Search Results (4,455)

Ultraviolet (UV) radiation is a major environmental factor contributing to photoaging, oxidative stress, inflammation, DNA damage, and photocarcinogenesis. Conventional UV filters, although widely used in sunscreen formulations, are associated with limitations including photoinstability, photocatalytic ROS generation, potential toxicity, and environmental concerns. In recent years, plant-mediated nanomaterials have emerged as promising multifunctional photoprotective systems, combining UV attenuation with antioxidant, anti-inflammatory, and biologically adaptive properties. Plant extracts are increasingly used as reducing and stabilising agents in the green synthesis of metal and metal oxide nanoparticles. Among these, ZnO and TiO₂ serve as established inorganic UV filters, whereas Ag and Au nanoparticles have primarily been investigated for their antioxidant, anti-inflammatory, antimicrobial, and ROS-modulating properties, which may indirectly enhance photoprotection. In parallel, plant-derived organic nanoparticles and herbal nanocomposites have demonstrated enhanced biocompatibility and multifunctional performance. This review critically examines the current landscape of plant-mediated photoprotective nanomaterials, focusing on the mechanistic interplay among optical UV attenuation, reactive oxygen species (ROS) modulation, and cellular signalling regulation. Particular emphasis is placed on structure–function relationships governing nanoparticle size, surface chemistry, bandgap properties, antioxidant behaviour, and biological interactions. The review further discusses translational challenges, including reproducibility, standardisation, scalability, long-term safety, regulatory classification, and limitations in benchmarking. Importantly, current evidence suggests that no single material system simultaneously optimises UV-blocking efficiency, ROS control, biocompatibility, and industrial scalability, highlighting the need for multifunctional hybrid design strategies. Finally, future perspectives involving predictive nanoengineering, computational modelling, machine learning-guided optimisation, and adaptive photoprotective systems are discussed as emerging directions for next-generation sustainable photoprotective technologies. Full article

Background/Objectives: Metatypical basal cell carcinoma (MTBCC) is a rare and aggressive variant of non-melanoma skin cancer (NMSC) characterised by overlapping histological features of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Owing to its increased propensity for local invasion, recurrence, and metastasis, MTBCC poses diagnostic and therapeutic challenges. This study aimed to characterise the epidemiological, histopathological, and clinical features of MTBCC and to evaluate temporal changes in tumour characteristics and aggressiveness before, during, and after the COVID-19 pandemic. Methods: A retrospective cohort study was conducted on 129 histologically confirmed MTBCC lesions diagnosed in the Pathology Department of the Mures Clinical County Hospital, Targu Mures, Romania, between January 2017 and December 2025. Demographic data, tumour location, histological subtypes, differentiation of the squamous component, aggressiveness parameters, and volumetric measurements of tumours and excision specimens were analysed. Volumetric analyses were restricted to cases with complete three-dimensional measurements. Statistical comparisons were performed across demographic variables and the following three time periods: pre-pandemic, pandemic, and post-pandemic. Results: The median age at diagnosis was 71 years, with a slight male predominance (p = 0.25) and a significant predominance of patients from urban areas (p < 0.001). Most tumours were located in the head and neck region. Mixed-type MTBCC was significantly associated with higher tumour aggressiveness (p = 0.0019) and with high-risk histological subtypes, particularly micronodular and adenoid–cystic variants. Tumour volume showed a significant inverse correlation with year of diagnosis (p = 0.0139; r = (−) 0.50), whereas excision specimen volume differed significantly according to year of diagnosis (p = 0.0425). Neither tumour volume nor excision specimen volume was associated with histopathological aggressiveness. Conclusions: Metatypical basal cell carcinoma is a rare skin malignancy in which biological behaviour appears to be determined primarily by histopathological architecture rather than tumour size. Mixed-type lesions were associated with significantly higher aggressiveness, underscoring the need for accurate histopathological assessment. These findings support a pathology-driven approach to management and emphasise the importance of adequate surgical treatment and long-term follow-up in patients with MTBCC. Full article

