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UV generates oxidative free radicals. UV photons interact with atomic oxygen to promote formation of free radical derivatives such as superoxide, hydrogen peroxide and the highly reactive hydroxyl radical. Free radicals avidly attack macromolecules such as protein, lipid, RNA and DNA, altering their structure and interfering with their function. Detoxifying and protective enzymes such as superoxide dismutase, catalase and glutathione peroxidase detoxify and reduce levels of oxidative species in the cell.
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UV radiation (UV) is classified as a "complete carcinogen" because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV...
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... with epidermal hyperkeratosis is adaptive melanization of the skin, also known as tanning [4,10,83 – 86]. UV up-regulates production and epidermal accumulation of melanin pigment in the skin [87 – 91]. This important physiologic response protects the skin against subsequent UV damage, and defects in this pathway are linked with cancer susceptibility. UV-mediated skin darkening is actually biphasic, with initial skin darkening occurring from redistribution and/or molecular changes to existing epidermal melanin pigments. Delayed increases in skin darkening, mediated by actual up-regulation in melanin synthesis and transfer to keratinocytes, begin several h to days after UV exposure [92,93]. Adaptive melanization is likely a complex physiologic response [4,10,83,85] involving multiple skin cell types interacting in a variety of ways ( Figure 4) [86,94 – 102]. UV has many other effects on the skin, including induction of an immune-tolerant or immunosuppressive state [103 – 110] and production of vitamin D by direct conversion of 7-dehydrocholesterol into vitamin D 3 (cholecalciferol) [61 – 69]. Ambient sunlight, for the most part, is a mixture of UVA and UVB, yet each UV component may exert different and distinct effects on the skin [111,112]. UVB, for example, is a potent stimulator of inflammation and the formation of DNA photolesions (such as mutagenic thymine dimers) [112,113], whereas UVA is much less active in these measures but instead is a potent driver of oxidative free radical damage to DNA and other macromolecules [114 – 116]. Thus, each may contribute to carcinogenesis through different mechanisms [117 – 119]. The influence of UVA and UVB on skin physiology is an active area of investigation. Besides promoting formation of photodimers in the genome, UV causes mutations by generating reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide and the hydroxyl radical [21] (Figure 5). Nucleotides are highly susceptible to free radical injury. Oxidation of nucleotide bases promotes mispairing outside of normal Watson-Crick parameters, causing mutagenesis [120]. The transversion guanine→thymine, for example, is a well -characterized mutation caused by ROS by oxidizing guanine at the 8th position to produce 8-hydroxy-2'-deoxyguanine (8-OHdG) [121,122]. 8-OHdG tends to pair with an adenine instead of cytosine and therefore this oxidative change mutates a G/C pair into an A/T pair. Such mutations can be found in tumors isolated from the skin, suggesting that oxidative injury can be carcinogenic [123]. Cellular maintenance pathways exist to inactivate oxidative species as well as to repair the DNA damage they cause. The base excision repair pathway (BER) is the main molecular means by which cells reverse free radical damage in DNA to avoid oxidative mutagenesis. This pathway is initiated by damage-specific glycosylases that scan DNA for specific alterations including deaminated, alkylated or oxidized bases. After altered or inappropriate bases are recognized by a lesion-specific glycosylase, the enzyme cleaves the nucleotide base from the sugar and phosphodiesterase backbone by lysis of the N -glycosylic bond between the base and the deoxyribose. This step forms an abasic or apurinic/apyrimidinic (AP) site in the DNA, which is then processed and repaired using the complementary strand as a template to ensure fidelity. Cells also have a complex and robust network of anti-oxidant molecules that detoxify reactive species to prevent free radical changes to DNA and other macromolecules. Glutathione (GSH) is an oligopeptide made up of three amino acids- cysteine, glycine and glutamine and is among the ...
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p class="abstract"> Background: Worldwide, skin cancer is a major public health concern. It is a common malignancy in Saudi Arabia. The three most prevalent types of skin cancer are basal cell carcinoma, squamous cell carcinoma and melanoma. Exposure to ultraviolet (UV) radiation is the most common modifiable risk factor to lower the risk of the le...
