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9 pages, 712 KB  
Article
Cutaneous Melanoma and Occupational UV Exposure: Associations with Anatomical Site, Histological Subtype, and Breslow Thickness
by Vincenzo De Giorgi, Silvia Viscera, Giovanni Cecchi, Elisabetta Magnaterra, Veronica Traversini, Gabriella Perillo, Biancamaria Zuccaro, Federica Fazzari, Antonio Baldassarre, Stefano Dugheri and Nicola Mucci
Cancers 2025, 17(16), 2705; https://doi.org/10.3390/cancers17162705 - 20 Aug 2025
Viewed by 461
Abstract
Background: The relationship between occupational sun exposure and melanoma risk is complex and multifaceted, with existing evidence yielding contradictory findings. Unlike Non-Melanoma Skin Cancer (NMSC), for which occupational sun exposure is a well-established risk factor, the link with cutaneous melanoma remains contentious. Objectives: [...] Read more.
Background: The relationship between occupational sun exposure and melanoma risk is complex and multifaceted, with existing evidence yielding contradictory findings. Unlike Non-Melanoma Skin Cancer (NMSC), for which occupational sun exposure is a well-established risk factor, the link with cutaneous melanoma remains contentious. Objectives: This study aimed to evaluate whether, in a cohort of patients with cutaneous melanoma, an association existed between occupational sun exposure and melanoma, specifically with histotype, site of occurrence, and Breslow index. Methods: This is a retrospective cohort analysis conducted to evaluate whether occupational sun exposure constitutes a risk factor for the development of cutaneous melanoma in patients diagnosed between January 2005 and October 2023 at the Dermatology Unit, Azienda USL Toscana Centro, Florence. Occupational ultraviolet (UV) exposure was examined by classifying each participant’s job into categories based on solar UV exposure levels—outdoor (e.g., agriculture and construction roles), mixed indoor/outdoor (e.g., trades and public safety professions), and indoor settings (e.g., office-based work). Results: A final total of 1417 patients were analyzed. Occupational categorization revealed that 1171 patients (82.64%) were classified as non-occupationally exposed (indoor), while 246 (17.36%) were occupationally exposed to solar UV radiation (including 14.82% mixed indoor/outdoor and 2.54% outdoor workers). A significant association was observed between occupational sun exposure and lentigo maligna, which was more prevalent among exposed workers and even more so in the outdoor subgroup. Anatomical site distribution exhibited a significant association with occupational sun exposure. Indeed occupationally exposed individuals showed a higher prevalence of melanomas in the head and neck region, a distribution pattern particularly evident among outdoor workers, suggesting that these sites may be more susceptible to chronic sun exposure in outdoor and mixed occupations. Moreover, a significant association was found between occupational exposure and Breslow thickness, with exposed workers presenting with thicker melanomas at diagnosis, suggesting more advanced disease. Conclusions: The finding of this study may reflect variations in occupational sun exposure patterns and warrants further investigation into protective measures and early-detection strategies tailored to occupational groups. Full article
(This article belongs to the Section Clinical Research of Cancer)
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12 pages, 923 KB  
Article
Effect of Ultraviolet Light on the Shear Bond Strength of Commercial Dental Adhesives
by Markus Heyder, Stefan Kranz, Johanna Sandra Woelfel, Tabea Raabe, André Guellmar, Anna Mrozinska, Michael Gottschaldt, Ulrich S. Schubert, Bernd W. Sigusch and Markus Reise
Materials 2025, 18(16), 3772; https://doi.org/10.3390/ma18163772 - 12 Aug 2025
Viewed by 313
Abstract
Background: In adhesive dentistry, debonding-on-demand is attractive for situations where no permanent attachment is required. Due to its destructive nature, ultraviolet (UV) light may be of interest for attenuating bond forces. The aim of this study was to investigate the impact of UV [...] Read more.
