UV-induced Cell Research Articles

Ultraviolet Light Causes Skin Cell Senescence: From Mechanism to Prevention Principle.

The skin is an effective protective barrier that significantly protects the body from damage caused by external environmental factors. Furthermore, skin condition significantly affects external beauty. In today's era, which is of material and spiritual prosperity, there is growing attention on skincare and wellness. Ultraviolet radiation is one of the most common external factors that lead to conditions like sunburn, skin cancer, and skin aging. In this review, several mechanisms of UV-induced skin cell senescence are discussed, including DNA damage, oxidative stress, inflammatory response, and mitochondrial dysfunction, which have their own characteristics and mutual effects. As an illustration, mitochondrial dysfunction triggers electron evasion and the generation of more reactive oxygen species, leading to oxidative stress and the activation of the NLRP3 inflammasome, which in turn causes mitochondrial DNA (mt DNA) damage. Based on the current mechanism, suitable prevention and treatment strategies are proposed from sunscreen, dietary, and experimental medications respectively, aimed at slowing down skin cell aging and providing protection from ultraviolet radiation. The effects of ultraviolet rays on skin is summarized, offering insights and directions for future studies on mechanism of skin cell senescence, with an anticipation of discovering more effective prevention and cure methods.

Ultra-small platinum nano-enzymatic spray with ROS scavenging and anti-inflammatory properties for photoaging treatment

Photoaging induced by ultraviolet (UV) results in oxidative stress and inflammation. Noble metal nanozymes have strong antioxidant and anti-inflammatory capacity, which are expected to eliminate the excessive reactive oxygen species (ROS) and inflammatory factors in the photoaged skin. Hence, we have synthesized ultrasmall platinum nanoparticles coated with polyvinylpyrrolidone (Pt NPs) with a diameter of nearly 5 nm for photoaging treatment. Thanks to multi-enzymatic capacities (catalase, peroxidase, and superoxide dismutase) of Pt NPs, they can effectively protect fibroblasts from UV-induced ROS attack, relieve fibroblasts from UV-induced cell cycle arrest, downregulate matrix metalloproteinases (MMPs) to regenerate type I collagen, and inhibit M1 macrophage polarization to decrease the expression of inflammatory factors. For photoaged mice treatment, we employ the concept of routine spray skincare and encapsulate Pt NPs solution in a spray bottle. In combination with roller needle, following Pt NPs nano-enzymatic spray given, UV-induced photoaged mice display reduced wrinkle formation in the collagen-depleted dermal tissue of mice and more youthful performance in both appearance and organizational structure. Consequently, multi-enzymatic functions of Pt NPs nano-spray offers a promising avenue for anti-photoaging therapy, providing potential benefits in both preventative and restorative skincare applications.

CryoEM reveals the structure of an archaeal pilus involved in twitching motility

Amongst the major types of archaeal filaments, several have been shown to closely resemble bacterial homologues of the Type IV pili (T4P). Within Sulfolobales, member species encode for three types of T4P, namely the archaellum, the UV-inducible pilus system (Ups) and the archaeal adhesive pilus (Aap). Whereas the archaellum functions primarily in swimming motility, and the Ups in UV-induced cell aggregation and DNA-exchange, the Aap plays an important role in adhesion and twitching motility. Here, we present a cryoEM structure of the Aap of the archaeal model organism Sulfolobus acidocaldarius. We identify the component subunit as AapB and find that while its structure follows the canonical T4P blueprint, it adopts three distinct conformations within the pilus. The tri-conformer Aap structure that we describe challenges our current understanding of pilus structure and sheds new light on the principles of twitching motility.

Blocking the ATR-SerRS-VEGFA pathway targets angiogenesis for UV-induced cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer, with an escalating incidence rate and a notable potential (up to 5%) for metastasis. Ultraviolet radiation (UVA and UVB) exposure is the primary risk factor for cSCC carcinogenesis, with literature suggesting ultraviolet radiation (UVR) promotes vascular endothelial growth factor A (VEGFA)expression. This study aims to investigate UVR-induced upregulation of VEGFA and explore combination therapeutic strategies. The skin squamous cell carcinoma cell line A431 was exposed to specific durations of ultraviolet radiation. The effect of emodin on ATR/SerRS/VEGFA pathway was observed. The cell masses were also transplanted subcutaneously into mice (n = 8). ATR inhibitor combined with emodin was used to observe the growth and angiogenesis of the xenografts. The results showed that UV treatment significantly enhanced the phosphorylation of SerRS and the expression level of VEGFA in A431 cells (p < 0.05). Treatment with emodin significantly inhibited this expression (p < 0.05), and the combination of emodin and ATR inhibitor further enhanced the inhibitory effect (p < 0.05). This phenomenon was further confirmed in the xenograft model, which showed that the combination of ATR inhibitor and emodin significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.05), thus showing an inhibitory effect on cSCC. This study innovatively reveals the molecular mechanism of UV-induced angiogenesis in cSCC and confirms SerRS as a novel target to inhibit cSCC angiogenesis and progression in vitro and in vivo studies.