Citations
... (Hussen et al., 2024b;Rhie et al., 2001;Irato and Santovito, 2021) Melanogenesis ROS imbalance can affect melanin production, leading to pigmentation disorders UV-induced ROS and RNS can stimulate skin melanogenesis, a melanin production process, leading to dermatological issues like melasma, hyperpigmentation, and actinic lentigo due to abnormal melanin production (Uwa, 2017;Ö zkan et al., 2005;Darvin et al., 2006;Rattanawiwatpong et al., 2020;Glynn et al., 2007;Kamei et al., 2009;Trela-Makowej et al., 2022) Skin Matrix ROS promote the breakdown of collagen and elastin in the dermis ROS trigger growth factors and cytokines, causing collagen degradation and inflammatory cytokines, attracting neutrophils, monocytes, and macrophages, contributing to skin aging and increased ROS production (Pinnell, 2003;Santos et al., 2021;Al-Niaimi and Chiang, 2017;Ohshima et al., 2009;Chambial et al., 2013;Ernster and Dallner, 1995;Aaseth et al., 2021;Ayunin et al., 2022;Mortensen et al., 1997;Du et al., 2017) olive or light brown. Type V is brown skin that rarely burns and tans profusely (D'Orazio et al., 2013). The differences between these skin types are primarily based on their inherent melanin content and their responses to UV radiation. ...
... UV radiation has lots of damaging effects on the skin. UV radiation induces skin redness, intracellular inflammation, programmed cell death [13,45,46], cellular senescence [47,48], and ultimately skin cancer [49]. UVA radiation, especially, through the production of ROS, can cause cellular DNA damage, inflammatory responses, and collagen degradation, ultimately leading to skin aging and wrinkles [16,50,51]. ...
... In fact, one of the most common causes is the over exposure of skin to ultraviolet radiations coming from the sun [2]. The dangers of UV rays are greater in fair-skinned people who are sensitive to the sun than in people with dark skin who are less sensitive to the sun [42]. This disease is more common in geographical areas such as Australia, where there is a lot of sunlight, and most people have fair skin. ...
Background
Melanoma is a highly aggressive skin cancer, where early and accurate diagnosis is crucial to improve patient outcomes. Dermoscopy, a non-invasive imaging technique, aids in melanoma detection but can be limited by subjective interpretation. Recently, machine learning and deep learning techniques have shown promise in enhancing diagnostic precision by automating the analysis of dermoscopy images.
Methods
This systematic review examines recent advancements in machine learning (ML) and deep learning (DL) applications for melanoma diagnosis and prognosis using dermoscopy images. We conducted a thorough search across multiple databases, ultimately reviewing 34 studies published between 2016 and 2024. The review covers a range of model architectures, including DenseNet and ResNet, and discusses datasets, methodologies, and evaluation metrics used to validate model performance.
Results
Our results highlight that certain deep learning architectures, such as DenseNet and DCNN demonstrated outstanding performance, achieving over 95% accuracy on the HAM10000, ISIC and other datasets for melanoma detection from dermoscopy images. The review provides insights into the strengths, limitations, and future research directions of machine learning and deep learning methods in melanoma diagnosis and prognosis. It emphasizes the challenges related to data diversity, model interpretability, and computational resource requirements.
Conclusion
This review underscores the potential of machine learning and deep learning methods to transform melanoma diagnosis through improved diagnostic accuracy and efficiency. Future research should focus on creating accessible, large datasets and enhancing model interpretability to increase clinical applicability. By addressing these areas, machine learning and deep learning models could play a central role in advancing melanoma diagnosis and patient care.
... As a major skin stressor, UV radiation leads to a variety of skin lesions [27] but also produces vitamin D [28], has local and systemic immunosuppressive effects [29], and stimulates melanin production [30]. Exposure to acute or chronic UV radiation and elevated levels of ROS are major contributors to the development of a variety of skin diseases, including skin cancer, skin aging, and dermatitis [31,32]. However, little is known about how acute UV radiation affects melanin synthesis in the epidermis. ...
The aim of this study was to investigate how ultraviolet B (UVB) light regulates AP-1 expression via the β2-adrenergic receptor (β2-AR) in epidermal keratinocytes, which in turn regulates melanin synthesis in melanocytes, thereby modulating downstream melanin production in skin hair follicles and altering mouse skin color. We established a UV-irradiated mouse model to investigate the effects of UV radiation on changes in skin color. By measuring changes in the expression of genes related to cutaneous sympathetic nerves, norepinephrine synthesis and melanin synthesis, we investigated the relationship between β2-AR expression and cutaneous melanogenesis and determined the localization of β2-AR in cells. The results of the siRNA-mediated transfection of keratinized cells with downregulated β2-AR expression were further verified in vitro. Our results suggest that UVB alters the color of the dorsal skin in mice by activating the AP-1/IL-6 pathway, which triggers the sympathetic release of norepinephrine, thereby increasing β2-AR expression in keratinocytes. Overall, our study improves the current understanding of how UVB light influences skin color changes and highlights the complex interplay between ultraviolet radiation and skin physiology.