Background: In adhesive dentistry, debonding-on-demand is attractive for situations where no permanent attachment is required. Due to its destructive nature, ultraviolet (UV) light may be of interest for attenuating bond forces. The aim of this study was to investigate the impact of UV light on the shear bond strength (SBS) of etch-and-rinse (n = 4) and universal adhesives (n = 3). Methods: Glass-ceramic samples were bonded to bovine enamel surfaces (n = 10/adhesive) and subjected to shear bond testing before and after exposure to UV light (320–390 nm, 126 Jcm−2). Data was statistically analyzed by Mann–Whitney U test. Results: Initial photopolymerized etch-and-rinse adhesives showed superior SBS compared to universal adhesives. Highest values were recorded for iBOND® Total etch (15.48 MPa) and Syntac classic© (17.60 MPa). Lowest SBS was obtained for Ecosite Bond® (2.63 MPa). Additional UV exposure caused a significant decrease in SBS among iBOND Total etch (5.24 MPa, p = 0.009) and Solobond M© (3.65 MPa, p = 0.005), while for Syntac classic©, an increase (24.12 MPa, p = 0.047) was recorded. Among all other tested adhesives, no significant changes were observed. Conclusions: UV radiation impacted SBS of etch-and-rinse adhesives only (decrease: iBOND Total Etch, Solobond M; enhancement: Syntac classic©). Further research should focus on introducing sufficient light-triggered debonding mechanisms. Full article
(This article belongs to the Section Biomaterials)
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19 pages, 4295 KB  
Article
Genistein and Curcumin Inhibit Proliferation and Invasiveness in BRAFV600E Mutant and Wild-Type Melanoma Cells: Insights into Their Anticancer Effects
by Federico Vaccaro, Federica Mannino, Mariacarmela Santarpia, Chiara Cullotta, Mariarosaria Galeano, Francesco Borgia, Federica Li Pomi, Vincenzo Arcoraci, Maria Lentini, Mariausilia Franchina, Mario Vaccaro, Giovanni Pallio and Natasha Irrera
Biomedicines 2025, 13(8), 1954; https://doi.org/10.3390/biomedicines13081954 - 10 Aug 2025
Viewed by 480
Abstract
Background/objectives: Melanoma is one of the deadliest forms of malignant cancers; ultraviolet radiation exposure together with genetic mutations, such as BRAF, represent the main risk factors and are involved in metastatic dissemination. Previous studies demonstrated the anti-emetic and anti-proliferative effects of the [...] Read more.
Background/objectives: Melanoma is one of the deadliest forms of malignant cancers; ultraviolet radiation exposure together with genetic mutations, such as BRAF, represent the main risk factors and are involved in metastatic dissemination. Previous studies demonstrated the anti-emetic and anti-proliferative effects of the flavonoid genistein and the turmeric curcumin in cancers. This study aimed at investigating the anticancer effects of curcumin, genistein and their association in melanoma cells. Methods: Human A375 and CHL-1 cell lines were cultured and treated with different concentrations of curcumin or genistein or curcumin + genistein for 24 h according to IC50. Results: Genistein and curcumin induced cell death, as demonstrated by MTT assay and FDA/PI staining. The anti-apoptotic protein Bcl-2 was significantly reduced after curcumin and curcumin + genistein treatment, but unexpectedly not with genistein alone. Curcumin and genistein significantly increased DNA fragmentation, thus indicating apoptosis induction. Moreover, comet assay confirmed that curcumin and genistein stimulated cell death, as quantified by measuring the displacement between the ‘comet head’ and the resulting ‘tail’. FAK protein expression was significantly reduced by genistein and curcumin in CHL-1 cells and after the treatment with genistein + curcumin in the most aggressive A375 cells. These anti-proliferative effects were confirmed by scratch assay and phospho-p38 reduction. Moreover, both curcumin and genistein alone and in association inhibited cell adhesion, thus indicating that these nutraceuticals could reduce invasion and metastasis. Conclusion: The obtained results provided new insights for the anticancer effects of genistein and curcumin, which could be used to improve therapeutic adherence and drug response. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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21 pages, 3048 KB  
Article
Transfersome-Based Delivery of Optimized Black Tea Extract for the Prevention of UVB-Induced Skin Damage
by Nadia Benedetto, Maria Ponticelli, Ludovica Lela, Emanuele Rosa, Flavia Carriero, Immacolata Faraone, Carla Caddeo, Luigi Milella and Antonio Vassallo
Pharmaceutics 2025, 17(8), 952; https://doi.org/10.3390/pharmaceutics17080952 - 23 Jul 2025
Viewed by 461
Abstract
Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize [...] Read more.
Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize the extraction of theaflavins and thearubigins from black tea leaves and evaluate the efficacy of the extract against UVB-induced damage using a transfersome-based topical formulation. Methods: Extraction of theaflavins and thearubigins was optimized via response surface methodology (Box-Behnken Design), yielding an extract rich in active polyphenols. This extract was incorporated into transfersomes that were characterized for size, polydispersity, zeta potential, storage stability, and entrapment efficiency. Human dermal fibroblasts (NHDF) were used to assess cytotoxicity, protection against UVB-induced viability loss, collagen degradation, and expression of inflammatory (IL6, COX2, iNOS) and matrix-degrading (MMP1) markers. Cellular uptake of the extract’s bioactive marker compounds was measured via LC-MS/MS. Results: The transfersomes (~60 nm) showed a good stability and a high entrapment efficiency (>85%). The transfersomes significantly protected NHDF cells from UVB-induced cytotoxicity, restored collagen production, and reduced gene expression of MMP1, IL6, COX2, and iNOS. Cellular uptake of key extract’s polyphenols was markedly enhanced by the nanoformulation compared to the free extract. Conclusions: Black tea extract transfersomes effectively prevented UVB-induced oxidative and inflammatory damage in skin fibroblasts. This delivery system enhanced bioavailability of the extract and cellular protection, supporting the use of the optimized extract in cosmeceutical formulations targeting photoaging and UV-induced skin disorders. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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7 pages, 417 KB  
Brief Report
The Impact of Sunlight Exposure on Postoperative Hypoparathyroidism: A Retrospective Analysis from Two Greek Centers
by Angeliki Chorti, Ioannis Pliakos, Moysis Moysidis, Aikaterini Smprini, Sohail Bakkar and Theodossis Papavramidis
J. Clin. Med. 2025, 14(13), 4418; https://doi.org/10.3390/jcm14134418 - 21 Jun 2025
Viewed by 381
Abstract
Background: Postoperative hypoparathyroidism is a common complication of thyroid surgery. Sunlight is a natural source of ultraviolet B (UVB) radiation, which facilitates the synthesis of vitamin D3 in the skin. Inadequate sunlight exposure has been linked to vitamin D deficiency, potentially exacerbating the [...] Read more.
Background: Postoperative hypoparathyroidism is a common complication of thyroid surgery. Sunlight is a natural source of ultraviolet B (UVB) radiation, which facilitates the synthesis of vitamin D3 in the skin. Inadequate sunlight exposure has been linked to vitamin D deficiency, potentially exacerbating the risk of hypocalcemia in patients undergoing thyroid surgery. The aim of the present study is to evaluate the effect of sunshine levels on postoperative hypoparathyroidism. Method: We retrospectively evaluated patients that underwent total thyroidectomies at two different centers (Thessaloniki and Rhodes) by the same surgical team from 2021 to 2023 in terms of postoperative hypoparathyroidism. We compared the sunshine levels at each center the year before surgery and correlated them with postoperative levels of parathyroid hormone, serum ionized calcium, and phosphorus. Results: One-hundred twenty patients (Group Thessaloniki = 60 patients, Group Rhodes = 60 patients) who were matched for demographic characteristics and type of thyroid disease and surgery were enrolled in our study. The sunshine levels were different between the two centers (Rhodes > Thessaloniki, p < 0.001). It was found that sunshine levels affect preoperative serum ionized calcium (p = 0.002) and postoperative parathyroid hormone levels (p = 0.025). Conclusions: Sunlight exposure levels may play a crucial role in preventing postoperative hypoparathyroidism. Patients living in locations with higher sunshine levels may have lower rates of postoperative hypoparathyroidism. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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22 pages, 12881 KB  
Article
TOPK Drives IL19-Mediated Crosstalk Between Cancer Cells and Fibroblasts to Promote Solar UV-Induced Skin Damage and Carcinogenesis
by Asad U. Khan, Qiushi Wang, Eunmiri Roh, Sally E. Dickinson, Georg T. Wondrak, Clara Curiel-Lewandowski, Ann M. Bode and Tianshun Zhang
Cancers 2025, 17(13), 2067; https://doi.org/10.3390/cancers17132067 - 20 Jun 2025
Viewed by 712
Abstract
Background/Objectives: Non-melanoma skin cancer (NMSC) is among the most common cancers in the United States, with solar ultraviolet (UV) radiation being a primary etiological factor. T-LAK cell-originated protein kinase (TOPK), a serine/threonine kinase activated by solar UV, has been implicated in skin carcinogenesis. [...] Read more.
