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We previously reported endogenous activation of the DNA damage response (DDR) in the epidermis surrounding basal cell carcinoma resected from Nagasaki atomic bomb survivors, suggesting the presence of genomic instability (GIN) in the survivors as a late effect of radiation. Dual-color immunofluorescence (IF) analysis of TP53-binding protein-1 (53BP1) and a proliferative indicator, Ki-67, to elucidate GIN in tumor tissues revealed that abnormal 53BP1 expression is closely associated with carcinogenesis in several organs. The present study aimed to confirm the presence of radiation-induced GIN in the non-neoplastic epidermis of patients with radiation-induced skin cancer. Formalin-fixed paraffin-embedded tissues were obtained from all participants between 2008 and 2019 at the Nagasaki University Hospital. 53BP1 nuclear expression was examined using dual-color IF analysis with Ki-67 expression to assess the extent and integrity of the DDR. Expressions of gamma-H2AX, p53 and p21 were also analyzed using the dual-color IF analysis for their association with 53BP1. The results of this study provide evidence for sporadic activation of the DDR in medically irradiated and ultraviolet-exposed epidermis as a long-lasting radiation effect, which is a predisposition to skin cancer. Furthermore, the incidence of abnormal 53BP1 expression in cancer cells was higher than in non-neoplastic epidermal cells surrounding cancer, suggesting a correlation between the type of 53BP1 and the malignant potential of skin tumors. This study highlights the usefulness of dual-color IF for 53BP1 (and Ki-67) as an indicator to estimate the level of GIN as a long-lasting health effect of radiation exposure., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Aluminum (Al) may be beneficial to crops, but in excess becomes detrimental to the germination and initial development of seedlings. The main determining indicators are the type of crop and exposure duration. The aim of this study was to examine the influence of Al and of UV-C light on the germination and initial growth of white oats. Seeds were sown on germitest paper in a solution of 100, 200, 300, 400, or 500 mg/L of aluminum chloride and kept in a germination chamber at 20°C for a 12-hr photoperiod. Germination and seedling growth parameters were determined after 5 and 10 days. The seeds were also exposed to two doses of UV-C (0.85 and 3.42 kJ m -2 ) under aluminum chloride stress (200 mg/L). Data demonstrated that treatment with aluminum chloride significantly decrease in germination at 200 mg/L and total seedling length at 100 mg/L. Exposure of seeds to UV-C light under excess Al (200 mg/L) did not show a significant effect on germination and growth compared to control (non-irradiated). Results indicated that exposure to high concentration of Al in the medium adversely altered germination and initial growth of white oat seedlings. Although UV-C light alone was not detrimental to the germination process, treatment with UV-C light also failed to mitigate the toxic effects of Al.

Solar radiation is the main source of human exposure to UV rays, which is the major carcinogen in skin cancers by inducing DNA damage. Skin cells repair these damages by activating the DNA damage response (DDR) to safeguard genome integrity, thereby preventing skin cancers. Peroxisome proliferator-activated receptor beta (PPARβ), a druggable transcription factor, is involved in the development of UV-dependent skin cancers, although its role is not mechanistically elucidated. We showed previously that PPARβ knockout (KO) mice are less prone to UV-induced skin cancers. Here, we report that PPARβ directly regulates gene expression programs associated with cell cycle and DNA repair pathways in normal human epidermal keratinocytes (NHEK). The loss of function of PPARβ in human keratinocytes led to a downregulation in the expression of key cell cycle regulators, including cyclins and cyclin-dependent kinases (CDKs). Simultaneously, it upregulated the expression of p21 protein, a known CDK inhibitor. These molecular alterations resulted in a significant reduction in cell proliferation and induced cell cycle arrest at the G2/M phase. Moreover, the absence of functional PPARβ disrupted the expression and activation of the ataxia telangiectasia and Rad3-related (ATR) pathway, a critical component of the cellular response to UV-induced DNA damage. The alterations in the ATR pathway likely contributed to an increased apoptotic response of NHEK to UV radiation. Using a mouse melanoma model, we demonstrated that the depletion of PPARβ decreases tumorigenicity of melanoma cells and delays tumor formation. Our data suggest that PPARβ inhibition could be considered as a therapeutic target for the prevention of UV-induced skin cancers, by regulating cell proliferation, attenuating DDR, and eliminating skin cells with high UV-induced mutational burden., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Allicin is a sulfide extracted from garlic bulbs responsible for various physiological and pathophysiological effects, including antioxidant, antibacterial, and anti-parasite activities. However, its efficacy and mechanism of protecting UVB-induced photodamage have not been studied. The research explores Allicin's protective roles and underlying mechanisms in UVB-induced photodamage of keratinocytes. UVB was employed to generate photodamage in the HaCaT cell line. DCFH-DA fluorescent and Biochemical analyses were carried out to evaluate reactive oxygen species (ROS) and oxidative stress on UVB-induced photodamage to HaCaT cells. RT-qPCR and western blot were performed to measure mRNA and protein expression. Allicin pretreatment (10 and 25 µM) improved cell proliferation and reduced apoptotic rates in UVB-induced HaCaT cells. Allicin (10 and 25 µM) inhibited tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) expressions (all, P < 0.001). Allicin reduced the intracellular ROS level and attenuated oxidative stress, with reduced malondialdehyde (MDA) level while increasing the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSh-Px) (all, P < 0.001) in UVB-induced HaCaT cells. Allicin pretreatment inhibited autophagy and reduced the protein expression of Beclin-1 while increasing the p62 protein expression (all, P < 0.001). We also observed that Allicin pretreatment reduced the NLRP3-related protein, such as Caspase-1 (P < 0.001) and increased the protein expressions of the PI3K/Akt pathway molecules, such as PI3K and Akt (all, P < 0.001). Our research data demonstrated that Allicin might inhibit UVB-induced photodamage of keratinocytes via inhibiting NLRP3 inflammasomes and activating the PI3K/Akt pathway., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. The authors report no conflict of interest. Ethical approval Ethical approval is not required for this study in accordance with local or national guidelines., (© 2024. The Author(s).)