Introduction: Melanoma is a chronic disease that significantly affects patients’ daily functioning and emotional well-being. Beyond its somatic burden, it often leads to substantial changes in quality of life (QoL). This study aimed to assess illness acceptance among melanoma patients and examine its associations with selected clinical characteristics (disease stage, pruritus and time since diagnosis), psychological distress (depression and anxiety) and QoL. Materials and Methods: A cross-sectional study was conducted between June 2025 and February 2026 at two tertiary oncology centers in Poland. Initially, 191 consecutive melanoma patients were recruited, of whom 162 (58.6% men; mean age 59.8 ± 13.7 years) were included in the final analysis (response rate: 84.8%). Participants completed validated questionnaires assessing illness acceptance (Acceptance of Illness Scale (AIS)), depression (PHQ-9, HADS-D), anxiety (GAD-7, HADS-A), and QoL (DLQI). Statistical analyses were performed, with p < 0.05 considered statistically significant. Results: The mean AIS score was 13.28 ± 7.50 points, indicating a remarkably low level of illness acceptance. In the multivariable linear regression analysis, greater depressive symptoms (HADS-D: β = −1.16, 95% CI −1.79 to −0.54; p < 0.001) and more advanced melanoma stage (β = −1.52, 95% CI −2.92 to −0.12; p = 0.034) were independently associated with lower illness acceptance. In addition, illness acceptance showed significant correlations with depressive symptoms, anxiety symptoms, and dermatology-related QoL, whereas no significant associations were observed with most evaluated demographic and clinical variables. Conclusions: Patients with melanoma demonstrated remarkably low illness acceptance. Depressive symptoms and more advanced melanoma stage were independently associated with lower illness acceptance. These findings support the integration of psychological assessment into comprehensive melanoma care. Full article

Cutaneous melanoma and basal cell carcinoma (BCC) represent the two primary malignancies driven by solar ultraviolet (UV) radiation. To map the spatial topology and distance dependence of their mutational signatures, we deployed new analytical bioinformatics workflow utilizing two convergent strategies: a data-driven read-level phasing framework to discriminate between collateral mutational events versus independent ones and a hypothesis-driven spatial permutational simulation model to capture density-dependent local deviations. A whole-genome analysis employing this framework unexpectedly reveals two fundamentally distinct lesion-processing landscapes, present in both BCC and melanoma. While independent mutations consistently reproduce canonical UV signatures (SBS7a–c) in both tumor types, collateral mutations tell a distinct and more varied narrative between BCC and melanoma. These collateral mutations are unusually abundant for non-UV characteristics, such as age-related SBS1 and SBS5, and display a notable 3′ to 5′ asymmetry near UV-induced lesions in pyrimidine dimers. We also demonstrated that BCC displays a pronounced enrichment of dinucleotide base substitutions flanking UV-signature sites on the 3′ side, particularly CA>TG and CG>TA changes. Ultimately, these topological patterns in both tumors indicate that a primary photoproduct seeds secondary mutagenesis within its local chromatin environment, dramatically altering our understanding of UV-induced lesion processing. Full article

Background/Objectives: Skin cancer is a major health concern worldwide and has led to the quest for safer and more effective topical chemopreventive agents. In this study, the in vivo efficacy of a hydrogel formulation containing kaempferol and ferulic acid-loaded nanoparticles was evaluated for the management of DMBA-croton oil-induced skin cancer in Swiss albino mice. Methods: Drug-loaded nanoparticles prepared via nanoprecipitation were incorporated into hyaluronic acid to obtain single-drug (FAPG, KMPG) and dual-drug-loaded (FKMG) hydrogel formulations. Skin tumors were induced via DMBA as an initiator followed by croton oil as a promoter, with tumor onset observed after a similar latency period of approximately 5–6 weeks in all carcinogen-exposed groups. Treatment was initiated after week 6 and continued until week 16. Results: The gel formulation had a skin-compatible pH and the desired rheological and spreadability properties. The dual drug-loaded hydrogel formulation had a more controlled and prolonged release profile. Compared with the negative and vehicle control groups, the FKMG-treated group presented a marked reduction in tumor incidence and tumor burden, along with improved body weight gain. Biochemical analysis revealed the restoration of antioxidant and enzyme activity in treated animals, particularly in animals treated with FKMG. Histopathological examination revealed near-normal skin architecture in FKMG-treated mice, indicating strong protective effects. Additionally, significant downregulation of TNF-α and IL-6 suggested effective suppression of tumor-promoting inflammatory pathways. Conclusions: Overall, the FKMG formulation exhibited superior chemopreventive efficacy compared with the FAPG and KMPG treatments, highlighting its potential as a promising topical therapeutic strategy against chemically induced skin carcinogenesis. Full article

