Search Results (560)

Carvone is a naturally occurring monoterpene and the principal volatile constituent of spearmint (Mentha spicata) and caraway (Carum carvi), plants long used as carminative, digestive, antimicrobial, and flavoring agents. The compound exists as two enantiomers—S-(+)-carvone (predominantly associated with caraway) and R-(−)-carvone (predominantly associated with spearmint)—widely used in food, fragrance, and herbal preparations. Although carvone is a naturally occurring compound, the material used in experimental studies may be synthetically produced, isolated from plant essential oils, or used as a racemic or stereochemically enriched preparation. This review synthesizes evidence from 108 literature sources, complemented by PubChem (1535 records, accessed on 14 July 2026) and ChEMBL (136 records, accessed on 14 July 2026) bioassay data, to compile carvone’s molecular targets and biological activities and align the pharmacological evidence with traditional uses. We identified 45 molecular targets and 99 documented biological activities across 38 classes, spanning evidence tiers from comprehensively characterized (Tier A/B) to screening-level observations (Tier C/D), each assigned a four-tier evidence grade (A/B/C/D). Tier A targets comprise the aryl hydrocarbon receptor (AhR) and the GABA-A receptor. Negative results are reported to prevent publication bias, including NCI-60 inactivity across 55 cancer cell lines and a comprehensive counterscreen of steroid/nuclear receptors, human protein kinases, phosphatases, and HSP90—all inactive. The aryl hydrocarbon receptor emerges as the most robustly characterized target by the evidence-tiering criteria: both enantiomers act as noncompetitive allosteric antagonists, validated in vivo in mouse skin. This designation reflects the breadth and quality of evidence for AhR antagonism specifically, not a claim that AhR mediates all of carvone’s traditional or pharmacological effects. By mapping mechanistic evidence onto carvone’s traditional carminative, antimicrobial, and topical applications, this work provides a plausible mechanistic basis for several of the empirical uses documented in the ethnopharmacological literature. Full article

Skin health is increasingly recognised as a key determinant of overall well-being, and its decline is driven by multiple interconnected biological processes. Hydroxytyrosol (HT), an olive polyphenol, exhibits pleiotropic biological activities and has a potential role in supporting skin homeostasis. This narrative review critically evaluates the evidence on oral HT and HT-rich olive-derived nutraceuticals for skin health and healthy ageing with a focus on oxidative damage, inflammation, photoprotection, extracellular matrix (ECM) preservation, wound healing, and skin pigmentation conditions. HT exhibits high oral bioavailability and modulates antioxidant defences, inflammatory signalling, autophagy, apoptosis, and metabolic homeostasis. Preclinical studies consistently show protective effects against oxidative stress, ECM degradation, cellular senescence, photoageing, impaired wound healing, and ultraviolet-induced skin damage. Experimental evidence also indicates antiproliferative and pro-apoptotic effects in melanoma models through modulation of oncogenic signalling pathways, suggesting a potential role in skin cancer prevention. In vivo, oral HT administration improves glycative skin ageing, psoriasis, intestinal barrier integrity, and systemic inflammation. Clinical evidence supports systemic antioxidant and cardiometabolic benefits of purified HT and HT-rich formulations, while dermatological evidence remains preliminary for psoriasis, melasma, and wound healing. Overall, HT shows promise, but randomised controlled trials with validated dermatological endpoints are needed to confirm its clinical efficacy. Full article

Background/Objectives: Vitis vinifera is a rich source of polyphenolic compounds that are known for their benefits on skin health, including antioxidant, anti-inflammatory, and photoprotective effects. Red wines have shown a positive impact on cardiovascular disease, diabetes, and cancer prevention; however, evidence regarding their effects on skin biology remains scarce. This study evaluated red wine concentrates obtained from Cabernet Sauvignon and Merlot varieties, selected based on their previously demonstrated biological activities, to identify the samples with the highest potential for skin health applications by assessing their inhibitory activity against skin-related enzymes (tyrosinase, elastase, and collagenase), along with their effects on HaCaT cells, including cytotoxic, antioxidant, anti-inflammatory, and wound healing activities. Methods: Enzyme inhibition studies were based on spectrophotometric methods; the MTT and CV assays were carried out to test the cytotoxicity, and the DCFH-DA assay was employed to evaluate the antioxidant activity of the wine concentrates; wound healing potential was examined by the cell scratch assay, and anti-inflammatory activity was investigated using ELISA and qPCR analyses. PCA of the samples and their biological activity was performed as well. Results: Examined red wine concentrates exhibited significant enzyme inhibitory activity and showed no cytotoxicity on HaCaT cells up to the concentration of 50 μg/mL; the samples stimulated cell migration, inhibited intracellular ROS production in AAPH-stressed keratinocytes, and selectively modulated TNF-α-induced inflammatory responses, reducing IL-8 secretion while enhancing certain cytokine transcripts, underscoring the complexity of their bioactive effects. Conclusions: Red wine concentrates showed significant potential as skin-beneficial agents, demonstrating strong antiaging, marked cellular antioxidant effects and wound healing activity when applied at non-cytotoxic concentrations. Multivariate analysis revealed distinct bioactivity profiles among the wine concentrates. Full article