The association between psoriasis and non-melanoma skin cancer (NMSC) remains inconsistent despite biologic plausibility. Immunosuppressive effects of systemic psoriasis treatments have also been hypothesized to contribute to the development of NMSC as well. However, data assessing the risk of NMSC associated with immunomodulatory psoriasis medications, particularly newer biologic therapies, are limited.Our objective was to quantify the association between psoriasis, systemic psoriasis therapy, and NMSC accounting for other relevant factors such as smoking status and ultraviolet (UV) light exposure.We performed a cross-sectional, case-control study of 413,457 adults containing 7,478 psoriasis and 9,756 NMSC cases taken from the National Institutes of Health All of Us Research Program database (queried July 2024). NMSC, psoriasis, UV-light exposure, and drug exposures were defined using disease or drug classification codes. Smoking exposure was defined using survey data. Multivariable logistic regression models were used to assess relationships, providing adjusted odds ratios with 95% confidence intervals (aOR with 95% CI).After adjustment for UV-light exposure, coal tar exposure, smoking status, race, ethnicity, gender, age, income, and insurance status, psoriasis history was a significant predictor for NMSC (aOR 1.37 95% CI 1.22-1.52). Psoriasis patients exposed to immunomodulatory medications were also at higher odds of NMSC compared to psoriasis patients who were never exposed (aOR 1.26 95% CI 1.01-1.57). Of these drugs, IL-23 inhibitors (aOR 2.47 95% CI 1.17-5.18), Janus kinase inhibitors (aOR 2.32 95% CI 1.09-4.92), and azathioprine (aOR 2.16 95% CI 1.18-3.96) were the only classes that significantly contributed to increased NMSC risk in psoriasis patients.Psoriasis is independently associated with NMSC. While treatment with some classes of systemic medications is also associated with increased NMSC risk, therapeutic benefits are significant and should be weighed against this risk. NMSC is treatable and high-risk patients may benefit from increased surveillance or preventative counseling. Further prospective studies that assess medication dose and length of exposure should validate our findings., Competing Interests: Declarations. Ethics statement: This study was considered by the Baylor College of Medicine IRB to be nonhuman research and exempt from review. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Tight junction abnormalities are a common feature of inflammatory skin diseases such as psoriasis and atopic dermatitis and contribute to systemic immune responses. Evidence provided to date suggests that Heat shock protein 105 kDa (HSP105) exhibits significant protective effects in response to destructive external stimuli. However, its role in UV-induced skin tight junction remains to be fully understood., Objective: To investigate the role and underlying mechanisms of HSP105 in acute UVB-induced tight junction damage., Methods: By utilizing bioinformatics analysis, together with an in vitro UVB-induced tight junction injury model in HaCaT cells, we investigated the expression and localization of HSP105 and the tight junction proteins CLDN1, CLDN4, and OCLN. The role of HSP105 was further explored through shRNA-mediated silencing and lentiviral overexpression in HaCaT cells. Potential pathways by which HSP105 regulates tight junction were analyzed using the GSEA algorithm and validated through in vitro experiments., Results: Acute UVB irradiation mainly disrupted the distribution of CLDN1, CLDN4, and OCLN in HaCaT cells, while gene expression remained largely unaffected. Acute UVB irradiation also caused a reduction in HSP105 protein levels in HaCaT cells. Inhibition of HSP105 expression worsened tight junction fragmentation. GSEA analysis showed that Store-operated calcium entry (SOCE) was significantly correlated with HSP105 expression. Silencing HSP105 downregulated STIM1 transcription and inhibited SOCE, leading to further fragmentation of tight junction proteins. Overexpression of HSP105 partially mitigated the damage to tight junction integrity caused by UVB and SOCE inhibition., Conclusion: HSP105 protects against acute UVB-induced tight junction damage through the regulation of SOCE. Our findings offer new insights into the treatment of skin barrier injury., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A woman in her early 20s with progressive keratoconus underwent corneal collagen cross-linking using the sub400 protocol. The central 5.5 mm of the epithelium was removed after the application of 20% alcohol. Topical riboflavin 0.1% was applied every 3 min for 30 min and then irradiated with UV-A light (irradiance of 3 mW/cm 2 for 16 min). At the end of the procedure, a therapeutic contact lens was placed and ofloxacin 0.3% (4 times daily), dexamethasone 0.1% (4 times daily) and lubricant (hourly) drops were prescribed.Two days after the procedure, the patient presented with a painless red eye. A 360° peripheral ring-like infiltrate was observed in the 5.5 mm zone, consistent with a sterile infiltrate. Dexamethasone 0.1% drops were prescribed and tapered for 1 month. Although the infiltrate gradually decreased under corticosteroid therapy, the patient's condition worsened after discontinuation of treatment. Treatment was resumed and complete recovery was observed 4 months later., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Excessive exposure to ultraviolet radiation B (UVB) has been shown to contribute to the aging of human skin cells. Previous research has demonstrated that atorvastatin calcium (Ato) can mitigate the aging effects caused by chemotherapy drugs. However, it remains unclear whether Ato can alleviate skin aging induced by ultraviolet radiation. In this study, through in vitro experiments with Hacat cells, we found that Ato can significantly reduce the UVB-induced increased expression of age-related protein p16 and age-related gene p21, and also reduce the up-regulation of inflammatory factors such as IL-1 and IL-6. Besides, it can reduce the expression of metallomatrix protein (MMP1 and MMP9), and inhibit cell senescence and inflammatory damage. Similarly, we found that Ato can enhance skin collagen fiber reduction and collagen volume decrease, repair skin photoaging and damage induced by UVB rays, and speed up the rate at which the wounded location heals in vivo using Balb/c mice. In the mechanism, Ato markedly decreased the expression of p-p38, p-p65, p-mTOR in vivo and in vitro, suggesting that it may act on Mitogen-activated protein kinase (MAPK), Nuclear factor κB (NF- κB) and Mammalian target of rapamycin (mTOR) signaling pathways to produce above marked effects. In conclusion, Ato obviously relieved UVB-induced photoaging and damage, thus providing evidence for its potential in mitigating skin aging caused by ultraviolet radiation., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ultraviolet (UV) B irradiation is closely related to skin aging and skin damage. Here, we report the photoprotective mechanism of action of ginseng berry rare saponins (GFRS) on UVB-induced damage to human keratinocytes and mouse skin. Several UVB irradiation-induced cytotoxicity and oxidative stress responses were assessed. GFRS preconditioning significantly improved HaCaT cell survival and reduced the levels of the DNA damage markers histone H2AX and cyclobutane pyrimidine dimer. Under oxidative stress, GFRS could reduce the transformation and loss of the mitochondrial membrane potential to the monomer form; effectively clear the expression of lipid reactive oxygen species, malondialdehyde, and other peroxides, and restore total superoxide dismutase, glutathione peroxidase, and catalase levels. The occurrence of ferroptosis after UVB induction was also studied. Erastin exacerbated the induced cellular iron overload, whereas GFRS and Fer-1 reversed this response to varying degrees. Mechanistically, GFRS activated the Nrf2/HO-1/GPX4 pathway and inhibited the phenomenon of ferroptosis in cells. Our findings were confirmed using a mouse model of UV induced skin injury. GFRS not only mitigated lipid peroxides and iron overload in tissues but also prevented skin barrier damage and collagen loss. Therefore, GFRS shows potential as a novel functional product as it protects the skin from UVB light-induced damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Recently, the use of natural products as skin photoprotective agents has been in increasing demand. This study investigated the bioactivity of phycocyanin (PC) extracted from Spirulina sp. on human skin fibroblast cell line (CCD-966SK), specifically focusing on apoptosis, necrosis, anti-inflammatory effects, and enzymatic reactions., Methods: The first step of this study was cyanobacterial cell culture and the extraction and purification of PC. After that, CCD-966SK cell line was cultivated under normal and UV irradiation. The bioassays included the cytotoxicity measurement, cell viability assay, morphology determination, tumour necrosis factor-α and Interleukin 6 release assays, enzyme activity for superoxide dismutase and glutathione peroxidase as well as malondialdehyde content and the cell-free extract of cyanobacterial stains were assessed., Results: The cell viability results showed that as the concentration of the PC increased, the viability of CCD-966SK cell line was reduced, which suggested that the effect of PC on the growth of fibroblast cells was dose dependent. The morphological results indicated that presence of PC in the fibroblast cell culture medium led to a transformation in cell morphology from spindle-shaped to spherical. PC released anti-inflammatory IL-6 and TNF-a cytokines, indicating high inflammation resistance. Furthermore, the findings revealed that PC dramatically reduced the release of superoxide dismutase, glutathione peroxidase, and malondialdehyde from inflammatory cells, with the reduction being more apparent at increasing doses., Conclusions: In conclusion, the results indicated that PC inhibit the CCD-966SK cell line by membrane destructor, which led to the increase the leakage of cell constituent and increase enzymes activities.