Ultraviolet B (UVB) radiation is a primary cause of DNA damage in the skin, which is often a precursor to skin cancer. Natural products represent a rich source of compounds with unexplored photoprotective properties. Our previous work identified 3-methoxybenzyl isothiocyanate (MBITC), a meadowfoam derivative, as a promising UVB-absorptive agent that reduces DNA damage and cell proliferation; however, its clinical use is limited by dose-dependent cytotoxicity. To address this, we synthesized a novel amide lipid conjugate of MBITC, N-(3-methoxybenzyl)eicos-5-enamide (MBA), and evaluated its photoprotective efficacy and mechanism of action. Our findings demonstrate that MBA exhibited remarkably reduced cytotoxicity compared to its parent compound, while effectively retaining its photoprotective properties. In human primary keratinocyte cultures, MBA significantly reduced UVB-induced DNA damage, as evidenced by a decrease in cyclobutane pyrimidine dimers (p < 0.05) and γ-H2A.X (p < 0.05). Furthermore, MBA increased the expression of DNA damage response (DDR) proteins and DNA damage-binding protein 1 (DDB1) (p < 0.05) and the activation of Ataxia Telangiectasia and Rad3-related protein (ATR) (p < 0.05), a master regulator of DDR and repair pathways. These findings suggest that MBA acts through direct UVB absorption and/or the engagement of DDR pathways following irradiation, highlighting its potential use as a novel photoprotective compound. Full article

Oleanolic acid is a naturally occurring pentacyclic triterpenoid with broad preclinical promise in inflammation, oxidative stress, liver injury, metabolic disorders, cancer-related models, skin disease, and wound repair. Its further development, however, is constrained by poor aqueous solubility, low and variable bioavailability, limited barrier transport, crystallinity, and strong dependence of biological response on the formulation used. These properties make oleanolic acid a useful example of a hydrophobic natural compound whose pharmacological performance is inseparable from delivery design. This review examines polymeric nanocarriers and polymer-assisted delivery platforms developed for oleanolic acid delivery. Polymeric nanocarriers discussed in the review include biodegradable PLA/PLGA nanoparticles, PEGylated polymeric nanoparticles, polymeric micelles, nanogels, hyaluronic-acid-based nanoprodrugs, and selected polymer-assisted hybrid nanostructures. Hydrogels, polymeric fiber membranes, local depots, and microneedle systems are included as route-enabling delivery platforms when the polymeric matrix directly contributes to OA incorporation, carrier stabilization, local retention, barrier bypass, or release control. Non-polymeric delivery systems are discussed only as comparators or when their performance depends on integration with a polymeric component. Rather than treating these carriers only as solubility enhancers, the review evaluates how polymer composition, carrier architecture, drug physical state, release behavior, and route of administration affect oleanolic acid exposure. Particular attention is given to controlled release, local retention, disease-oriented delivery, and critical quality attributes such as particle size, loading, encapsulation efficiency, solid-state form, stability, residual solvent, sterility, and batch-to-batch reproducibility. Representative quantitative data on carrier size, drug loading, encapsulation efficiency, release, stability, tissue exposure, and biological outcomes are compared to illustrate both formulation-specific performance and the substantial methodological heterogeneity of the available studies. The available evidence indicates that increased apparent solubility, increased biological exposure, and improved therapeutic response should be treated as related but distinct outcomes. The most realistic near-term opportunities may lie in local and tissue-targeted applications, including inflammatory skin disease, wound healing, dermal delivery, and osteoarthritis, where sustained target-site exposure may be more relevant than systemic bioavailability. Future progress will depend on demonstrating that each formulation provides reproducible, safe, and route-appropriate OA exposure, together with a measurable advantage over simpler delivery approaches. Full article