Background/Objectives: Triple negative breast cancer remains the most difficult breast cancer to treat as there are no specific targeted therapies. The tumor stroma is recognized as essential for the development of solid tumors. Cancer associated myofibroblasts are known to play a major role in the construction of a tumor microenvironment conducive to tumor progression. Therefore, we established a co-culture system to identify potential molecular targets controlling myofibroblast conversion. Methods: Co-cultures of MDA-MB-468 triple negative breast cancer cells and skin fibroblasts were either mixed prior to seeding or seeded individually on opposite sides of a culture dish and incubated in complete medium. Inhibitors were preincubated with cells for 1 h. Inflammatory cytokines were measured by ELISA. Proteins were analyzed using the Wes-Protein Simple System. Immunostaining was visualized using a Hamamatsu Photonics Nanozoomer. Statistical analysis was done by student’s t-test and one-way ANOVA. Results: The data indicate that co-culturing the cells promotes myofibroblast differentiation and cytokine release and this requires direct contact between the two cell types. Both myofibroblast conversion and cytokine release were prevented by inhibitors of TLR5, TGF-β and EDA-fibronectin. Conclusions: Data suggest that the TLR5 receptor on the MDA-MB-468 cells binds to EDA-fibronectin expressed by fibroblasts thus inducing inflammatory cytokine expression. Expression of EDA fibronectin is regulated through TGF-β whose synthesis is induced by TLR5 signaling in the tumor cells. The data are consistent with a model in which TLR5-mediated crosstalk between the cancer cells and the stromal fibroblasts creates a tissue microenvironment conducive to tumor growth and metastasis. Full article

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

NM averages 450 new cases of melanoma annually. Promotoras are community health workers in NM that provide health education and resources to the community. The project aims to determine if promotora education can improve the recognition of suspicious lesions, encouraging community members to seek care. Current literature focuses on the self-reported confidence of CHWs in recognizing skin cancer. A total of 54 promotoras were sampled through a Qualtrics quiz asking whether skin lesion photos are suspicious. Participants were also asked to rate their confidence in recognizing a suspicious skin lesion and comfort in addressing it from 1 to 5. Participants then read an educational flyer about the “ABCDEs” of melanoma before repeating the quiz/ratings. Wilcoxon signed-rank testing revealed significant increases in quiz scores (W = 220.5, p = 0.045), confidence (W = 44.0, p < 0.001), and comfort (W = 8.5, p < 0.001). Promotoras could be an additional line of defense against melanoma, helping save lives. Healthcare personnel with limited skin lesion knowledge could be an ideal future population for education. Full article

Background: Sun exposure guidance advises minimisation to reduce skin cancer risk, but advice is geared for white-skinned people. Melanin reduces skin synthesis of vitamin D from solar ultraviolet radiation (UVR), and adolescence is a key life-stage for bone mass acquisition. Methods: This prospective cohort study investigated year-round vitamin D status and its determinants in 143 South Asian adolescents (12–15 y; brown skin) living in Greater Manchester, UK. Serum 25OHD, personal UVR doses, time outdoors, and photoprotective measures were assessed across four seasons, and the findings were compared with those of 131 white Caucasian adolescents studied using identical protocols. Results: Severe vitamin D deficiency (25OHD < 25 nmol/L) was prevalent in South Asians, affecting 79% of girls and 69% of boys in winter, persisting year-round in 59% of girls and 23% of boys, and accompanied by winter PTH levels > the upper reference range in 59% of boys and 45% of girls. Personal UVR doses and time outdoors were lower on summer weekend days (boys 53 min, girls 60 min) vs. schooldays (boys 105 min, girls 108 min) in South Asians (p < 0.01). The findings contrasted with those in white Caucasians, where time outdoors was similar on summer weekend days and schooldays (weekend days: boys 131 min, girls 101 min, p < 0.01 vs. South Asians). Only 26% of South Asians vs. 86% of white Caucasians took a holiday abroad during the year, and days abroad significantly contributed to vitamin D status. Both groups had low oral vitamin D intake. Conclusions: Raising vitamin D status is crucial to prevent secondary hyperparathyroidism in South Asian adolescents and skin type-related sun exposure guidance is required. Full article