Background: Addressing the increasing incidence of skin cancer among young adults is a priority. The objective of the Risk Information and Skin-cancer Education for Undergraduate Prevention (RISE-UP) study is to identify personalized intervention components to prevent sunburn, a clinically significant outcome highly associated with skin cancer, in college students., Methods: Guided by the Elaboration Likelihood Model, the study will use Multiphase Optimization Strategy (MOST) methodology to test three intervention components (ultraviolet photography, MC1R genetic testing, and action planning) each with two levels (yes v. no) in a full-factorial experiment to evaluate unique and combined effects of these components to improve outcomes over the longer-term, with seasonally timed follow-up. At-risk University of Utah students (N = 528) will be recruited. Eligibility criteria include self-reported sunburn or tanning in the past year, or not utilizing recommended sun protection. After baseline assessment, participants will be randomized to intervention group, stratified by sex. Assessments will be completed at (1) Baseline; (2) Intervention; (3) 1 month after intervention; (4) 4 months after intervention (the end of the first summer); and (5) 15 months after intervention (the end of the second summer). The primary outcome will be participants' self-reported number of sunburns. Secondary outcomes will include self-reported sun protection and tanning behaviors and, in a randomly selected subgroup, an objective measure of ultraviolet radiation (UVR) exposure., Conclusion: The RISE-UP study will determine the efficacy of different combinations of personalized skin cancer preventative interventions for young adults and determine the optimal combination of intervention components to prevent skin cancer., Clinical Trial Registration: NCT05634252., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ultraviolet (UV) exposure triggers skin aging primarily by disrupting skin barrier function, resulting in dry skin and wrinkle formation. Oyster hydrolysate (OH), as a functional food, has been reported for anti-cancer, anti-oxidant and anti-apoptotic effects. This study investigated the underlying mechanism of OH effect on UVB-induced skin aging in SKH1 hairless mice. Mice were exposed to UVB three times per week while they were fed with a normal diet or diet containing OH for 10 weeks. Additionally, a randomized, double-blind, and placebo-controlled clinical trial was performed to investigate the OH effect on human skin moisturizing to evaluate its efficacy and safety. UVB exposure increased parameters of skin aging; dehydration, transepidermal water loss, and macroscopic dorsal skin lesions. OH significantly reduced these features of skin aging. Histological analysis demonstrated that OH decreased skin epidermal and dermal thickness and collagen degradation induced by UVB. OH significantly reduced ROS production, suppressed macrophage activation and neutrophil infiltration, and downregulated pro-inflammatory cytokine production. OH improved skin barrier function by increasing the expression of filaggrin, aquaporin-3, and hyaluronic acid synthesis enzymes and promoting recovery from skin damage. Importantly, the results from a human clinical trial demonstrated that OH improved skin moisturization and integrity with no side effects. Taken together, OH supplementation ameliorates skin damage via anti-oxidant and anti-inflammatory properties and enhances skin hydration and barrier function. OH has a therapeutic potential for skin photoaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Solar dermatitis (SD) is an acute, damaging inflammation of the skin caused by UV exposure, especially UVB. Therefore, the discovery of novel anti-SD therapeutic agents is crucial. Andrographis paniculata (AP) is a medicinal plant with a wide range of pharmacological effects. Increased evidence shows that AP has potential therapeutic effects on SD. However, the therapeutic mechanisms of AP against SD have not yet been completely elucidated, which is an unexplored field., Purpose: This study employed network pharmacology, molecular docking and experimental verification to ascertain the active constituents, possible targets, and biological pathways associated with AP in the treatment of SD., Methods: AP-related active ingredients and their potential targets were screened from TCMSP and Swiss Target Prediction database, respectively. Potential therapeutic targets of SD were collected using the GeneCards, DrugBank and OMIM databases. Then, we established protein-protein interaction (PPI), compound-target-disease (D-C-T-D) through Cytoscape to identify the major components, core targets of AP against SD. Next, the GO and KEGG pathway was identified by the David database of AP in the treatment of SD. Molecular docking techniques were used to estimate the binding force between the components and the hub genes. In this paper, we used UVB-irradiated HaCaT keratinocytes as an in vitro model and established the dorsal skin of UVB-irradiated ICR mice as an in vivo model to explore the mechanism for further verification., Results: There were 24 active components and 63 related target genes in AP against SD. PPI analysis showed that AKT-1, TNF-α, IL6, MMP9, EGFR, and PTGS2 shared the highest centrality among all target genes. KEGG pathway analysis revealed that the PI3K-Akt signaling pathway may be central in the anti-SD system. The molecular docking results showed that the main active components of AP have strong binding affinity with hub genes. In vitro results showed that WG had a protective effect on UVB-intervened HaCat cells. Western blot analysis showed that WG intervention achieved anti-inflammation by reducing the phosphorylated expression of AKT, PI3K proteins in the PI3K-AKT signaling pathway and downregulating the expression of TNF-α, IL-6, EGFR. Furthermore, Histological analysis confirmed that administration of WG to ICR mice significantly ameliorated UVB-induced skin roughness, epidermal thickening, disturbed collagen fiber alignment and wrinkles. Meanwhile, immunohistochemistry showed that administration of WG to ICR mice significantly reduced UVB-induced expression of MMP9, MPO, F4/80 in the skin. These results provide new insights into the contribution of WG to the development of clinical treatment modalities for UVB-induced SD., Conclusion: The crucial element in the fight against SD is WG, with the primary route being PI3K/Akt. The main components and hub genes had robust binding abilities. In vitro and vivo experiments showed that WG could inhibit the expression level of the hub genes by inhibiting the PI3K/Akt pathway. In summary, the information presented in this study indicates that WG might be utilised as a treatment for UVB-induced SD., Competing Interests: Declaration of competing interest The authors declare that there have no conflicts of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Ultraviolet (UV) irradiation of the skin causes mutations that can promote the development of melanoma and nonmelanoma skin cancer. High-dose UVB exposure triggers a vigorous skin reaction characterized by inflammation resulting in acute sunburn. This response includes the formation of sunburn cells and keratinocytes (KC) undergoing programmed cell death (apoptosis) when repair mechanisms of DNA damage are inadequate. The primary objective of this research was to clarify the involvement of Langerhans cells (LC) in the development of acute sunburn following intense UVB skin irradiation. To address this, we subjected the dorsal skin of mice to a single high-dose UVB exposure and analyzed the immediate immune response occurring within the skin tissue. Acute sunburn triggered an activation of LC, coinciding with a rapid influx of neutrophils that produced TNF-α. Furthermore, our investigation unveiled a marked increase in DNA-damaged KC and the subsequent induction of apoptosis in these cells. Importantly, we demonstrate a crucial link between the inflammatory cascade, the initiation of apoptosis in DNA-damaged KC, and the presence of LC in the skin. LC were observed to modulate the chemokine response in the skin following exposure to UVB, thereby affecting the trafficking of neutrophils. Skin lacking LC revealed diminished inflammation, contained fewer TNF-α-producing neutrophils, and due to the prevention of apoptosis induction, a lingering population of DNA-damaged KC, presumably carrying the risk of enduring genomic alterations. In summary, our results underscore the pivotal role of LC in preserving the homeostasis of UVB-irradiated skin. These findings contribute to a deeper understanding of the intricate mechanisms underlying acute sunburn responses and their implications for UV-induced skin cancer., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)

Background and Aims: Solar lentigo is a prevalent skin condition that affects a significant number of individuals. Fortunately, certain traditional Chinese medicines and monomers (TCMM) have proven effective in addressing these concerns. In this study, we evaluated the efficacy and underlying mechanism of TCMM, a combination of TCM and monomers in repairing solar lentigo., Methods: We detected and identified the main compounds of TCM using liquid chromatography-mass spectrometry (LC-MS) and through the approach of network pharmacology, we screened drug and disease targets, visualized networks with Cytoscape software, analyzed targets via Gene ontology and KEGG, clinically validated predictions. In a mouse model, UVB-induced pigmentation was assessed, and the effects of TCMM were evaluated. A clinical trial on 30 patients validated the depigmenting agent., Results: Active ingredients such as MSH, Butylated hydroxytoluen, Valerophenone, and Geranylacetone aid pigmentation treatment. One hundred and forty-three crore targets impact PI3K-Akt, MAPK signaling pathway, ect. pathways. TCMM reduced UVB-induced pigmentation, water loss, epidermal thickness, and melanin. It inhibited TYR, MITF, AKT1, VEGFA, PTGS2, TNF-α, IL-6, IL-1β. Clinical and microscopic analysis showed significant pigmentation reduction., Conclusions: The treatment of solar lentigo can benefit from the TCMM. By targeting multiple factors and pathways, this approach offers a comprehensive and effective treatment strategy., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: The aim of this study was to investigate the protective effect of quercetin loaded on solid lipid nanoparticles (SLN) in protecting human hair from ultraviolet-B (UV-B) light in vitro., Methods: In this study, solvent-emulsified diffusion method was used to fabricate nanoparticle formulations and then particle size, loading, and drug release tests were performed from different formulations. Variables include oily part proportion, liquid to solid oil part ratio, and surfactant to lipid ratio. The optimal formulation was prepared by examining the eight formulations and optimizing them. Six groups of hair with different treatments were exposed to UV light for 600 h and the changes were investigated by examining four factors: RMS (root mean square average, the microscopic profile peaks and valleys), peak to valley roughness, the amount of chemical changes by Fourier transform infrared spectroscopy (FTIR), and the amount of protein loss., Results: The selected formulation had a suitable particle size, loading percent, and release rate for penetration to hair. Quercetin-loaded SLN controlled RMS factor, peak to valley roughness, and reduced chemical changes and protein loss compared to other treatments., Conclusion: The optimize formulation showed positive effects in protecting the hair strands from UV-B radiation., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Though the exact causes of systemic lupus erythematosus (SLE) remain unknown, exposure to ultraviolet (UV) light is one of the few well-known triggers of cutaneous inflammation in SLE. However, the precise cell types which contribute to the early cutaneous inflammatory response in lupus, and the ways that UV dosing and interferons modulate these findings, have not been thoroughly dissected. Here, we explore these questions using the NZM2328 spontaneous murine model of lupus. In addition, we use iNZM mice, which share the NZM2328 background but harbor a whole-body knockout of the type I interferon (IFN) receptor, and wild-type BALB/c mice. 10-13-week-old female mice of each strain were treated with acute (300 mJ/cm 2 x1), chronic (100 mJ/cm 2 daily x5 days), or no UVB, and skin was harvested and processed for bulk RNA sequencing and flow cytometry. We identify that inflammatory pathways and gene signatures related to myeloid cells - namely neutrophils and monocyte-derived dendritic cells - are a shared feature of the acute and chronic UVB response in NZM skin greater than iNZM and wild-type skin. We also verify recruitment and activation of these cells by flow cytometry in both acutely and chronically irradiated NZM and WT mice and demonstrate that these processes are dependent on type I IFN signaling. Taken together, these data indicate a skewed IFN-driven inflammatory response to both acute and chronic UVB exposure in lupus-prone skin dominated by myeloid cells, suggesting both the importance of type I IFNs and myeloid cells as therapeutic targets for photosensitive patients and highlighting the risks of even moderate UV exposure in this patient population., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Skin aging is characterized by an imbalance between the generation and degradation of extracellular matrix molecules (ECM). Matrix metalloproteinases (MMPs) are the primary enzymes responsible for ECM breakdown. Intrinsic and extrinsic stimuli can induce different MMPs. However, there is limited literature especially on the summary of skin MMPs and potential inhibitors., Objective: We aim to focus on the upregulation of MMP expression or activity in skin cells following exposure to UV radiation. We also would like to offer valuable insights into potential clinical applications of MMP inhibitors for mitigating skin aging., Methods: This article presents the summary of prior research, which involved an extensive literature search across diverse academic databases including Web of Science and PubMed., Results: Our findings offer a comprehensive insight into the effects of MMPs on skin aging after UV irradiation, including their substrate preferences and distinct roles in this process. Additionally, a comprehensive list of natural plant and animal extracts, proteins, polypeptides, amino acids, as well as natural and synthetic compounds that serve as inhibitors for MMPs is compiled., Conclusion: Skin aging is a complex process influenced by environmental factors and MMPs. Research focuses on UV-induced skin damage and the formation of Advanced Glycosylation End Products (AGEs), leading to wrinkles and impaired functionality. Inhibiting MMPs is crucial for maintaining youthful skin. Natural sources of MMP inhibitor substances, such as extracts from plants and animals, offer a safer approach to obtain inhibitors through dietary supplements. Studying isolated active ingredients can contribute to developing targeted MMP inhibitors., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Accelerated pace of modern work and lifestyles subject individuals to various external and psychological stressors, which, in turn, can trigger additional stress through visible signs of fatigue, hair loss, and obesity. As the primary stress hormone affecting skin health, cortisol connects to the glucocorticoid receptor (GR) to aggravate skin issues induced by stress. This activation depends on the expression of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in skin cells, which locally converts cortisone-produced by the central and peripheral hypothalamic-pituitary-adrenal axis-into its active form., Methods: Our study delves deeper into stress's adverse effects on the skin, including the disruption of keratinocyte structural proteins, the loss of basement membrane proteins, and the degradation of collagen., Results: Remarkably, we discovered that Ectoin, an amino acid derivative obtained from halophilic bacteria, is capable of mitigating the inhibitory impacts of cortisone on the expression of cutaneous functional proteins, including involucrin, loricrin, laminin-5, and claudin-1. Moreover, Ectoin reduces the suppressive effect of stress on collagen and hyaluronic acid synthesis by impeding GR signal transduction. Additionally, Ectoin counterbalances the UVB-induced overexpression of 11β-HSD1, thereby diminishing the concentration of endogenous glucocorticoids., Conclusion: Our findings illuminate the significant potential of Ectoin as a preventative agent against stress-induced skin maladies., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Protection from solar ultraviolet radiation (UVR) is paramount in light-skinned pig breeds such as Yorkshire or Landrace to avoid sunburn., Objectives: Determination of the UVR exposure of a pig and the sun protection abilities of shade cloths with different shade rates., Animals: Life-sized plastic model of a Landrace pig., Materials and Methods: The model was equipped with 20 UVR meters at various anatomical positions that recorded the erythemal effective solar irradiance. A turntable enabled irradiation from different directions. Solar irradiance was measured in direct sunlight as well as under three shade cloths with different shade rates (50%, 75% and 90%) and a camouflage net. The sun protection factors (SPF) were determined as the ratio of unshaded-to-shaded measurements at the same solar elevation. The exposure ratio to ambient (ERTA) was calculated for each body site with respect to ambient irradiance. It allows determination of when pigs are at risk of sunburn and protection is needed., Results: The calculated ERTA values show that some body parts may receive higher values than ambient UVR. Measurements showed that the SPF of shade cloths depends on textile denseness. Selected shade cloths reached values of 3.5 (shade rate 50%), 4.2 (75%) and 5.8 (90%). Protection by the camouflage net was poor. The highest SPF was gained on body sides where ERTA was highest., Conclusions and Clinical Relevance: Shade cloths can protect all body sites effectively and vulnerable sites in particular. The results of our study enable an estimation of when pigs are at risk of sunburn and provide quantitative metrics for sun protection. This allows effective prevention of UVR-caused skin damage and secondary disorders., (© 2024 The Author(s). Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.)