... The incidence of melanoma is higher in the fair-skinned population [4], as the levels of melanin pigment, which protects against UV radiation, are low [5,6]. Additionally, melanoma metastasizes more easily than other types of skin cancer and can quickly become fatal [7]. ...
Background: Melanoma is the most aggressive and lethal skin cancer that affects thousands of people worldwide. Ruthenium complexes have shown promising results as cancer chemotherapeutics, offering several advantages over platinum drugs, such as potent efficacy, low toxicity, and less drug resistance. Additionally, anthraquinone derivatives have broad therapeutic applications, including melanoma. Objectives: Thus, two new ruthenium complexes with 1-hydroxy-9,10-anthraquinone were obtained: trans-[Ru(HQ)(PPh3)2(bipy)]PF6 (1) and cis-[RuCl2(HQ)(dppb)] (2), where HQ = 1-hydroxy-9,10-anthraquinone, PPh3 = triphenylphospine, bipy = 2,2′-bipyridine, PF6 = hexafluorophosphate, and dppb = 1,4-bis(diphenylphosphine)butane. Methods: The complexes were characterized by infrared (IR), UV–vis, 1H, 13C{1H}, and 31P{1H} NMR spectroscopies, molar conductivity, cyclic voltammetry, and elemental analysis. Furthermore, density functional theory (DFT) calculations were performed. Results: Compound (2) was determined by single-crystal X-ray diffraction, which confirms the bidentate coordination mode of HQ through the carbonyl and phenolate oxygens. Additionally, DNA-binding experiments yielded constants of 105 M−1 (Kb = 6.93 × 105 for (1) and 1.60 × 105 for (2)) and demonstrate that both complexes can interact with DNA through intercalation, electrostatic attraction, or hydrogen bonding. Conclusions: The cytotoxicity profiles of the compounds were evaluated in human melanoma cell lines (SK-MEL-147, CHL-1, and WM1366), revealing greater cytotoxic activity for (1) on the CHL-1 cell line with an IC50 of 14.50 ± 1.09 µM. Subsequent studies showed that (1) inhibits the proliferation of CHL-1 cells and induces apoptosis, associated at least in part with the pro-oxidant effect and cell cycle arrest at the G1/S transition.
... UV-A, which constitutes 90-95% of the UV radiation reaching the Earth's surface, is the predominant form and responsible for skin aging. Its longer wavelength (320-400 nm) allows it to penetrate deeply into the dermis layer, generating ROS that can damage DNA (D'Orazio et al. 2013). Quercetin also notably protected HaCaT cells from UV-B and UV-C radiation, as well as from the irritant sodium persulfate by significantly increasing cell viability (SMD, 1.43, 95% CI, 0.22 to 2.64, P = 0.02, Z score = 2.31, Fig. 9.B). ...
... Although UV-B and UV-C radiation are more harmful than UV-A, their presence at the Earth's surface is limited, with UV-B accounting for 5-10% of UV radiation and UV-C being entirely absorbed by the ozone layer. UV-B primarily penetrates the epidermis, with a small portion reaching the dermis and it directly promotes DNA mutations and skin cancers (D'Orazio et al. 2013). Our results demonstrated that quercetin effectively protected skin-related cells in both the epidermis and dermis layers from various UV radiation components. ...