Background/Objectives: Non-melanoma skin cancer (NMSC) is among the most common cancers in the United States, with solar ultraviolet (UV) radiation being a primary etiological factor. T-LAK cell-originated protein kinase (TOPK), a serine/threonine kinase activated by solar UV, has been implicated in skin carcinogenesis. This study aimed to investigate the mechanistic role of TOPK in solar UV-induced skin damage and tumor development. Methods: RNA sequencing (RNA-seq) was performed on skin tissues from wild-type (WT) and TOPK knockout (KO) mice, with or without solar UV exposure, to identify TOPK-regulated genes and pathways. Follow-up experiments using Western blotting, immunofluorescence, and luciferase assays were conducted in vitro and in vivo. Functional assays included 3D spheroid and Transwell co-culture systems involving cutaneous squamous cell carcinoma (cSCC) and fibroblast cells. Results: TOPK deletion altered gene expression profiles and inhibited solar UV-induced activation of multiple signaling pathways, including cytokine–cytokine receptor interaction, PI3K/AKT, MAPKs, PKG, cAMP, and calcium signaling. RNA-seq and protein analyses identified interleukin-19 (IL19) as a key downstream effector suppressed by TOPK deletion. In cSCC and fibroblast cells, TOPK knockdown reduced IL19 expression and secretion. IL19 promoted cSCC growth and activated PI3K/AKT, ERK, and TOPK pathways. Additionally, chronic TGFβ exposure increased IL19 expression and activated fibroblasts, as indicated by elevated αSMA and FAPα levels. Conclusions: These findings establish TOPK as a central regulator of solar UV-induced skin carcinogenesis, partially via modulation of IL19 signaling and fibroblast activation. Targeting TOPK may offer a novel strategy for the prevention and treatment of NMSC. Full article
(This article belongs to the Special Issue The Advance of Biomarker-Driven Targeted Therapies in Cancer)
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18 pages, 4043 KB  
Article
Clinico-Pathologic Profile of a Cohort of Patients with Actinic Keratosis in a Tertiary Center in Romania
by Cristina Soare, Elena Codruța Cozma, Andrei Ludovic Poroșnicu, Daniel Alin Cristian, Draga Maria Mandi, Călin Giurcăneanu and Vlad Mihai Voiculescu
Cancers 2025, 17(12), 1923; https://doi.org/10.3390/cancers17121923 - 10 Jun 2025
Viewed by 528
Abstract
Background/Objectives: Actinic keratosis (AK) is considered to be the most common form of in situ carcinoma and typically arises on skin that has been chronically exposed to ultraviolet radiation. The need for early diagnosis, using non-invasive methods, has allowed for a non-surgical approach [...] Read more.
Background/Objectives: Actinic keratosis (AK) is considered to be the most common form of in situ carcinoma and typically arises on skin that has been chronically exposed to ultraviolet radiation. The need for early diagnosis, using non-invasive methods, has allowed for a non-surgical approach to these conditions with a significant impact on the quality of life of patients. Methods: A retrospective study was conducted on 58 patients diagnosed with AK who underwent surgical excision at a tertiary center in Bucharest, Romania between 2018 and 2023. Clinical parameters (age, sex, lesion size, anatomical location, comorbidities) and histopathological variables (AK subtype, KIN grade, pleomorphism, solar elastosis, inflammatory infiltrate) were analyzed. Statistical associations between histological findings and clinical features were assessed using Fisher’s exact test. Conclusions: The study confirmed a predominance of AK among elderly patients, with hypertrophic lesions and moderate dysplasia (KIN II) being most common. Higher KIN grades correlated significantly with more severe pleomorphism, solar elastosis, and inflammatory response, suggesting progressive UV-induced skin damage. The findings underscore the importance of clinicopathological correlation for risk stratification and support the integration of non-invasive diagnostic tools to improve early detection and management of AK. Full article
(This article belongs to the Section Clinical Research of Cancer)
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13 pages, 376 KB  
Article
Relationship Between Facial Melasma and Ocular Photoaging Diseases
by Lunla Udomwech, Chime Eden and Weeratian Tawanwongsri
Med. Sci. 2025, 13(2), 61; https://doi.org/10.3390/medsci13020061 - 16 May 2025
Viewed by 1336
Abstract
Background/Objectives: Facial melasma is a common, chronic, and relapsing hyperpigmentation disorder, affecting up to 40% of adult women in Southeast Asia. Although most cases are mild, the condition may have a considerable psychological impact. Ocular photoaging diseases are also common and have been [...] Read more.