The skin is the largest organ in the body and the only one to come into contact with solar UV radiation (UVR). UVA (320-400 nm) is a significant contributor to UV-related skin damage. The UVA spectrum makes up over 95% of solar-UV energy reaching the earth's surface causing the majority of the visible signs of skin photoaging. Many consumer products also emit UVA, including nail dryers. There have been sporadic reports suggesting that these units may be contributing to skin cancer incidence. This notion was recently bolstered by a finding that nail dryer-irradiated mammalian skin cells develop a mutational signature consistent with UVA exposure. This report was surprising considering the comparatively low level of UVA to which the skin is exposed during nail treatments. In this research, we investigated how UVA-emitting devices caused cytotoxic/genotoxic impact after only low levels of UVA exposure. Our data showed that levels of UVA in the unit are highly variable and location dependent. We confirm previous reports that using prolonged exposure protocols could induce significant levels of DNA damage. It was also determined that UV-induced DNA damage only partially correlated with the level of UVA fluency. On investigation, we found that the unit had a rapid increase in internal temperature when in use. Exposing human cells to these elevated temperatures acted synergistically with UVA to magnify the cytotoxic and genotoxic impact of UV irradiation., Competing Interests: Declaration of Conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Peter Sykora is the CSO and director of Amelia Technologies LLC. None of the entities involved in this research have any commercial interest now or in the future regarding UV-emitting nail devices.

Background: Ultraviolet radiation (UVR) exposure is the primary risk factor for melanoma, although the relationship is complex. Compared with radiation from UVB wavelengths, UVA makes up a majority of the surface solar UVR, penetrates the skin more deeply, is the principal range emitted by tanning beds, and is less filtered by sunscreens and window glass. Few studies have examined the relationship between ambient UVA and UVB and melanoma risk., Methods: Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated for the association between satellite-based ambient (based on residential history) UVA, UVB, and melanoma in non-Hispanic White participants using data from the United States Radiologic Technologists study, a large, nationwide prospective cohort. Associations of UVA and UVB quartile (Q) were examined in mutually adjusted and stratified models, additionally adjusted for demographic and sun sensitivity characteristics., Results: There were 837 incident melanoma cases among 62 785 participants. Incidence of melanoma was statistically significantly increased for the highest quartile of childhood UVA exposure after adjustment for UVB (IRR = 2.82; 95% CI = 1.46 to 5.44) but not for higher childhood UVB after adjustment for UVA. Childhood UVA was associated with increased melanoma risk within strata of UVB. Childhood UVB was not associated with melanoma after adjustment for UVA, but there was some evidence of lower risk with increased lifetime ambient UVB after UVA adjustment., Conclusions: Melanoma risk was elevated among participants living in locations with high annual childhood and lifetime UVA after controlling for UVB. With confirmation, these findings support increased protection from solar UVA for melanoma prevention., (Published by Oxford University Press 2024.)