Quercetin is abundant in plants and has notable pharmacological properties for skin health. This review aims to comprehensively evaluate the effects of quercetin on skin-related issues, adhering to the PRISMA guidelines and analyzing studies from ScienceDirect, Web of Science, Scopus, and PubMed. Of the 1,398 studies identified, 65 studies met the criteria for meta-analysis. The meta-analysis indicated that quercetin had powerful antioxidant properties, protecting against oxidative stress by significantly lowering levels of MDA (Z-score, 2.51), ROS (Z-score, 3.81), and LPO (Z-score, 4.46), and enhancing enzymes of GSH (Z-score, 5.46), CAT (Z-score, 5.20), and SOD (Z-score, 4.37). Quercetin acted as an anti-inflammatory by significantly suppressing protein regulators such as NF-κβ, AP-1, and MAPKs (ERK and JNK), cytokines of TNFα, IL-6, IL-1β, IL-8, and MCP-1, and enzymes of COX-2, iNOS, and MPO, while upregulating the cytokine IL-10. Additionally, quercetin significantly suppressed IL-4 (Z-score, 3.16) and IFNγ (Z-score, 3.76) cytokines involved in chronic inflammation of atopic dermatitis. Quercetin also supported wound healing by significantly decreasing inflammatory cells (Z-score, 5.60) and enhancing fibroblast distribution (Z-score, 5.98), epithelialization (Z-score, 8.57), collagen production (Z-score, 4.20), and angiogenesis factors of MVD (Z-score, 5.66) and VEGF (Z-score, 3.86). Furthermore, quercetin significantly inhibited tyrosinase activity (Z-score, 1.95), resulting in a significantly reduced melanin content (Z-score, 2.56). A significant reduction in DNA damage (Z-score, 3.27), melanoma cell viability (Z-score, 2.97), and tumor formation was also observed to ensure the promising activity of quercetin for skin issues. This review highlights quercetin's potential as a multifaceted agent in skin care and treatment.
Graphical abstract
... (22) UVB irradiation induces keratinocyte proliferation and its accumulation in the epidermis, which results in an increased in epidermis thickness. (23) In addition, its depleted collagen content and deposition. This event can be caused by the increased production and activities of collagen degrading enzymes or protein that contribute to collagen deposition by cells that located in the skin i.e., neutrophil, macrophage, mast cells, and fibroblast. ...
BACKGROUND: Ultraviolet B (UVB) radiation is commonly known to be related to skin inflammation. The inflammation process is orchestrated by many cell types, including immune cells. Changes in bone marrow cellularity can also be an indicator of inflammation. Megakaryocytes, myeloid immune cells progenitor and erythroid progenitor cells, are at high risk of changes upon UVB irradiation. However, there are still limited study observing the change of bone marrow cell population after UVB irradiation. Therefore, this study was conducted to investigate the alteration of the skins, emperipolesis, and the change in erythroid and myeloid cell population in bone marrow after UVB irradiation.METHODS: Ten Wistar rats were divided equally into control and UVB-irradiated group. The skin superficial condition before and after UVB irradiation was observed with a skin analyzer camera. On the 9th day, skin tissues were processed for the observation of general skin structure with hematoxylin-eosin (HE) staining, mast cells infiltration with toluidine blue staining, and collagen fibers with Mallory staining. Bone marrow and peripheral blood samples were collected and proceeded for Giemsa-staining to observe the cell population.RESULTS: Erythema appeared on the skin as marked by orange-red spots. There were hyperkeratosis and pigment accumulations in the skin of UVB-irradiated group. The depletion of collagen-density and hemorrhage were clearly observed in the skin of UVB-irradiated group. There were higher mast cell numbers in the UVB-irradiated skin compared to non-treated skin. The erythroid-to-myeloid ratio in the bone marrow was decreased to around 1.6:11.2 from the normal ratio of 1:4. In addition, emperipolesis was observed in the bone marrow induces by UVB-irradiation.CONCLUSION: These results indicate that UVB-irradiation alters the skin structure, erythroid-to-myeloid ratio, and induced emperipolesis.KEYWORDS: emperipolesis, erythroid, myeloid, skin, UVB radiation
... It is responsible for the protection of the body from external factors, such as air pollution, toxic chemicals, pathogenic microorganisms, or ultraviolet (UV) radiation [1]. The frequency of exposure to the sun can trigger oxidative stress and inflammation or lead to cell damage or tumor formation [2]. One of the defense mechanisms of the body against UV radiation is the production of the dark pigment melanin [3,4]. ...
