacity of individual compounds and complex formulations, thereby supporting product development and claim substantiation. In the last section, in vivo and ex vivo measurements are compared. It is shown that the amounts of free radicals generated in the UV and infrared spectral ranges of solar radiation differ significantly between different skin types. For sun protection, this means that the protective effect of a sunscreen must extend across the entire spectral range of solar radiation, since 50% of the free radicals generated by the sun originate in the visible and infrared spectral ranges.</p><p><strong>Key messages: </strong>These findings led to the development of a sunscreen important for Asian skin (skin type IV).</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-12"},"PeriodicalIF":4.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369673","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":"Multiphoton Tomography of Micro- and Nanocosmetics in Human Skin: In vivo Studies in Volunteers and Patients with ex vivo Validation.","authors":"Ana Carolina Henriques Ribeiro Machado, Yousuf Mohammed, Michael S Roberts, Vania Rodrigues Leite-Silva","doi":"10.1159/000553032","DOIUrl":"10.1159/000553032","url":null,"abstract":"<p><strong>Background: </strong>A holy grail in human skin permeation is to be able to quantify how compounds and nanoparticles are absorbed, distributed, and exert their effects. Traditionally, the processes used have either been destructive or relied upon interpreting what has exited the skin after absorption, be it in in vivo plasma or urine or through ex vivo skin. Multiphoton imaging and other modalities have revolutionized this landscape.</p><p><strong>Summary: </strong>In this review article, we summarize our experiences in using multiphoton tomography and fluorescence lifetime imaging in characterizing the skin absorption, distribution, and redox effects of nanoparticulate and related delivery systems. Much of our work has been focused on the absorption and safety of nano zinc oxide which started off being an apparently unsafe product to now being an FDA GRAS substance. We have found that the skin is a remarkable physical barrier to zinc oxide nanoparticles, as well as to other nanoparticles, under a wide range of formulation and method of use conditions. However, this work has only been made possible for us by the development of confocal, multiphoton, and fluorescence lifetime imaging technologies that can be safely used on human skin.</p><p><strong>Key messages: </strong>(1) Multiphoton tomography and fluorescence lifetime imaging have allowed us, for the first time, to safely image the transport of compounds and structures in human skin in vivo and to assess the redox state of the skin after that application. (2) A key use of this instrumentation and related techniques has been to show that the sunscreen, nano zinc oxide, is generally safe when applied to human skin in various formulations and under a wide range of conditions. (3) We have also shown that characterizing nano-zinc oxide skin absorption by urinary zinc isotope excretion is misleading because, in our experience, zinc oxide nanoparticles are hydrolyzed to zinc ions which are readily absorbed into the viable epidermis and will be excreted in the urine. (4) We have also shown other nanoparticles, such as quantum dots, silver, and gold, are poorly absorbed into the skin. (5) However, our imaging does show that nanoparticles can accumulate and be difficult to wash out of skin furrows and hair follicles, creating a reservoir effect. (6) While this review has emphasized studies exploring the safety of topical ZnO-NP and related materials, we have also shown that multiphoton tomography and related techniques may be used in the quality, therapeutic, and theranostic assessment of topical products.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-15"},"PeriodicalIF":4.1,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148332937","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":"Simulated Microgravity Suppresses Proline Biosynthesis in Skin Fibroblasts to Impair Skin Structure.","authors":"Wenbin Wang, Xiufen Peng, Qing Luo, Guanbin Song","doi":"10.1159/000553136","DOIUrl":"10.1159/000553136","url":null,"abstract":"<p><strong>Introduction: </strong>Microgravity during spaceflight is increasingly associated with cutaneous impairment, yet the structural basis and underlying metabolic mechanisms remain poorly defined. Collagen, the main component of the dermal extracellular matrix, relies on de novo proline synthesis in fibroblasts. Herein, we examined whether simulated microgravity (SMG) affects collagen synthesis by altering the proline biosynthetic pathway.</p><p><strong>Methods: </strong>SMG was established using a hindlimb unloading model in rats and a rotating flat chamber system in skin fibroblasts. Dermal morphology and collagen deposition were assessed in skin tissue, while collagen synthesis, intracellular proline levels, and pyrroline-5-carboxylate reductase 1 (PYCR1) expression were examined in fibroblasts. PYCR1 was overexpressed to evaluate its contribution to proline synthesis under SMG.</p><p><strong>Results: </strong>SMG caused dermal thinning and reduced collagen deposition in rat skin, and it similarly decreased collagen production in fibroblasts. SMG also lowered intracellular proline levels in fibroblasts and downregulated the PYCR1 gene. Importantly, PYCR1 overexpression partially restored intracellular proline levels and restored collagen protein expression under SMG conditions.</p><p><strong>Conclusion: </strong>These findings indicate that impaired de novo proline biosynthesis, associated with PYCR1 downregulation, contributes to reduced collagen production and may underlie microgravity-induced dermal structural alterations.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-8"},"PeriodicalIF":4.1,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148332954","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}