The objective of this study was to examine the therapeutic efficacy of curcumin (CUR) and α-lipoic acid (ALA) in mitigating UV-A and UV-B-induced damage (UVAB) in rat dorsal skin. This was achieved through the utilisation of immunohistochemical (TUNEL), biochemical and stereological techniques. The rats in the UVAB, UVAB + CUR, and UVAB + ALA groups were subjected to UVAB irradiation for a period of two hours per day over the course of one month. The UVAB + CUR and UVAB + ALA groups were administered 100 mg/kg/day of curcumin and 100 mg/kg/day of α-lipoic acid via gavage 30 min prior to UVAB irradiation. The CUR group was administered 100 mg/kg/day of curcumin via gavage, while the ALA group received the same dose of α-lipoic acid. A significant change in the volume ratio of the dorsal skin epidermis and dermis was observed in the stereological findings of the rats in the UVAB group. These changes exhibited a favourable progression as a consequence of the CUR and ALA applications. In the UVAB group, TOS and OSI were significantly elevated as a consequence of the rise in oxidative stress. Conversely, the treatment groups demonstrated a notable reduction in TOS and OSI levels. The study also revealed a substantial increase in the number of apoptotic cells within the UVAB group. However, the treatment groups exhibited a significant decline in apoptotic cells. In conclusion, the findings suggest that CUR and ALA possess a protective effect against UVAB-induced skin damage., Competing Interests: Compliance with Ethical Standards Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Previous reports have characterized photosensitivity in atopic dermatitis (AD), but with differences in terminology and criteria., Objective: This study aims to assess outcomes in 139 patients with AD referred for photodiagnostic testing and to establish diagnostic criteria for photosensitivity in AD., Methods: Clinical and photodiagnostic data were reviewed, categorizing photosensitivity into photoexacerbated AD, photosensitive AD, and chronic actinic dermatitis., Results: Of the patient cohort, the mean age was 42.6 ± 16.7 years, and 61.9% were men. In total, 51.1% of the patients with photoexacerbated AD had normal monochromator phototesting, and 7.9% of the patients with photosensitive AD displayed slight-to-moderate ultraviolet (UV)-A sensitivity (≥30% of normal minimal erythema dose [MED]) and mostly normal or slightly reduced UV-B MEDs (≥80% of normal MED). Conversely, 41% of the patients had chronic actinic dermatitis, and 93% of this group demonstrated significant UV-B sensitivity, with very low UV-B MEDs (<80% of normal MED) and/or very low UV-A MEDs (<30% of normal MED). No significant differences in sex, age, or skin phototype were observed between the groups. Serial phototesting revealed changes in photosensitivity status over time in 8 patients., Limitations: A small sample size and retrospective design., Conclusions: This study highlights the heterogeneity of photosensitivity patterns in patients with AD and the importance of follow-up assessments due to potential shifts in disease spectrum over time., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Skin aging is one of the most abundant aging-related disorders that can be accelerated by excessive exposure to ultraviolet irradiation. Topically applied fermented skincare ingredients have gained mounting attentions due to their high concentration of various skin nourishing nutrients and bioactive components and low skin irritation potency., Aims: In the present study, we aim to fully demonstrate the skin-related benefits of a novel extract of Thermus thermophilus and Bacillus subtilis mixed-culture ferment (TBFE)., Methods: TBFE was prepared through an innovative mixed-culture fermentation process. The contents of nutrients and bioactive ingredients were quantified by different methods accordingly. Both in vitro tests and randomized controlled human trial were utilized to further demonstrate multifaceted beneficial effects on human skin, as well as the potential mechanisms., Results: Our results showed that TBFE upregulated the expression of type IV collagen, elastin, aquaporin-3, and dermal-epidermal junction markers, while inhibited production of melanin, in different skin cell models. Moreover, TBFE inhibited the generation of reactive oxygen species and pro-inflammatory mediators induced by ultraviolet irradiation in normal human keratinocytes, while stimulated autophagy in senescent keratinocytes. Results from clinical studies confirmed those in vitro findings, demonstrating that TBFE at 5% and 20% concentration provides anti-aging properties in subjects with sensitive skin, in terms of improving wrinkles, moisturization, and skin lightening., Conclusions: In summary, we demonstrate that a novel mixed-culture ferment extract has promising anti-aging effects, which may be attributed to anti-oxidation, anti-inflammation, and promotion of autophagy in skin cells., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Despite the loss of melanocytes, individuals with vitiligo have a significantly lower risk of developing skin malignancies compared to ethnicity-matched controls. The study investigated the molecular mechanisms that protect skin cells (keratinocytes) from UV-B-induced DNA damage in individuals with vitiligo. The study found that upregulation of stem cell factor (SCF) signaling significantly reduced γ-H2AX positivity and cyclobutane pyrimidine dimer formation and improved mitochondrial health (elongated mitochondria, reduced reactive oxygen species [ROS] and lipid peroxidation) in keratinocytes upon UV-B exposure. Interestingly, SCF treatment also reduced lipid droplet accumulation and triacylglyceride levels by upregulating lipoprotein lipase (LPL). Further, siLPL increased DNA damage and lipid droplet (LD) accumulation, while NO-1886, an LPL agonist, reversed both, suggesting a direct link between lipid metabolism and DNA damage. Downregulation of NAD-dependent deacetylase sirtuin1 (SIRT1) with siRNA or with Ex-527, a pharmacological inhibitor of SIRT1, diminished the protective effects mediated by SCF and NO-1886, suggesting SIRT1 to be the final effector protein in the SCF-LPL-SIRT1 signaling axis. Analysis of clinical samples of vitiligo corroborated the upregulation of SCF and LPL in lesional epidermis. In conclusion, our study demonstrates a novel SCF-LPL-SIRT1 signaling axis that confers protection to vitiligo keratinocytes from the harmful effects of UV-B radiation., (© 2024 Federation of American Societies for Experimental Biology.)

Appropriate photoprotection plays a key role in the safety of using medicinal preparations whose active substances may induce photosensitivity reactions. This aspect applies not only to drugs applied topically to the skin, but also systemically. Drug-induced photosensitivity reactions to light depend on the active substance contained in the medicinal product and its dose, which translates into the concentration in the skin, the type of ultraviolet radiation, its intensity and exposure time. The chemical structure of phototoxic drugs contains unsaturated chemical bonds and aromatic groups, which are responsible for the absorption of radiation, the formation of degradation products and/or free radicals and hypersensitivity reactions. Therefore, in order to prevent hypersensitivity reactions, it is necessary to use appropriate sun protection and/or avoid exposure to solar radiation during pharmacotherapy with selected groups of drugs. The paper presents the latest research results on the impact of drug-induced photohypersensitivity on the increased likelihood of skin cancer. Drugs with the potential to induce photohypersensitivity reactions are discussed, including information on the relationship between their long-term use and the incidence of skin cancer. Based on the data contained in the Product Characteristics, exemplary indications regarding the appropriate photoprotection method to ensure the safe use of the medicinal product are presented. Med Pr Work Health Saf. 2024;75(5):475-484., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Background: Ultraviolet B(UVB) triggers a pro-survival response through mitophagy, but the role of FUNDC1-mediated mitophagy in photodamaged skin remains unexplored., Objectives: To clarify the function of mitophagy in UVB-induced photodamaged skin., Methods: To investigate the role of FUNDC1-mediated mitophagy in UVB-induced mitochondrial damage and cell apoptosis, FUNDC1 knockdown in C57BL/6 mice was performed using adeno-associated virus. Additionally, FUNDC1 overexpression and knockdown in HaCaT cells were conducted using lentivirus. A comprehensive analysis was conducted on a panel of human sun-exposed skin samples, alongside control samples, to assess the expression levels of FUNDC1., Results: In UVB-induced C57BL/6 mice, the dorsal skin showed photodamage including erythema, scaling, erosion, and scabs. The expression levels of PINK1, Parkin, and BNIP3 did not show significant changes, while FUNDC1 expression consistently declined along with LC3B. Cytochrome C, Bax, and cleaved-caspase3 were upregulated, while Bcl2 was downregulated. UVB-induced HaCaT cells showed mitochondrial damage, accompanied by FUNDC1 downregulation and BNIP3 upregulation, while PINK1 and Parkin showed no significant changes. FUNDC1 overexpression led to an increase in mtROS and a decrease in mitochondrial membrane potential and ATP levels, indicating complete mitochondrial clearance and exacerbated cell death. FUNDC1 knockdown protected against UVB-induced photodamage in mice and mitigated mitochondrial damage and apoptosis in HaCaT cells by activating compensatory PINK1/Parkin-dependent mitophagy, which was evidenced by upregulation of PINK1 and Bcl2 and downregulation of Bax. In human sun-exposed skin samples, there was a decrease in the number of FUNDC1 + cells compared with non-sun-exposed controls., Conclusions: FUNDC1-mediated mitophagy regulates skin photodamage and provides a novel mechanism for resisting photodamage, presenting a potential target for future therapeutic interventions., Competing Interests: Declaration of competing interest The authors declare they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Dasatinib (DAS) is an anticancer drug employed in the treatment of certain hematological malignancies. Although DAS has been mainly developed for oral administration, it has recently garnered attention for its possible topical application. The use of topical drugs can cause photosensitivity, which is not listed as an adverse reaction for DAS. Since DAS absorbs UVA, it could potentially induce photosensitivity reactions and lead to oxidative damage to cellular targets. This study aims to investigate whether DAS exhibits phototoxic reactions on primary cellular targets in both solution and artificial skin, mimicking topical drug administration. It also examines the potential generation of highly reactive intermediates like organic radicals and ROS, which could trigger photosensitivity reactions. Upon DAS irradiation in the UVA region, the first transient species detected was the diradicaloid triplet excited state ( 3 DAS∗) with an absorption maximum of around 490 nm, which was quenched by oxygen to produce singlet oxygen. Quenching experiments with linoleic acid and 3-methylindole indicated that radical-mediated (Type I) photosensitized damage to lipids and proteins is possible. However, the lack of triplet quenching with guanosine suggests that the Type II mechanism also plays a role in the photooxidation of biomolecules. Accordingly, the neutral red uptake phototoxicity test (photoirritation factor of 5) and the comet assay, revealed that this drug is photo(geno)toxic to cells. Moreover, investigations on lipid photoperoxidation, and protein and DNA photooxidation strongly support that different cellular compartments are potential targets for DAS-induced phototoxicity. Regarding its potential application in topical dermatological formulations, an O/W emulsion of DAS was prepared and tested in reconstructed human epidermis, and a significant phototoxicity was also demonstrated. Fortunately, this undesired side effect disappeared upon formulation of DAS along with a sunscreen. Thus, for topical treatments, the photosensitivity reactions induced by DAS can be prevented by using formulations including appropriate UVA filters., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Inmaculada Andreu reports financial support, article publishing charges, and equipment, drugs, or supplies were provided by Spanish Ministry of Science and Innovation. Ignacio Vaya reports financial support and equipment, drugs, or supplies were provided by Generalitat Valenciana. Consellería de innovación, universidades, ciencia y sociedad digital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Non-coding mutations in the TERT promoter (TERTp), typically at one of two bases -124 and -146 bp upstream of the start codon, are among the most prevalent driver mutations in human cancer. Several additional recurrent TERTp mutations have been reported but their functions and origins remain largely unexplained. Here, we show that atypical TERTp mutations arise secondary to canonical TERTp mutations in a two-step process. Canonical TERTp mutations create de novo binding sites for ETS family transcription factors that induce favourable conditions for DNA damage formation by UV light, thus creating a hotspot effect but only after a first mutational hit. In agreement, atypical TERTp mutations co-occur with canonical driver mutations in large cancer cohorts and arise subclonally specifically on the TERTp driver mutant chromosome homolog of melanoma cells treated with UV light in vitro. Our study gives an in-depth view of TERTp mutations in cancer and provides a mechanistic explanation for atypical TERTp mutations., Competing Interests: Competing interests A.S. is a co-inventor of the SiMSen-Seq technology that is patent protected (U.S. Serial No.:15/552,618). A.S. declares stock ownership in Tulebovaasta, Iscaff Pharma and SiMSen Diagnostics, and is a board member of Tulebovaasta. The other authors declare no competing interests., (© 2024. The Author(s).)