Tyrosinase is a key enzyme responsible for the formation of melanin (a natural skin pigment with ultraviolet-protection properties). However, some people experience melanin overproduction, so new, safe, and biocompatible enzyme inhibitors are sought. New tripeptide tyrosinase inhibitors were developed using molecular modeling. A combinatorial library of tripeptides was prepared and docked to the mushroom tyrosinase crystal structure and investigated with molecular dynamics. Based on the results of calculations and expert knowledge, the three potentially most active pep-tides (CSF, CSN, CVL) were selected. Their in vitro properties were examined, and they achieved half-maximal inhibitory concentration (IC 50) values of 136.04, 177.74, and 261.79 µM, respectively. These compounds attach to the binding pocket of tyrosinase mainly through hydrogen bonds and salt bridges. Molecular dynamics simulations demonstrated the stability of the peptid-tyrosinase complexes and highlighted the persistence of key interactions throughout the simulation period. The ability of these peptides to complex copper ions was also confirmed. The CSF peptide showed the highest chelating activity with copper. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed that none of the test tripeptides showed cytotoxicity toward the reconstructed human epidermis. Our results indicated that the developed tripeptides were non-toxic and effective tyrosinase inhibitors. They could be applied as raw materials in skin-brightening or anti-aging cosmetic products.
... The skin, as the largest organ of the human body, is densely populated with nerve endings, making it highly sensitive to various external stimuli, including physical, chemical, and biological factors [1][2][3]. Sunburn is an acute inflammatory reaction caused by excessive exposure to ultraviolet (UV) radiation, also referred to as an oxidative stress response [4,5]. Its primary symptoms include redness, swelling, heat, and pain in the affected areas, causing significant discomfort for patients. ...
An excess of reactive oxygen species (ROS), leading to oxidative stress, is a major factor in aging. Antioxidant therapies are considered crucial for delaying aging. Nanoceria, a nanozyme with antioxidant activity, holds significant potential in protecting cells from oxidative stress-induced damage. This research examines the neuroprotective role of nanoceria on HT22 cells subjected to oxidative stress induced by hydrogen peroxide (H2O2) and explores the associated molecular mechanisms. Our findings indicate that nanoceria enhances bcl-2 expression and significantly reduces Bax expression, resulting in an increased bcl-2/Bax ratio, which confirms its anti-apoptotic effect. Nanoceria boosts catalase expression and suppresses the p38 MAPK signaling pathway, indicating its role in shielding HT22 cells from oxidative stress damage induced by H2O2 through various protective mechanisms. These findings provide crucial experimental evidence for the potential applications of nanoceria in skin anti-aging and the prevention and treatment of other oxidative stress-related diseases.
... The alteration of global climate, particularly due to the depletion of stratospheric ozone, results in an increase in environmental UVR, which is a significant contributor to skin damage and tumorigenesis. Skin cancer comprises three common types: basal cell carcinoma, squamous cell carcinoma, and malignant melanoma [33,34]. It has become crucial to find effective measures for preventing the development of skin cancer. ...
Green tea catechins (GTCs) are a group of bioactive polyphenolic compounds found in fresh tea leaves (Camellia sinensis (L.) O. Kuntze). They have garnered significant attention due to their diverse health benefits and potential therapeutic applications, including as antioxidant and sunscreen agents. Human skin serves as the primary barrier against various external aggressors, including pathogens, pollutants, and harmful ultraviolet radiation (UVR). Skin aging is a complex biological process influenced by intrinsic factors such as genetics and hormonal changes, as well as extrinsic factors like environmental stressors, among which UVR plays a pivotal role in accelerating skin aging and contributing to various dermatological conditions. Research has demonstrated that GTCs possess potent antioxidant properties that help neutralize free radicals generated by oxidative stress. This action not only mitigates cellular damage but also supports the repair mechanisms inherent in human skin. Furthermore, GTCs exhibit anti-carcinogenic effects by inhibiting pathways involved in tumor promotion and progression. GTCs have been shown to exert anti-inflammatory effects through modulation of inflammatory signaling pathways. Chronic inflammation is known to contribute significantly to both premature aging and various dermatological diseases such as psoriasis or eczema. By regulating these pathways effectively, GTCs may alleviate symptoms associated with inflammatory conditions. GTCs can enhance wound healing processes by stimulating angiogenesis. They also facilitate DNA repair mechanisms within dermal fibroblasts exposed to damaging agents. The photoprotective properties attributed to GTCs further underscore their relevance in skincare formulations aimed at preventing sun-induced damage. Their ability to screen UV light helps shield underlying tissues from harmful rays. This review paper aims to comprehensively examine the beneficial effects of GTCs on skin health through an analysis encompassing in vivo and in vitro studies alongside insights into molecular mechanisms underpinning these effects. Such knowledge could pave the way for the development of innovative strategies focused on harnessing natural compounds like GTCs for improved skincare solutions tailored to combat environmental stresses faced by the human epidermis.