Background/Objectives: Extra virgin olive oil (EVOO), a key component of the Mediterranean diet, has attracted research interest because olive-derived phenolics demonstrate potential anticancer activity in experimental models. This review summarizes evidence concerning whole EVOO, phenolic-enriched EVOO, olive phenolic extracts, and the isolated compounds hydroxytyrosol, oleuropein, oleocanthal, and oleacein. Methods: A structured narrative search of PubMed, Web of Science, ScienceDirect, and Google Scholar was conducted for literature published between 2015 and 2025. Evidence was reviewed for breast, prostate, colorectal, pancreatic, bone, oral, liver, gastric, hematological, and brain cancers. Comparatively limited evidence concerning cervical, endometrial, ovarian, melanoma, non-melanoma skin, and thyroid cancers was summarized separately. Results: The molecular evidence was derived primarily from cell culture and animal studies using isolated phenolics and concentrated extracts. Preclinical studies indicate that EVOO phenolics may demonstrate anticancer activity through multiple mechanisms, including antioxidant activity, anti-inflammatory effects, cell cycle arrest, induction of apoptosis, inhibition of metastasis, anti-angiogenic activity, and modulation of key signaling pathways, such as PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Wnt/β-catenin, p53, and epithelial–mesenchymal transition-related pathways. Most molecular and pathway-level evidence was obtained using isolated phenolic compounds in cell culture or animal models, whereas evidence directly examining whole EVOO consumption was largely observational and substantially more limited. Experimental studies also reported that oleocanthal induced lysosomal membrane permeabilization, whereas hydroxytyrosol and oleuropein promoted mitochondria-mediated apoptosis. Furthermore, preclinical combination studies suggested enhanced tumor-cell sensitivity to selected chemotherapeutic, targeted, and immunotherapeutic agents. However, these effects have not been established in patients. Human evidence remains limited mainly to observational dietary associations and small exploratory interventions, with no conclusive demonstration of cancer prevention or therapeutic efficacy. Conclusions: Isolated EVOO-derived phenolic compounds demonstrated promising anticancer mechanisms in preclinical models. However, these results should not be directly extrapolated to dietary EVOO because experimentally administered doses, bioavailability, metabolism, and food-matrix interactions differ substantially from human dietary exposure. Therefore, well-designed studies using chemically characterized EVOO, pharmacokinetic investigations, and controlled human trials are required before dietary or clinical recommendations can be made. Full article

Background: Intraoperative frozen section analysis (FSA) is commonly used to verify conclusive margins after resection of non-melanoma skin cancer (NMSC) before reconstruction. However, its necessity in nodular basal cell carcinoma (nBCC) remains inconclusive following local flap reconstruction. Methods: Retrospectively, this quality assessment study investigated consecutive patients undergoing FSA-guided excision of nBCC following local flap reconstruction. The study evaluates predictors for free margins after the first FSA. Results: Between 1 January 2024 and 20 January 2025, 112 patients underwent removal of biopsy-verified nBCC followed by local flap reconstruction. Ninety-two patients (82.1%) had conclusive margins on the first FSA with excision margins of 3–5 mm. Of 20 FSA-positive results, 12 were confirmed as true positives on paraffin embedding while eight were false positives, giving FSA a positive predictive value of 60% (12/20); FSA missed residual tumor in four patients (3.6%), corresponding to a sensitivity of 75% and a specificity of 91.7%. Referral biopsy type (punch or curettage) did not significantly affect the accuracy in predicting the BCC subtype, and no demographic, tumor, or location variable was independently associated with margin status. Conclusions: In this study, FSA led to further resection in 20 of 112 cases; however, with a positive predictive value of 60%, it only prevented a second surgery in 10.7% of cases. Because the present analysis is retrospective and lacks oncological follow-up, our findings should be regarded as hypothesis-generating rather than confirmatory: selective omission of routine FSA in well-defined nBCC may shorten the operative time and simplify the workflow but require prospective validation. Full article