Background/Objectives: Facial melasma is a common, chronic, and relapsing hyperpigmentation disorder, affecting up to 40% of adult women in Southeast Asia. Although most cases are mild, the condition may have a considerable psychological impact. Ocular photoaging diseases are also common and have been increasingly recognized in aging populations exposed to chronic sunlight. Ultraviolet (UV) radiation is implicated in both melasma and ocular photoaging; however, their relationship remains unclear. Methods: This cross-sectional study investigated the association between facial melasma and UV-induced ocular conditions among 315 participants aged 30–80 years at Walailak University Hospital, Thailand. Facial melasma was diagnosed clinically and dermoscopically, with severity assessed using the modified Melasma Area Severity Index. Ophthalmological examinations evaluated UV-related ocular conditions, including pinguecula, pterygium, climatic droplet keratopathy, cataracts, and age-related macular degeneration. Logistic regression analyses were performed, adjusting for age, sex, and sun exposure. Results: Facial melasma was identified in 66.0% of participants (n = 208), and nuclear cataracts were significantly associated with melasma (adjusted odds ratio, 2.590; 95% confidence interval, 1.410–4.770; p = 0.002). Additionally, melasma severity correlated with nuclear cataract severity (ρ = 0.186, p = 0.001). Other ocular conditions were not significantly associated with melasma. Conclusions: These findings suggest a shared UV-related pathogenesis between facial melasma and nuclear cataracts. Sun protection measures, including regular sunscreen use, UV-blocking eyewear, and wide-brimmed hats, may help mitigate the risk of both conditions. Further multicenter studies are warranted to confirm these findings and explore the underlying mechanisms. Full article
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8 pages, 3821 KB  
Communication
Ultraviolet Background Radiation from Not-So-Dark Matter in the Galactic Halo
by Richard Conn Henry, Jayant Murthy and James Overduin
Universe 2025, 11(5), 148; https://doi.org/10.3390/universe11050148 - 3 May 2025
Viewed by 440
Abstract
Murthy et al. (2025) (hereafter Paper I) have recently reported the discovery of unexpectedly bright diffuse extreme-ultraviolet radiation at high latitudes in both the Northern and Southern Galactic Hemispheres. After correction for extinction by the total interstellar dust in the direction of each [...] Read more.
Murthy et al. (2025) (hereafter Paper I) have recently reported the discovery of unexpectedly bright diffuse extreme-ultraviolet radiation at high latitudes in both the Northern and Southern Galactic Hemispheres. After correction for extinction by the total interstellar dust in the direction of each observation, the spectra are nearly identical, suggesting that the radiation has a unique source and likely originates in the halo of our galaxy. The observed spectrum extends down to 912 Å, the interstellar hydrogen absorption edge. Radiation even slightly short of that edge would, if ubiquitous, be sufficient to explain the high degree of ionization in our galaxy and throughout the universe. We hypothesize that this newly discovered radiation originates in the slow decay of dark matter. The intensity of the radiation implies that the decay cannot be via the weak interaction, suggesting the existence of a new, even weaker fundamental interaction, consistent with the exceedingly long decay lifetime required. Full article
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15 pages, 507 KB  
Review
Spectropolarimetry for Discerning Geometry and Structure in Circumstellar Media of Hot Massive Stars
by Richard Ignace, Kenneth G. Gayley, Roberto Casini, Paul Scowen, Christiana Erba and Jeremy Drake
Galaxies 2025, 13(2), 40; https://doi.org/10.3390/galaxies13020040 - 11 Apr 2025
Cited by 2 | Viewed by 725
Abstract
Spectropolarimetric techniques are a mainstay of astrophysical inquiry, ranging from Solar System objects to the Cosmic Background Radiation. This review highlights applications of stellar polarimetry for massive hot stars, particularly in the context of ultraviolet (UV) spaceborne missions. The prevalence of binarity in [...] Read more.
Spectropolarimetric techniques are a mainstay of astrophysical inquiry, ranging from Solar System objects to the Cosmic Background Radiation. This review highlights applications of stellar polarimetry for massive hot stars, particularly in the context of ultraviolet (UV) spaceborne missions. The prevalence of binarity in the massive star population and uncertainties regarding the degree of rotational criticality among hot stars raises important questions about stellar interactions, interior structure, and even the lifetimes of evolutionary phases. These uncertainties have consequences for stellar population synthesis calculations. Spectropolarimetry is a key tool for extracting information about stellar and binary geometries. We review methodologies involving electron scattering in circumstellar envelopes; gravity darkening from rapid rotation; spectral line effects, including the (a) “line effect”, (b) Öhman effect, and (c) Hanle effect; and the imprint of interstellar polarization on measurements. Finally, we describe the Polstar UV spectropolarimetric SMEX mission concept as one means for employing these diagnostics to clarify the state of high rotation and its impacts for massive stars. Full article
(This article belongs to the Special Issue Circumstellar Matter in Hot Star Systems)
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16 pages, 614 KB  
Review
The Impact of Dietary Intake of Furocoumarins and Furocoumarin-Rich Foods on the Risk of Cutaneous Melanoma: A Systematic Review
by Isabelle Kaiser, Anja Rappl, Lena S. Bolay, Annette B. Pfahlberg, Markus V. Heppt and Olaf Gefeller
Nutrients 2025, 17(8), 1296; https://doi.org/10.3390/nu17081296 - 8 Apr 2025
Cited by 1 | Viewed by 851
Abstract
Background/Objectives: Furocoumarins, chemical compounds found in many plant species, have a photosensitizing effect on the skin when applied topically and, by interacting with ultraviolet radiation (UVR), stimulate melanoma cells to proliferate. Whether dietary intake of furocoumarins acts as a melanoma risk factor has [...] Read more.