Overexposure to ultraviolet radiation mainly leads to skin disorders (erythema, burns, immunosuppression), skin aging, and skin cancer as the most serious side effect. It has been widely accepted that using sunscreen products is an important way to protect against the harmful effects of UV rays. Although commercial sunscreens have constantly changed and improved over time, there are emerging concerns about the safety of conventional, organic, UV filters due to adverse effects on humans (such as photoallergic dermatitis, contact sensitivity, endocrine-disrupting effects, etc.) as well as accumulation in the environment and aquatic organisms. This is why natural compounds are increasingly being investigated and used in cosmetic and pharmaceutical sunscreens. Some of these compounds are widely available, non-toxic, safer for use, and have considerable UV protective properties and less side effects. Plant-based compounds such as flavonoids can absorb UVA and UVB rays and possess antioxidant, anticarcinogenic, and anti-inflammatory effects that contribute to photoprotection. Apart from flavonoids, other natural products such as certain vegetable oils, carotenoids, stilbenes, and ferulic acid also have UV-absorbing properties. Some vitamins might also be beneficial for skin protection due to their antioxidant activity. Therefore, the aim of this research was to gain insight into the potential of natural compounds to replace or reduce the amount of conventional UV filters, based on recent research.

Hydrochlorothiazide (HCTZ) is a widely utilized diuretic for the treatment of hypertension. The photosensitivity of HCTZ has been recognized for six decades, with UVA being considered the primary culprit. However, the precise molecular mechanism of HCTZ sensitizing skin to UV radiation remains unknown. In this study, we demonstrate that HCTZ exacerbates UVB-induced photosensitivity in normal skin by disrupting the DNA damage response, a crucial network responsible for maintaining epidermal homeostasis. Here, we found that HCTZ aggravates UVB-induced mouse skin damage. Through transcriptomic and proteomic profiling, we have found that the cell cycle and p53 signaling pathway may contribute to the photosensitivity caused by HCTZ. In keratinocytes, HCTZ promotes the transition from G1 to S phase and inhibits the p53 signaling pathway after exposure to UV radiation. We have found that HCTZ enhances the accumulation of DNA damage induced by UVB and impairs nucleotide excision repair (NER), which is responsible for repairing UVB-induced DNA lesions, by inhibiting the expression of NER-related genes and shortening the duration of G1 phase. Furthermore, pharmacologically inducing G1 arrest eliminates HCTZ-induced accumulation of damaged DNA. These findings unveil an unknown mechanism through which HCTZ impairs NER and interferes with UVB-induced cell cycle arrest, ultimately leading to improper response towards DNA damage and increased skin sensitivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ultraviolet (UV) B-induced damage in human epidermal keratinocytes (HEKs) initiates photocarcinogenesis. However, how diabetes influences photocarcinogenesis is not well understood. To investigate the impact of high-glucose environments on responses to UVB, we cultured HEKs in normal-glucose (NG) or high-glucose (HG) conditions (G6 and G26), followed by UVB irradiation at 25 mJ/cm 2 (G6UVB and G26UVB). We performed next-generation sequencing and analyzed HEKs' expression profiles bioinformatically to identify candidate genes and cellular responses involved. We found UVB induced consistent responses in both NG- and HG-cultivated HEKs, but it also triggered certain distinct processes and pathways specifically in the HG groups. The 459 differentially expressed (DE) genes in the HG groups revealed their roles in chromatin remodeling, nucleosome assembly, and interferon signaling activation. Moreover, the 29 DE genes identified in G26UVB/G6UVB comparison, including the potent tumor suppressor gene TFPI2, were considered key genes contributing to HEKs' altered response to UVB in HG environments. UVB irradiation induced significantly higher TFPI2 expression in HG-cultivated HEKs than their NG-cultivated counterpart. Finally, HG-cultivation significantly increased oxidative stress, cyclobutane pyrimidine dimer formation, and apoptosis, while reducing HEKs' viability after UVB irradiation. These changes under HG conditions probably mediate cell fate toward death and tumor regression. Overall, our findings provide evidence and associated molecular basis on how HG conditions reduce keratinocytes' photocarcinogenic potential following UVB exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Blumea balsamifera (L.) DC. (BB), the source of Blumea balsamifera oil (BBO), is an aromatic medicinal plant, renowned for its pharmacological properties and its traditional use in Southeast Asian countries such as China, Thailand, Vietnam, Malaysia, and the Philippines for centuries. Traditionally, BB has been used as a raw herbal medicine for treating various skin conditions like eczema, dermatitis, athlete's foot, and wound healing for skin injuries., Aim of the Study: This research aimed to explore the inhibitory effects of BBO on skin aging using two models: in vitro analysis with human dermal fibroblasts (HDF) under UVB-induced stress, and in vivo studies on UVA-induced dorsal skin aging in mice. The study sought to uncover the mechanisms behind BBO's anti-aging effects, specifically, its impact on cellular and tissue responses to UV-induced skin aging., Materials and Methods: We applied doses of 10-20 μL/mL of BBO to HDF cells that had been exposed to UVB radiation to simulate skin aging. We measured cell viability, and levels of reactive oxygen species (ROS), SA-β-gal, pro-inflammatory cytokines, and matrix metalloproteinases (MMPs). In addition, we investigated the involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways in mediating the anti-aging effects of BBO. Histopathological and biochemical analyses were conducted in a mouse model to examine the effects of BBO on UV-induced photoaging., Results: UV exposure accelerated aging, and caused cellular damage and inflammatory responses through ROS-mediated pathways. In HDF cells, BBO treatment countered the UVB-induced senescence, and the recovery of cell viability was correlated to notable reductions in SA-β-gal, ROS, pro-inflammatory cytokines, and MMPs. Mechanistically, the anti-aging effect of BBO was associated with the downregulation of the JNK/NF-κB signaling pathways. In the in vivo mouse model, BBO exhibited protective capabilities against UV-induced photoaging, which were manifested by the enhanced antioxidant enzyme activities and tissue remodeling., Conclusions: BBO effectively protects fibroblasts from UV-induced photoaging through the JNK/NF-κB pathway. Recovery from photoaging involves an increase in dermal fibroblasts, alleviation of inflammation, accelerated synthesis of antioxidant enzymes, and slowed degradation of ECM proteins. Overall, BBO enhances the skin's defensive capabilities against oxidative stress, underscoring its potential as a therapeutic agent for oxidative stress-related skin aging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Oxidative stress induced by medium-wavelength ultraviolet radiation (UVB) is one of the most dangerous environmental stressors for the skin. Therefore, various medicinal remedies aim to prevent the harmful effects of UVB or support the recovery of the damaged cells. This study aimed to evaluate the impact of bioactive phytocannabinoid cannabigerol (CBG) together with 3-O-ethyl ascorbic acid (EAA), a stable, lipophilic derivative of the antioxidant vitamin C, on UVB-induced changes of proteome in cultured human keratinocytes 24 h after treatment. Surprisingly, proteomic analysis revealed very prominent CBG and EAA effects on kinases. These changes mainly influenced ERK1/2, IKK, MAP3K7, MAPK14, RIPK2, and NLK. Their expression was decreased by CBG and EAA, especially if used together after UVB-irradiation, so the effects of UVB were abolished restoring the profile of kinases to non-irradiated control. Moreover, CBG and EAA also reduced the UVB-induced modifications of proteins by the lipid peroxidation product 4-hydroxynonenal, especially in the case of AKT, Camkk1, cJun, ERK1, IKKα, MAPK11 and PERK. We conclude that, by maintaining proteome stability and kinase-dependent signalling, both CBG and EAA may support the recovery of human keratinocytes exposed to UVB radiation, especially if applied together, while the time-dependence of these effects should be further studied., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Ultraviolet (UV) radiation is the primary extrinsic factor in skin aging, contributing to skin photoaging, actinic keratosis (AK), and even squamous cell carcinoma (SCC). Currently, the beneficial role of mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) in cutaneous wound healing has been widely reported, but the field of photoaging remains to be explored. Our results suggested that human umbilical cord MSC-derived sEVs (hucMSC-sEVs) intervention could effectively alleviate skin photoaging phenotypes in vivo and in vitro, including ameliorating UV-induced histopathological changes in the skin and inhibiting oxidative stress and collagen degradation in dermal fibroblasts (DFs). Mechanistically, pretreatment with hucMSC-sEVs reversed UVA-induced down-regulation of pregnancy zone protein (PZP) in DFs, and achieved photoprotection by inhibiting matrix metalloproteinase-1 (MMP-1) expression and reducing DNA damage. Clinically, a significant decrease in PZP in AK and SCC in situ samples was observed, while a rebound appeared in the invasive SCC samples. Collectively, our findings reveal the effective role of hucMSC-sEVs in regulating PZP to combat photoaging and provide new pre-clinical evidence for the potential development of hucMSC-sEVs as an effective skin photoprotective agent., (© The Author(s) 2024. Published by Oxford University Press.)