Melanoma is an aggressive skin cancer that has the potential to metastasize to the lymph nodes, lungs, liver, and brain. Therefore, the prevention and treatment of this condition are essential for achieving lower incidence rates and improving patient outcomes. Traditional treatment methods like surgery, radiation therapy, and chemotherapy have shown limited efficacy in the treatment of metastatic melanoma, and hence new treatment strategies have been developed. These recently developed treatment options include combining targeted therapies with immunotherapies to reduce drug resistance and improve overall effectiveness in preventing melanoma progression. Moreover, BRAF mutations are found in approximately 40–50% of cutaneous melanomas, and NRAS mutations in 15–25%, making these the two most common oncogenic drivers in the MAPK pathway. While alterations in other genes such as KRAS (~1.7%), HRAS (~1%), and MET (~2–4%) are relatively rare in melanoma, they still remain important to disease biology and are under investigation as potential therapeutic targets. These alterations may contribute to tumor progression, metastasis, and therapeutic resistance, highlighting the importance of continued investigation of targeted strategies in melanoma. This review aims to explore the role of each of these genes in melanoma, discusses their resistance mechanism, and summarizes preclinical and clinical trials involving drug combinations. By integrating current evidence on melanoma-associated genomic alterations with available targeted and immune approaches, this review aims to define molecular and clinical contexts that suggest potential treatment selections for melanoma patients. Full article

The prevalence of vitamin D deficiency has been noted to be of great concern to the population due to its association with multiple chronic ailments, such as those that affect the cardiovascular system, diabetes, bone diseases, and the immune system, and even some cancerous forms. The underlying mechanics are not well understood, but epidemiological and clinical research demonstrates notable correlations, correlated to different degrees by population, based on genetic, environmental, and lifestyle differences. The use of advanced machine learning methods in this study aimed to examine the association between serum vitamin D levels and chronic disease risk using the de-identified electronic health records from Intensive Care Unit (ICU) patients in the MIMIC-III database. A final cohort of 38,712 unique patients was selected after applying predefined inclusion and exclusion criteria, the data being used for machine learning model development and evaluation. To predict the status of chronic diseases based on vitamin D levels, supervised machine learning models were used: Logistic Regression (LR), Support Vector Machines (SVM), Random Forest (RF), and K-Nearest Neighbors (KNN). Data preprocessing involved strategies such as missing data imputation, normalization, and feature engineering to improve model training. The accuracy, precision, recall, F1-score, and receiver operating characteristic curve (ROC-AUC) were used to assess model performance. LR performed the best with the ROC-AUC of 92.5% and accuracy of 85.2%, and SVM was close behind the ROC-AUC: 90.9 percent. The chronic disease was associated with 2.1 times higher risk of chronic disease among people with severe vitamin D deficiency (p < 0.001), which was in agreement with earlier observational data. RF did not work as well (ROC-AUC: 87.7%) because it required higher dimensionality data, e.g., genetic and lifestyle parameters. The study shows the possible use of AI-based diagnostics in preventive medicine. As an example, presented vitamin D testing of high-risk population (e.g., increasing tests in old age, obesity, or dark-skinned population) adapted to ML-based risk assessment as well as supplementation plans could enhance this prevention. Full article

Background/Objectives: Skin cancer is one of the most common diseases worldwide, with a high mortality rate. Due to its ability to metastasize, the disease can progress to more serious stages over time. This article proposes a hybrid model based on feature engineering that will play a critical role in the early diagnosis of the disease. Methods: The developed model in this paper utilizes the well-known Vision Transformer (ViT) and Convolutional Neural Network (CNN) models for feature extraction from images in the dataset, while the FT-Transformer, Excel Former, SAINT, GRANDE, PTaRL, and TabTransformer architectures are used for feature extraction from clinical data. Furthermore, this study was developed using a very large pool of classifiers, including 13 classifiers. Fine-tuning was applied to improve the performance of the developed model. Channel attention mechanisms were incorporated into the study to ensure that the proposed model focuses on the diseased area. The PAD-UFES-20 dataset was used during the experiments. Class weighting was applied to the proposed model to prevent class-based imbalance in the PAD-UFES-20 dataset. Results: Six distinct CNN and four distinct ViT models were compared to the developed model. The developed model achieved a highly competitive Area Under the Curve (AUC) rate of 96.41%. The study was conducted using a dataset containing both clinical and imaging data. Conclusions: The proposed model is thought to help dermatologists diagnose skin cancer. Full article