Background/Objectives: Furocoumarins, chemical compounds found in many plant species, have a photosensitizing effect on the skin when applied topically and, by interacting with ultraviolet radiation (UVR), stimulate melanoma cells to proliferate. Whether dietary intake of furocoumarins acts as a melanoma risk factor has been investigated in several epidemiological studies, which are synthesized in our systematic review. Methods: The study protocol was registered with PROSPERO (registration number: CRD42023428596). We conducted an in-depth literature search in three databases coupled with forward and backward citation tracking and expert consultations to identify all epidemiological studies, irrespective of their design, addressing the association between a furocoumarin-containing diet and melanoma risk. We extracted information on the study details and results in a standardized manner and evaluated the risk of bias of the results using the Joanna Briggs Institute’s critical appraisal tools. Results: We identified 20 publications based on 19 different studies providing information on the association between dietary furocoumarin intake and melanoma risk. We refrained from a meta-analytical synthesis of the results because of the large heterogeneity in exposure assessment, operationalization of furocoumarin intake in the analyses, and analytical methods of the studies. In a qualitative synthesis, we found moderate evidence supporting the notion that dietary furocoumarin intake at higher levels acts as a risk factor for cutaneous melanoma. Conclusions: Our systematic review provides an overview of the current epidemiological evidence, but it could not clearly answer whether and to what extent dietary furocoumarin intake increases melanoma risk. Future epidemiological analyses focusing on this topic require more comprehensive dietary and UVR exposure data to better characterize the individual total furocoumarin intake and its interplay with UVR exposure patterns. Full article
(This article belongs to the Special Issue Nutritional Epidemiology of Cancer)
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24 pages, 6008 KB  
Article
Phlorizin Protects Against Oxidative Stress and Inflammation in Age-Related Macular Degeneration Model
by Zhen-Yu Liao, Chih-Yu Hung, Yu-Jou Hsu, I-Chia Liang, Yi-Chun Chen, Chao-Hsien Sung and Chi-Feng Hung
Biomolecules 2025, 15(4), 523; https://doi.org/10.3390/biom15040523 - 3 Apr 2025
Cited by 1 | Viewed by 1094
Abstract
Background:Sweet Tea (Lithocarpus polystachyus Rehd.), a traditional ethnobotanical medicine, contains phlorizin, a dihydrochalcone compound with antioxidative and anti-inflammatory properties. Given the critical role of oxidative stress and inflammation in age-related macular degeneration (AMD), this study tested the hypothesis that phlorizin mitigates oxidative [...] Read more.
Background:Sweet Tea (Lithocarpus polystachyus Rehd.), a traditional ethnobotanical medicine, contains phlorizin, a dihydrochalcone compound with antioxidative and anti-inflammatory properties. Given the critical role of oxidative stress and inflammation in age-related macular degeneration (AMD), this study tested the hypothesis that phlorizin mitigates oxidative damage and inflammation in AMD models, thereby offering therapeutic potential. Materials and Methods: Adult retinal pigmented epithelial cells (ARPE-19) were pre-treated with phlorizin (0.01–0.1 μM) and subjected to oxidative stress induced by ultraviolet A (UVA) radiation or sodium iodate (NaIO3). Cell viability, reactive oxygen species (ROS) production, MAPK/NF-κB signaling, and the level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and pro-angiogenic factors (VEGF, MMP2, MMP9) expression were assessed using MTT assays, fluorescence imaging, Western blotting, and RT-qPCR. In vivo, a laser-induced choroidal neovascularization (CNV) mouse model was used to evaluate phlorizin’s effects on CNV formation and vascular leakage via fundus photography and fluorescence angiography. Result: Phlorizin significantly enhanced cell viability, reduced ROS production, inhibited MAPK/NF-κB activation, and downregulated inflammatory and angiogenic mediators. In vivo studies confirmed the reduced CNV formation and vascular leakage following the phlorizin treatment. Conclusions: Phlorizin demonstrated significant protective effects against oxidative stress and inflammation, highlighting its therapeutic potential for treating AMD. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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14 pages, 1819 KB  
Article
Ultraviolet B Exposure Does Not Influence the Expression of YAP mRNA in Human Epidermal Keratinocytes—Preliminary Study
by Igor Aleksander Bednarski, Izabela Dróżdż, Magdalena Ciążyńska, Karolina Wódz, Joanna Narbutt and Aleksandra Lesiak
Biomedicines 2025, 13(3), 596; https://doi.org/10.3390/biomedicines13030596 - 1 Mar 2025
Viewed by 812
Abstract
Background: The causal relationship between exposure to ultraviolet radiation and the development of skin cancers requires constant research for possible orchestrating mechanisms. In recent years, the Hippo pathway, along with its effector protein YAP, became implicated in cutaneous carcinogenesis; however, Hippo pathway regulation [...] Read more.