DNA double-strand breaks (DSBs) represent one of the most severe forms of genetic damage in organisms, yet vertebrate models capable of monitoring DSBs in real-time remain scarce. BRCA1/BRCA2-containing complex subunit 3 (BRCC3), also known as BRCC36, functions within various multiprotein complexes to mediate diverse biological processes. However, the physiological role of BRCC3 in vertebrates, as well as the underlying mechanisms that govern its activity, are not well understood. To explore these questions, we generated brcc3 -knockout zebrafish using CRISPR/Cas9 gene-editing technology. While brcc3 mutant zebrafish appear phenotypically normal and remain fertile, they exhibit significantly increased rates of mortality and deformity following exposure to DNA damage. Furthermore, embryos lacking Brcc3 display heightened p53 signaling, elevated γ-H2AX levels, and increased apoptosis in response to DNA-damaging agents such as ultraviolet (UV) light and Etoposide (ETO). Notably, genetic inactivation of p53 or pharmacological inhibition of Ataxia-telangiectasia mutated (ATM) activity rescues the hypersensitivity to UV and ETO observed in Brcc3-deficient embryos. These findings suggest that Brcc3 plays a critical role in DNA damage response (DDR), promoting cell survival during embryogenesis. Additionally, brcc3 -null mutant zebrafish offer a promising vertebrate model for real-time monitoring of DSBs.

Lipid extracts from the microalgae Nannochloropsis oceanica and Chlorococcum amblystomatis have great potential to prevent ultraviolet A (UVA)-induced metabolic disorders. Therefore, the aim of this study has been to analyze their cytoprotective effect, focused on maintaining intracellular redox balance and inflammation in UVA-irradiated skin fibroblasts, at the proteome level. The above lipid extracts reversed the suppression of the antioxidant response caused by UVA radiation, which was more visible in the case of C. amblystomatis . Modulations of interactions between heme oxygenase-1 and matrix metalloproteinase 1/Parkinson's disease protein 7/transcript1-α/β, as well as thioredoxin and migration inhibitory factor/Parkinson's disease protein 7/calnexin/ATPase p97, created key molecular signaling underlying their cytoprotective actions. Moreover, they reduced pro-inflammatory processes in the control group but they also showed the potential to regulate the cellular inflammatory response by changing inflammasome signaling associated with the changes in the caspase-1 interaction area, including heat shock proteins HSP90, HSPA8, and vimentin. Therefore, lipid extracts from N. oceanica and C. amblystomatis protect skin fibroblast metabolism from UVA-induced damage by restoring the redox balance and regulating inflammatory signaling pathways. Thus, those extracts have proven to have great potential to be used in cosmetic or cosmeceutical products to protect the skin against the effects of solar radiation. However, the possibility of their use requires the evaluation of their effects at the skin level in in vivo and clinical studies.

The skin is the largest organ in the human body and is made up of various cells and structures. Over time, the skin will age, which is not only influenced by internal factors, but also by external environmental factors, especially ultraviolet radiation. Aging causes immune system weakening in the elderly, which makes them more susceptible to dermatosis, such as type 2 inflammatory mediated pruritus. The immune response in this condition is marked by senescent cells consistently releasing low amounts of pro-inflammatory cytokines through a senescence-associated secretory phenotype (SASP). This continuous inflammation may accelerate immune system aging and establish a connection between immune aging and type 2 inflammatory skin diseases. In addition, two chronic pigmentation disorders, vitiligo and chloasma, are also associated with skin aging. Aged cells escape the immune system and accumulate in tissues, forming a microenvironment that promotes cancer. At the same time, "photoaging" caused by excessive exposure to ultraviolet radiation is also an important cause of skin cancer. This manuscript describes the possible links between skin aging and type 2 inflammation, chronic pigmentation disorders, and skin cancer and suggests some treatment options., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Lin, Han, Huang, Zhou, Wang, Zhou, Han and Chen.)

Regular and adequate use of broad-spectrum sunscreen has been proven to offer significant protection against acute Ultraviolet-induced photodamage, photoaging, immunosuppression, and the development of skin tumors. However, concerns regarding the safety and standardized use of sunscreens persist, including potential allergenicity and irritability of certain organic sunscreens, the impact of systemic absorption on the endocrine system, the effect on vitamin D synthesis and absorption, and environmental implications. Special caution is advised when using small molecule organic sunscreens and nanoparticle inorganic sunscreens, especially for infants, pregnant women, and areas with damaged skin.

Skin photoaging, primarily caused by ultraviolet (UV) radiation, leads to skin metabolic disorders, which have adverse psychological and physiological effects on individuals. However, traditional medications for repairing skin photoaging cause side effects. Natural bioactive compounds have been shown to prevent and treat skin photoaging with fewer side effects. Epigallocatechin gallate (EGCG), the main substance in tea polyphenols, is a natural bioactive compound with a range of properties. This review summarizes the beneficial effects and mechanisms of EGCG, as well as the application forms of EGCG in repairing photoaged skin. Results indicated that EGCG has repair effects, including improving elasticity, enhancing moisturization, inhibiting damage, and reducing pigmentation of photoaged skin. It has also been demonstrated that EGCG delivery systems, modified EGCG, and combinations with other bioactive substances could be used for repairing photoaged skin due to its poor stability and low bioavailability. EGCG effectively repairs various types of skin damage caused by UV radiation while maintaining normal skin structure and function. It is, therefore, an effective candidate for repairing photoaged skin. These results could provide references for the development and application of EGCG products for the treatment of photoaged skin.