Melanoma incidence is steadily on the rise but widespread prevention awareness and novel treatment approaches have substantially ameliorated the prognosis of the disease. Microphthalmia-associated transcription factor (MITF) is an essential transcription factor that plays a central role in the transcriptional circuitry of both normal melanocytes and malignant melanoma. Since over 30 years have elapsed since its discovery in mice, a large number of its target genes have been identified in pigment cells. Many upstream regulators of MITF have also been identified. Despite these substantial discoveries, MITF function, especially in melanomas, still remains elusive in several aspects. MITF is absolutely required for melanin formation because it transcribes virtually all genes required for the synthesis, storage, and transport of the pigment. Importantly, MITF is necessary for prevention of apoptosis in melanomas, at least at the early stages. However, in some metastases, MITF may be absent in most cells and its antiapoptotic function is evidently replaced by other proteins that not yet been fully identified. Furthermore, MITF is a specific nevus and melanoma marker, which is routinely used in immunohistochemistry, along with other markers, to distinguish pigmented and other skin lesions. In melanomas, high-MITF melanoma cell subpopulations are considered differentiated, i.e., pigmented and rapidly proliferating. In contrast, low-MITF cells proliferate slowly but are invasive with cancer stem cell-like properties. Although MITF activates mostly antiapoptotic and pro-proliferative genes, it also activates typical cell cycle inhibitors such as the p16 and p21 proteins. Here we discuss the issues of MITF multifunctionality in melanoma and associated research prospects. Full article

Usnic acid (UA), a prominent lichen secondary metabolite, exhibits a unique dual therapeutic profile in dermatology, though its clinical translation is limited by systemic hepatotoxicity and poor solubility. This review comprehensively evaluates the topical efficacy, molecular mechanisms, and advanced formulation strategies of UA enantiomers and UA-rich extracts. A literature search across PubMed, Scopus, and Google Scholar identified 36 original publications focusing on anti-melanoma activity, photoprotection, and tissue regeneration. In vitro studies demonstrate that UA induces apoptosis in resistant melanoma cell lines (A375, HTB-140) via extrinsic/intrinsic pathways, with (−)-UA effectively overcoming doxorubicin resistance. Conversely, in non-cancerous models, low concentrations of UA accelerate wound and burn healing by upregulating vascular endothelial growth factor (VEGF), stimulating fibroblast proliferation, and optimizing extracellular matrix remodeling while preventing hypertrophic scarring. To mitigate skin sensitization and systemic risks, advanced drug delivery systems—including liposomes, nanoemulsions, chitosan nanogels, and electrospun scaffolds—have been developed, significantly enhancing skin permeability and localized dermal retention. Ultimately, the development of bio-functionalized smart dressings and targeted nano-formulations represents the most viable path toward unlocking the full clinical potential of UA in modern dermatological and oncological care. Full article

Cutaneous squamous cell carcinoma (cSCC) is one of the most common non-melanoma skin cancers worldwide. Although surgery and adjuvant therapies are often effective, the treatment of high-risk or advanced lesions remains challenging due to recurrence, resistance, toxicity, and limited long-term control. Natural compounds have, therefore, gained interest as multi-target agents for cancer prevention and treatment. This systematic review aimed to evaluate the antitumoral activity of natural compounds against cSCC. A systematic literature search was conducted following PRISMA 2020 guidelines. Sixty studies met the inclusion criteria and were analyzed using a conservative, mechanism-based classification framework. The included studies evaluated purified compounds, crude extracts, essential oils, formulations, and combination treatments. Despite chemical diversity, antitumoral activity converged on defined biological processes, including apoptosis, non-apoptotic regulated cell death, redox modulation, oncogenic signaling inhibition, cell-cycle arrest, epigenetic regulation, photodynamic ROS generation, and chemopreventive or immune-mediated mechanisms. Mechanistic specificity was higher among purified compounds, while complex extracts showed broader, context-dependent effects. Several agents demonstrated consistent in vitro and in vivo activity, which supports their translational relevance. Natural compounds target shared biological vulnerabilities in cSCC through mechanistically convergent pathways. The framework presented here supports mechanism-guided prioritization and may facilitate the translation of promising compounds into clinically relevant strategies. Full article