Background: Long-term mortality trends for melanoma and non-melanoma skin cancer (NMSC) in Hungary have not been comprehensively assessed. Methods: We conducted a retrospective nationwide study of deaths registered in Hungary between 1980 and 2020 among individuals aged 35 years or older, where melanoma (ICD-10 C43) or NMSC (ICD-10 C44) was recorded as the primary cause of death. Annual crude death rates (CDRs; overall and age-specific 35–64 and ≥65 years) and age-standardised death rates (ASDRs) per 100,000 population were calculated by sex. Trends were analysed using Joinpoint regression. Results: Overall, 18,857 skin cancer deaths, including 12,026 melanoma and 6831 NMSC deaths, were identified. Melanoma mortality was consistently higher in men. Among men, melanoma ASDR increased until 1994 and then stabilised, while crude mortality among older men continued to increase. Among women, the ASDR of melanoma increased until 1994 and subsequently declined. Crude mortality decreased after 2005 in women aged 35–64 years. Although NMSC mortality was lower than melanoma mortality, NMSC accounted for 36.2% of skin cancer deaths. In both sexes, NMSC mortality was concentrated in adults ≥ 65 years. In older women, crude NMSC mortality increased again after the mid-2000s, whereas ASDR remained broadly stable. Conclusions: Melanoma mortality trends in Hungary partially stabilised or improved after the mid-1990s, particularly in age-standardised analyses, but mortality remained high among older adults, especially among men. NMSC represented a substantial proportion of skin cancer deaths, with the burden concentrated in adults ≥ 65 years, supporting the inclusion of NMSC in routine mortality surveillance and disease burden assessments. Full article

Background/Objective: Melanoma is the most aggressive form of skin cancer and most common among fair-skinned people, and about 80% of fatalities are from skin lesions. The rise in deaths from melanoma worldwide has been related to a lack of access to healthcare, mostly in low-income nations. Melanoma therapy using current treatments, such as cisplatin, has been beneficial. However, it has been linked to irreversible DNA damage, whereas most current treatments are either ineffective or have intolerable side effects. This study investigated the cytotoxic effects of Leptospermum petersonii extracts on A375 melanoma cells and aimed to identify at least one putative bioactive compound. L. petersonii is a well-established medicinal plant for its antimicrobial activities, and its leaves are reported to contain essential oils that suppress fungus development. However, no previous research on the effects of this herb on cancer has been reported. Methods: The sequential extraction was conducted by soaking the leaves in hexane, ethyl acetate, and methanol. The chemical 6-methyltectochrysin was effectively isolated from L. petersonii and showed cytotoxicity against melanoma cancer cells. Caspase Glo 3/7 and Annexin V-FITC–PI apoptotic tests were performed following 6-methyltectochrysin administration. Results: The findings showed cytotoxicity and possible apoptosis induction in A375 cells, and further examination using relative expression analysis revealed an increase in the pro-apoptotic Bax and a decrease in the anti-apoptotic Bcl-2 gene. Conclusions: Further research is needed to identify molecular pathways and targets of the compound 6-methyltectochrysin in melanoma cancer cells. Full article

Human pigmentation is a quantitative, tissue-specific, and temporally variable phenotype shaped by melanocyte biology, melanosome physiology, regulatory variation, environmental exposure, and population history. This narrative review examines how functional and population-based evidence supports—or limits—the translation of pigmentation genetics into forensic DNA phenotyping (FDP) and health-related applications. A structured search of MEDLINE/PubMed and Google Scholar was conducted through July 2026, prioritizing primary functional studies, independent validations, meta-analyses, and consensus documents. Current evidence supports polygenic and regulatory control of skin, hair, and iris pigmentation, but heterogeneous phenotype definitions, population composition, age, and environmental modulation constrain direct genotype-to-appearance inference. IrisPlex, HIrisPlex, and HIrisPlex-S provide validated probabilistic predictions for selected pigmentation categories; performance is less consistent for intermediate phenotypes, admixed populations, partial profiles, and settings lacking appropriate calibration. Associations with ultraviolet damage and cutaneous cancer are substantial but differ by cancer type, whereas evidence concerning vitamin D, melanin–drug interactions, and broader precision-medicine applications remains context-dependent or preliminary. Progress will require standardized phenotyping, globally representative datasets, transparent uncertainty reporting, and independent forensic and clinical validation. Full article