Background: The causal relationship between exposure to ultraviolet radiation and the development of skin cancers requires constant research for possible orchestrating mechanisms. In recent years, the Hippo pathway, along with its effector protein YAP, became implicated in cutaneous carcinogenesis; however, Hippo pathway regulation by ultraviolet radiation has not been described thoroughly. In order to address this issue, we focused on how different doses of ultraviolet B affect Hippo signaling pathway components and its upstream regulators, JNK1/2 and ABL1, in human keratinocytes. Additionally, we decided to determine how silencing of YAP influences Hippo pathway component expression. Methods: Primary epidermal keratinocytes were irradiated using UVB lamps with increasing doses of ultraviolet B radiation (including 311 nm UVB). Real-time PCR was used to determine the mRNA levels of each investigated gene. The experiment was then performed after YAP silencing using siRNA transfection. Additionally, we determined the mRNA expression of Hippo pathway components in an A431 cSCC cell line. Results: We observed that YAP mRNA expression in the A431 cell line was insignificant in comparison to control, while in the case of LATS1/2, a significant increase was noted. UVB irradiation did not change the levels of YAP mRNA expression in human epidermal keratinocytes. LATS1, LATS2, ABL1 and MAP4K4 mRNA expression was significantly upregulated after UVB irradiation in non-YAP-silenced keratinocytes in a dose-dependent manner, while after YAP silencing, only LATS2 and ABL1 showed significant mRNA upregulation. The 311 nm UVB irradiation resulted in significant, dose-dependent mRNA upregulation in non-YAP-silenced keratinocytes for LATS1, ABL1 and MAP4K4. After YAP silencing, a significant change in mRNA expression was present only in the case of ABL1. Conclusions: YAP mRNA expression does not significantly increase after exposure to UVB; however, it upregulates the expression of its proven (LATS1/2, JNK1/2) regulators, suggesting that in real-life settings, UV-induced dysregulation of the Hippo pathway may not be limited to YAP. Full article
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19 pages, 3588 KB  
Article
A Proprietary Punica granatum pericarp Extract, Its Antioxidant Properties Using Multi-Radical Assays and Protection Against UVA-Induced Damages in a Reconstructed Human Skin Model
by Steve Thomas Pannakal, Steven Durand, Julie Gizard, Peggy Sextius, Emilie Planel, Emilie Warrick, Damien Lelievre, Celine Lelievre, Joan Eilstein, Floriane Beaumard, Arpita Prasad, Sanketh Shetty, Arun Duraisamy, Kumar Gaurav, Sherluck John, Adrien Benazzouz, Xavier Fastinger, Dhimoy Roy and Vishal Sharma
Antioxidants 2025, 14(3), 301; https://doi.org/10.3390/antiox14030301 - 28 Feb 2025
Cited by 1 | Viewed by 2078
Abstract
Background: Within the solar ultraviolet (UV) spectrum, ultraviolet A rays (UVA, 320–400 nm), although less energetic than ultraviolet B rays (UVB, 280–320 nm), constitute at least 95% of solar UV radiation that penetrates deep into the skin The UV rays are associated with [...] Read more.