Acne is a multifactorial inflammatory disease with a robust microbial component and numerous correlations with dysbiosis states. Furthermore, various factors are recognized as triggers for skin dysbiosis, including the use of certain cosmetics. Based on these arguments, we hypothesized that using photoprotective formulations could trigger dysbiosis and the occurrence of acne manifestations. To verify this assumption, six volunteers between 19 and 23 years of age, meeting all the inclusion criteria, received two applications a day of a non-commercial sunscreen formulation developed with the sun filters ethylhexyl methoxycinnamate, ethylhexyl salicylate, methyl anthranilate, and octocrylene dispersed in a base gel, with an estimated protection factor of 28.8. The pure base gel was used as a control. The samples were applied to an area delimited by a standard template (15 cm 2 ) in an amount corresponding to 30 mg (2 mg cm 2 ) for ten days. At two points in time, pre- and post-sample applications, the facial skin surface was swabbed to collect extracted DNA and processed to verify divergent degrees of 16 S RNA coding sequences. The data obtained allowed us to determine the abundance of different bacterial entities at the genus and species levels. The results showed that critical species of the acne process, such as Cutibacterium acnes and Staphylococcus epidermidis, seem to tolerate the evaluated formulation well and are not significantly affected by the formulation, suggesting no interference of its use concerning dysbiosis induction. These findings refute the idea that photoprotectors may cause skin dysbiosis in men., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Public health and clinical medicine should identify and characterize modifiable risk factors for skin cancer in order to facilitate primary prevention. In existing literature, the impact of occupational exposure on skin cancer, including malignant melanoma and non-melanoma skin cancers, has been extensively studied. This review summarizes the available epidemiological evidence on the significance of occupational risk factors and occupations associated with a higher risk in skin cancer. The results of this review suggest that there is sufficient epidemiological evidence to support the relationship between the increased risk of non-melanoma skin cancers and occupational exposure to solar radiation, ultraviolet radiation, ionizing radiation, arsenic and its compounds, and mineral oils. Occupational exposure to pesticides and polychlorinated biphenyls appears to provide sufficient epidemiological evidence for melanoma, and a higher risk of melanoma has been reported among workers in petroleum refining and firefighters. This comprehensive analysis will establish a foundation for subsequent investigations and developing targeted interventions of focused preventive measures against skin cancer among the working population., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Black tea is believed to strengthen the ability of the body to defend itself against external stimuli. Here, by examining Caenorhabditis elegans (C. elegans) locomotor behavior over a short period after UV stress, we found that feeding black tea extract (BTE) caused worms to enter a superior stress-induced sleep (SIS) state, which potentially boosting organismal recovery. BTE enhances SIS through KIN-29 mediated epidermal growth factor signaling and modulation of sleep by specific interneurons ALA and RIS. It also inhibits lipid degradation during sleep. These functions were also observed when theaflavins (TFs) were fed. In conclusion, our results describe a new way for BTE-enhanced damage repair in C. elegans after UV stress that relies on enhanced SIS, and confirm the contribution of TFs therein., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Exposure to solar ultraviolet-B (UV-B) radiation significantly accelerates skin aging by inducing the expression of matrix metalloproteinases (MMPs) such as MMP-1, leading to alterations in the extracellular matrix and consequent photoaging. Some plant components, renowned for their UV-absorbing and antioxidative properties, show potential for mitigating photoaging by reducing UV-B-induced MMP levels. In this context, we explored the inhibitory effects of Clerodendrum trichotomum extract (CTE) on UV-B-induced skin damage., Methods: The mechanism of CTE was predicted using network pharmacology approach. Also, antiaging efficacy was evaluated by mouse model and cellular system using human epidermal keratinocytes (HEKa), including its modulation of mitogen-activated protein kinase (MAPK) signaling pathways., Results: CTE effectively counters UV-B-induced skin damage, as evidenced by the suppression of MMP-9 and MMP-1 expression in mice. We found that each fraction and chemical constituents of CTE suppressed UV-B-induced MMP-1 secretion in HEKa cells., Conclusion: CTE inhibits UV-B-induced skin aging by partially suppressing MMP-1 and MMP-9 secretion via the modulation of MAPK signaling pathways., (© 2024 The Author(s). Photodermatology, Photoimmunology & Photomedicine published by John Wiley & Sons Ltd.)

Osteopontin (OPN) is a pro-inflammatory protein that influences bone remodelling, wound healing, angiogenesis, allergic inflammation, and skin diseases such as psoriasis, contact dermatitis and skin cancer. However, the role of OPN in the skin remains unclear. Therefore, this study aimed to investigate the role of OPN in the skin, particularly in the context of ultraviolet (UV) irradiation-induced inflammation. OPN expression and its effects on inflammatory modulators were assessed in human skin, in a mouse model and in vitro , using a UV source emitting both UVB and UVA radiation, which collectively contribute to UV-induced skin inflammation. OPN expression increased in human and mouse skin after UV irradiation. Compared with wild-type mice, UV irradiation-induced skin phenotypes, such as erythema and skin thickening, were alleviated in OPN -/- mice. In addition, the number of immune cells recruited to the skin after UV irradiation and the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) were observed to be decreased in the skin of OPN -/- mice compared with that of wild-type mice. By contrast, the degree of skin inflammation was higher in the hOPN KI mice than in wild-type mice. Treatment with recombinant OPN increased the expression of MMP-1 and inflammatory cytokines in human dermal fibroblasts and epidermal keratinocytes in vitro . Our results suggest that OPN may play a regulatory role in UV-induced skin inflammation.

Background: Mitochondria could be an important target for ultraviolet radiation (UVR)-induced skin damage. Therefore, protecting mitochondria using mitochondria-targeted antioxidants may protect skin from UV-induced photodamage., Methods: In the present study, UVR-induced skin damage model was developed by irradiating male Wistar rats with UVB at a dose of 120 mJ/cm 2 , twice a week for a period of 5 weeks. Mito-TEMPO was administered intraperitoneally (0.1 mg/kg b.w.) twice a week for 5 weeks. After 5 weeks of treatment period, animals were sacrificed and the dorsal skin tissues were collected. Physical examinations of the skin for analyzing wrinkle formation and epidermal thickening were carried out. Skin tissues were used for the evaluation of histopathological changes, mitochondrial dysfunction analysis, and mitochondrial membrane potential., Results: Physical and histological examination showed that mito-TEMPO protected from the damaging effect of UVB radiation. A significant increase in mitochondrial reactive oxygen species (mtROS) generation with a concomitant increase in mitochondrial lipid peroxidation (mtLPO) was observed in UV-irradiated groups. UV-induced generation of mtROS and mtLPO formation was effectively reduced by mito-TEMPO. Mito-TEMPO pre-treatment improved mitochondrial complex II activity, which was significantly reduced in the UV-irradiated group., Conclusion: The results suggested that mito-TEMPO effectively protected skin tissue against UV-induced oxidative stress and damage., (© 2024 The Author(s). Photodermatology, Photoimmunology & Photomedicine published by John Wiley & Sons Ltd.)

The greatest risk factor for skin cancer is exposure to ultraviolet (UV) rays of the sun. Among the three types of solar radiation (UVA, UVB, UVC), UVB rays are most commonly associated with skin cancer. UVB exposure promotes the formation of cyclobutane pyrimidine dimers (CPDs) in the DNA of cells in the epidermal skin layers, which can lead to mutations as DNA repair machinery attempts to repair the damage. These mutations can lead directly to skin carcinogenesis. Previous studies in animal and in human ex vivo skin models have shown that topical application of acyclothymidine dinucleosides protects DNA from UV-induced damage by preventing the formation of CPDs and helps initiate repair through the activation of DNA repair enzymes. Here we review the biological evidence leading to the development and formulation of ProteXidineTM (Topix Pharmaceuticals, Inc., Amityville, NY), as a UV protective agent for topical human application. We also provide clinical data pertaining to four ProteXidineTM formulations (test materials 1-4) tested for their abilities to reduce CPDs in an ex vivo human skin tissue model. J Drugs Dermatol. 2024;23(11):953-956. doi:10.36849/JDD.8420.

Skin cancer most commonly affects fair-skinned individuals1; however, it can appear in individuals of all skin tones. Photoprotective behaviors such as applying sunscreen should be practiced by all individuals regardless of skin tone. Herein, the authors discuss the cost and protection of popular sunscreens targeted towards patients with darker skin or skin of color (SOC), and suggest important considerations providers should take into account when advising about sunscreen recommendations for patients with skin of color. J Drugs Dermatol. 2024;23(11):e181-e182. doi:10.36849/JDD.8710e.

Ultraviolet (UV) radiation-triggered production of reactive oxygen species (ROS) is a primary contributor to apoptosis in human lens epithelial cells (HLECs), which can ultimately result in cataract formation. The nuclear factor erythroid-2-related factor 2 (Nrf2)-Kelch ECH associating protein 1 (Keap1) pathway, a fundamental oxidative stress regulation mechanism, plays a crucial role in the development of cataracts. Ferulic acid (FA), recognized for its potent antioxidant properties can activate the Nrf2 signaling pathway to mitigate oxidative damage and cell apoptosis. In this study, we have demonstrated the protective effects of FA in reducing UVA-induced oxidative damage and apoptosis in HLECs through the modulation of the Keap1/Nrf2 pathway, as evidenced by both cellular and animal experiments. HLECs and Lens were exposed to 10 J/cm 2 UVA radiation with or without prior treatment with FA. We found that UVA radiation increased oxidative damage and cell apoptosis in HLECs, ultimately leading to opacification of rat lenses, while FA was able to attenuate both oxidative damage and cell apoptosis in HLECs and reduce the degree of lens opacification. FA upregulated the expression of antioxidant response factors of the Keap1/Nrf2 pathway and downregulated the expression of apoptosis-related genes in HLECs, as demonstrated by Western blot and RT-qPCR analyses. We also found that UVA radiation increased the degree of demethylation of the Keap1 promoter in HLECs, whereas FA reduced the level of Keap1 promoter demethylation as determined by DNA sequencing. Additionally, UVA upregulated the expression of DNA active demethylase of the Keap1 promoter in HLECs, Dnmt1, Dnmt3a, and Dnmt3b, as shown by immunofluorescence, Western blot, and RT-qPCR, however, FA attenuated the activity of the passive demethylase TET1 in addition to the active demethylases. These results demonstrated that UVA radiation can cause oxidative damage, cell apoptosis, and rat lens opacification by increasing the demethylation of the Keap1 promoter in lens epithelial cells. Conversely, FA was shown to reduce oxidative damage, inhibit cell apoptosis, and decrease rat lens opacification by increasing the methylation of the Keap1 promoter. These findings suggest that FA could be therapeutically beneficial in preventing and mitigating cataracts induced by UVA radiation., (© 2024 Wiley Periodicals LLC.)