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer (NMSC) and represents the leading cause of NMSC-related deaths. Despite its growing global burden, comprehensive epidemiological and clinicopathological data from Easter Europe remains limited. This study aimed to evaluate the epidemiological, clinical, histopathological, and surgical characteristics of cSCC diagnosed before, during and after the COVID-19 pandemic. Methods: We conducted a retrospective, descriptive observational study including 332 lesions diagnosed between January 2017 and December 2025 at the Clinical Pathology Department of the Mureș Clinical County Hospital. Demographic, epidemiological, topographic, histopathologic, surgical, and volumetric parameters were analyzed. Tumours were stratified into low-, high-, and very-high-risk categories according to the National Comprehensive Cancer Network (NCCN) criteria. Results: The cohort demonstrated a significant male predominance (n = 193 vs. n = 139; p = 0.0355), with females presenting a higher median age (77 vs. 75; p = 0.0489). Lesions were predominantly located in the head and neck region (n = 216; p < 0.0001), which was significantly associated with very-high-risk tumours (p = 0.0051). Low-risk tumours accounted for 62.35% of cases, while high-risk and very-high-risk lesions comprised 19.88% and 17.77%, respectively (p < 0.0001). Ulcerations were strongly associated with very-high-risk tumours (p < 0.0001). Poor differentiation was more frequent outside the head and neck region (p < 0.0001) and varied significantly across the pandemic periods (p = 0.0349). Tumoral and excision volumes were higher in very-high-risk (p = 0.0070; p = 0.0004) and ulcerated tumours (p < 0.001), with a peak in volume during the COVID-19 period (p < 0.0001). A decrease through the years of diagnosis was observed in tumoral volumes (r = −0.2295; p < 0.0001) and patients showed a weak positive correlation with diagnosis year (r = +0.13; p = 0.019). Conclusions: The study provides an epidemiological and clinicopathological characterization of cSCC within one of the largest Romanian cohorts to date. Tumour aggressiveness was primarily driven by histopathological and topographical features rather than demographic factors. While the COVID-19 pandemic did not induce persistent changes in tumour risk profiles or surgical outcomes, it influenced diagnosis timing and tumour burden. These findings highlight the importance of incorporating temporal and emerging systemic factors, such as pandemics, and infectious events, into future epidemiological models to improve preparedness, early detection, future treatment schemes, and risk stratification in cSCC. Full article

Background/Objectives: Automated dermoscopic image analysis can assist research on early skin cancer detection, but deep learning models may learn acquisition-related shortcuts, including terminal hairs, illumination gradients, gel bubbles, shadows and measurement markings. This study evaluates a causal uncertainty-decomposed ensemble (CUDE) for confounding-aware skin-lesion classification within the ISIC 2019 benchmark setting. Methods: CUDE uses a structured variational autoencoder (SVAE) to impose separate lesion-relevant and acquisition-related nuisance latent heads. Three stochastic latent-space experts are trained on complementary streams and are integrated by a Dirichlet-based fusion module trained with nuisance sampling. The causal graph is used as a modeling prior rather than proof of causal identification. Results: Using a stratified internal split of the labeled ISIC 2019 training collection, CUDE achieved a balanced accuracy of 89.7% and an AUROC of 0.972. Under the predefined synthetic artifact protocol, CUDE showed a relative performance drop of 5.0%, compared with 9.6% for the deep ensemble. Deferring the 10% most uncertain cases increased non-deferred accuracy from 89.7% to 93.2% and reduced false-negative rates for melanoma, BCC and SCC in the non-deferred subset. Conclusions: Within the evaluated ISIC 2019 split and controlled synthetic corruption protocol, structured latent separation, stochastic expert diversity and Dirichlet fusion were associated with improved benchmark robustness and calibration. These results should not be interpreted as evidence of broad real-world robustness or clinical deployment readiness; external multi-center, device-diverse and skin-tone-diverse validation remains required. Full article