Background: Within the solar ultraviolet (UV) spectrum, ultraviolet A rays (UVA, 320–400 nm), although less energetic than ultraviolet B rays (UVB, 280–320 nm), constitute at least 95% of solar UV radiation that penetrates deep into the skin The UV rays are associated with both epidermal and dermal damage resulting from the generation of reactive oxygen species (ROS). Among them, the longest UVA wavelengths (UVA1, 340–400 nm) can represent up to 75% of the total UV energy. Therefore, UVA radiation is linked to various acute and chronic conditions, including increased skin pigmentation and photoaging. Despite many advances in the skin photoprotection category, there is still a growing demand for natural daily photoprotection active ingredients that offer broad protection against skin damage caused by UVA exposure. In our quest to discover new, disruptive, next generation of photoprotective ingredients, we were drawn to pomegranate, based on its diverse polyphenolic profile. We investigated the pericarp of the fruit, so far considered as byproducts of the pomegranate supply chain, to design a novel patented extract “POMAOX” with a desired spectrum of phenolic components comprising of αβ-punicalagins, αβ-punicalins and ellagic acid. Methods: Antioxidant properties of POMAOX were measured using in-tubo standard tests capable of revealing a battery of radical oxygen species (ROS): peroxyl radical (ORAC), singlet oxygen (SOAC), superoxide anion (SORAC), peroxynitrite (NORAC), and hydroxyl radical (HORAC). In vitro, confirmation of antioxidant properties was first performed by evaluating protection against UVA-induced lipid peroxidation in human dermal fibroblasts (HDF), via the release of 8 iso-prostanes. The protection offered by POMAOX was further validated in a 3D in vitro reconstructed T-SkinTM model, by analyzing tissue viability/morphology and measuring the release of Matrix Metallopeptidase 1 (MMP-1) & pro-inflammatory mediators (IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNF-α) after UVA1 exposure. Results: POMAOX displayed strong antioxidant activity against peroxynitrite (NORAC) at 1.0–3.0 ppm, comparable to the reference vitaminC, as well as singlet oxygen (SOAC) at 220 ppm, and superoxide radicals with a SORAC value of 500 ppm. Additionally, POMAOX demonstrated strong photoprotection benefit at 0.001% concentration, offering up to 74% protection against UVA-induced lipid peroxidation on HDF, in a similar range as the positive reference, Vitamin E at 0.002% (50 µM), and with higher efficacy than ellagic acid alone at 5 µM. Moreover, our pomegranate-derived extract delivered photoprotection at 0.001%, mitigating dermal damages induced by UVA1, through inhibition of MMP-1 and significant inhibition of pro-inflammatory mediators release (including IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNFα) on an in vitro reconstructed full-thickness human skin model with a similar level of protection to that of Vitamin C tested at 0.035% (200 µM). Conclusions: Overall, the novel pomegranate-derived extract “POMAOX” significantly reduced the impact of UVA on human skin, due to its broad-spectrum antioxidant profile. These findings suggest that POMAOX could offer enhanced protection against the detrimental effects of UV exposure, addressing the growing consumer demand for strong photoprotection with skincare benefits. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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Article
Relationship Between Epidermal Matrix Metalloproteinase-1 and Dermal Collagen Reduction in Skin Subjected to Chronic Sun Exposure
by Ushio Hanai, Keigo Kawabata, Yotaro Tsunoda, Hitoshi Nemoto, Kotaro Imagawa, Ayumi Kusaka-Kikushima, Yoshito Takahashi, Hiroyuki Yoshida and Tadashi Akamatsu
J. Clin. Med. 2025, 14(5), 1433; https://doi.org/10.3390/jcm14051433 - 20 Feb 2025
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Abstract
Background/Objectives: Temporary decreases in dermal collagen caused by artificial ultraviolet exposure are largely affected by increased epidermis-derived matrix metalloproteinase (MMP)-1 levels. However, the role of epidermal MMP-1 in dermal tissue remodeling induced by chronic sun exposure remains unclear. This study aimed to clarify [...] Read more.
Background/Objectives: Temporary decreases in dermal collagen caused by artificial ultraviolet exposure are largely affected by increased epidermis-derived matrix metalloproteinase (MMP)-1 levels. However, the role of epidermal MMP-1 in dermal tissue remodeling induced by chronic sun exposure remains unclear. This study aimed to clarify the involvement of epidermal and dermal MMP-1 in dermal collagen reduction induced by chronic sun exposure. Methods: Immunofluorescent staining of 30 facial skin tissue samples was performed to visualize MMP-1. The fluorescence intensity of epidermal MMP-1 observed on microscopic images was analyzed in relation to the severity of dermal tissue remodeling and the dermal collagen fiber density. A similar correlation analysis of the number of dermal MMP-1-positive cells was also performed. Results: Epidermal MMP-1 was observed in the stratum spinosum of skin without severe tissue remodeling; however, in skin with severe dermal tissue remodeling, MMP-1 was localized throughout the epidermis. The epidermal MMP-1 signal area and dermal collagen fiber density were negatively correlated (ρ = −0.383; p = 0.0002; n = 90). However, the ratio of dermal MMP-1-positive cells to total dermal cells was only negatively correlated with the collagen fiber density in skin that was not severely remodeled (ρ = −0.746; p = 0.001; n = 15). Conclusions: Epidermal MMP-1 is involved in the tissue remodeling of skin that is subjected to chronic sun exposure and short-term ultraviolet radiation exposure. However, dermal-cell-derived MMP-1 may be involved in biological processes that require an immediate collagen degradation response. The results of this study demonstrate the importance of controlling epidermal MMP-1 to inhibit dermal tissue remodeling induced by chronic sun exposure and provide new insights that are beneficial to the development of anti-photoaging skincare cosmetics. Full article
(This article belongs to the Section Dermatology)
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