The integration of immunohistochemical biomarkers like PRAME (Preferentially Expressed Antigen in Melanoma) into the histomorphological assessment of melanocytic lesions is gaining prominence. While PRAME’s diagnostic value is widely recognized, its independent weight compared directly to classical morphology remains underexplored in large, challenging cohorts. This retrospective study quantifies the diagnostic utility of PRAME alongside traditional histomorphology in a high-risk cohort of 954 primary melanocytic lesions (335 nevi, 215 melanomas in situ, 404 invasive melanomas) where PRAME was clinically requested to resolve diagnostic ambiguity. Using Firth’s penalized likelihood regression, a baseline diagnostic model utilizing 13 histomorphological features was established and subsequently integrated with PRAME expression. The pure morphology baseline model demonstrated a high cross-validated area under the curve (AUC) of 0.969. As a standalone marker, PRAME achieved an AUC of 0.895, with a diffuse expression score of 4+ yielding peak specificity (94.3%) and moderate sensitivity (77.9%). Integrating PRAME into the morphological model significantly enhanced diagnostic accuracy (AUC: 0.980; p < 0.001), establishing PRAME as a dominant independent predictor of malignancy alongside core features like junctional atypia and upward melanocytes (Odds Ratio 19.08 for Score 4+). Analysis of discordant cases revealed that completely PRAME-negative melanomas were morphologically indistinguishable from typical PRAME-positive melanomas. Conversely, diffusely PRAME-positive (4+) nevi exhibited significantly higher rates of upward migrating melanocytes, constituting a critical diagnostic pitfall. In conclusion, while classic histomorphology remains the indispensable gold standard in dermatopathology, PRAME functions as a highly objective, reproducible tie-breaker. The synergistic integration of PRAME with morphological assessment effectively resolves diagnostic ambiguity and maximizes diagnostic confidence in challenging melanocytic lesions. Full article

Background: Immune checkpoint inhibitors and adoptive T-cell therapies have substantially improved cancer treatment outcomes, but their use is often limited by immune-related toxicities, including cytokine release syndrome. The role of interleukin (IL)-17A in tumor immunity remains controversial, hindering its therapeutic applications in cancer. A concern is that application of IL-17 blocking agents to release cytokine storms caused by tumor immunotherapy reverses anti-tumor immunity. Methods: In this study, we evaluated the effect of IL-17A blockade alone and in combination with anti–PD (programmed cell death)-1 therapy or tumor-specific CD8⁺ T cells in melanoma, colon, and lung tumors, and in UVB-induced skin carcinogenesis. Results: Our results showed that blocking IL-17A inhibited tumor development, and did not impair the efficacy of tumor immunotherapies with checkpoint inhibitors or tumor-specific T cells. Combined treatment with anti-IL-17A and anti-PD-1 antibodies significantly enhanced tumor suppression compared to single-agent therapies in all tested tumor models. Moreover, IL-17A blockade improved the efficacy of adoptive CD8⁺ T-cell therapy. Mechanistic analyses revealed that the combination therapy increased infiltration of activated antigen-specific CD8⁺ T cells in tumors. In none of the tested tumor models did IL-17A blockade negatively affect the efficacy of tumor immunotherapy with checkpoint inhibitors or T-cell therapy. Conclusions: These findings suggest that the combined application of anti-IL-17A blocking agents with current tumor immunotherapy at the same time is a promising strategy to enhance the efficacy and potentially diminish immune-related adverse effects. Full article

Eosinophils are tissue-adapted granulocytes with important roles in host defense, immune regulation, barrier responses, and inflammatory disease. Beyond classical degranulation, activated eosinophils can release eosinophil extracellular traps (EETs), extracellular DNA and protein structures that arise through cytolytic nuclear EETosis or rapid mitochondrial DNA (mtDNA) release. These traps may contribute to host protection by immobilizing pathogens and concentrating eosinophil granule proteins at sites of mucosal or tissue inflammation. However, when EET formation is excessive, persistent, or insufficiently cleared, the same structures may promote epithelial injury, mucus viscosity, thromboinflammation, tissue remodeling, fibrosis, and chronic eosinophilic inflammation. This review summarizes the cellular mechanisms, structural organization, inducing stimuli, and disease relevance of EETs. Particular attention is given to infectious settings, eosinophilic airway and middle-ear disease, systemic vasculitic and hypereosinophilic disorders, inflammatory skin and ocular diseases, eosinophilic gastrointestinal disease, and cancer. Current evidence indicates that EETs should be interpreted as context-dependent eosinophil effector structures with dual biological potential. Although their mechanistic relevance is increasingly recognized, further histological, functional, and clinical validation is needed before EETs can be established as reliable biomarkers or therapeutic targets. Full article