Anti-Aging Properties of Cannabis sativa Leaf Extract against UVA Irradiation

Hemp extract has garnered interest as a potential cosmeceutical agent with multifunctional activities, particularly in protecting against UV-induced skin cell aberrations and restoring aged skin cells. The ethanolic extract of Cannabis sativa leaves was prepared into an aqueous solution (CLES) to investigate its anti-photoaging ability. HPLC analysis revealed that the CLES contained 1.64 ± 0.01% w/w of cannabidiol and 0.11% w/w of ∆9-tetrahydrocannabinol. Additionally, the total phenolic content was found to be 4.08 ± 0.30 mg gallic acid equivalent per g of solution using the Folin–Ciocalteu method. The CLES exhibited potent scavenging activity using a DPPH assay, with an EC50 value of 277.9 ± 2.41 μg/mL, comparable to L-ascorbic acid, with 2.19 ± 0.28 μg/mL. The anti-photoaging potential of the CLES was evaluated using UVA-irradiated and in vitro-aged fibroblasts as a model. Pre-treatment with 20 μg/mL CLES for 24 h significantly alleviated the reduction in type I procollagen and suppressed the overproduction of MMP-1 and IL-6 induced by UVA. Moreover, the percentage of senescence-associated β-galactosidase-expressing cells decreased significantly to 11.9 ± 0.5% in the aged cells treated with CLES compared with untreated cells (18.8 ± 3.8%). These results strongly indicate the cosmeceutical potential of the CLES as an effective active agent for the anti-photoaging prevention and/or treatment.

CircRNA HLCS regulates lens epithelial cell apoptosis via miR-338-3p/BPNT1 axis.

The purpose of this study was to investigate the effect of circ_HLCS on age-related cataract (ARC). Circ_HLCS, microRNA (miR)-338-3p, and bisphosphate 3'-nucleotidase 1 (BPNT1) were quantified by quantitative real-time polymerase chain reaction or western blot. Cell proliferation and cell viability were assessed by the 5-Ethynyl-2'-deoxyuridinr and cell counting kit-8 assays. Cell apoptosis was detected by flow cytometry. Targeted correlations among circ_HLCS, miR-338-3p, and BPNT1 were verified by the dual-luciferase reporter and RNA pull-down assays. circ_HLCS was diminished in ARC tissues and UV-treated SRA01/04 cells. Elevated content of circ_HLCS undermined UV-induced cell proliferation inhibition and apoptosis. Mechanistically, circ_HLCS directly targeted miR-338-3p, and circ_HLCS regulated BPNT1 expression through miR-338-3p. Furthermore, reduction of miR-338-3p ameliorated UV-induced SRA01/04 cell damage by increasing BPNT1 expression. Taken together, these data suggested that circ_HLCS inhibited apoptosis of UV-treated SRA01/04 cells by miR-338-3p/BPNT1 axis. Therefore, circ_HLCS might be a potential therapeutic target for ARC.

FTO-mediated regulation of m6A methylation is closely related to apoptosis induced by repeated UV irradiation

BackgroundUltraviolet (UV) damage is closely related to skin photoaging and many skin diseases, including dermatic tumors. N6-methyladenosine (m6A) modification is an important epigenetic regulatory mechanism. However, the role of m6A methylation in apoptosis induced by repeated UV irradiation has not been characterized. ObjectiveTo explore m6A methylation changes and regulatory mechanisms in the repeated UV-induced skin damage process, especially apoptosis. MethodsHaCaT cells and BALB/c-Nu nude mice were exposed to repeated UVB/UVA+UVB irradiation. Colorimetry and flow cytometry were used to measure cellular viability and apoptosis. m6A-modified genes were detected via colorimetry and methylated RNA immunoprecipitation (MeRIP) sequencing. Methyltransferases and demethylases were detected via RT-PCR, western blotting and immunohistochemistry. Transfection of siRNA and plasmid was performed to knock down or overexpress the selected genes. ResultsAfter UVB irradiation, 861 m6A peaks were increased and 425 m6A peaks were decreased in HaCaT cells. The differentially modified genes were enriched in apoptosis-related pathways. The m6A demethylase FTO was decreased in both HaCaT cells and mouse skin after UV damage. Overexpressing FTO could improve cell viability, inhibit apoptosis and decrease RNA-m6A methylation, including LPCAT3-m6A, which increase LPCAT3 expression, cell viability promotion and apoptosis inhibition. ConclusionOur study identified the cell m6A methylation change lists after repeated UVB irradiation, and revealed that FTO and LPCAT3 play key roles in the m6A methylation pathogenesis of UV-induced skin cell apoptosis. FTO-m6A-LPCAT3 might serve as a novel upstream target for preventing and treating photoaging and UV-induced skin diseases.

Sesamin attenuates UVA-induced keratinocyte injury via inhibiting ASK-1-JNK/p38 MAPK pathways.

Ultraviolet (UV) exposure-stimulated reactive oxygen species (ROS) formation in keratinocytes is a crucial factor in skin aging. Phytochemicals have become widely popular for protecting the skin from UV-induced cell injury. Sesamin (SSM) has been shown to play a role in extensive pharmacological activity and exhibit photoprotective effects. To assess the protective effect of SSM on UVA-irradiated keratinocytes and determine its potential antiphotoaging effect. HaCaT keratinocytes pretreated with SSM were exposed to UVA radiation at 8 J/cm2 for 10 min. Cell viability and oxidative stress indicators were evaluated using a cell counting kit-8 and lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) assay kits. Apoptosis and intracellular ROS levels were analyzed using annexin V-fluorescein isothiocyanate/propyridine iodide and dichlorodihydrofluorescein diacetate staining, respectively. Protein levels of matrix metalloprotein-1 (MMP-1), MMP-9, Bax/Bcl-2, and mitogen-activated protein kinase (MAPK) pathway proteins, phospho-apoptosis signal-regulating kinase-1 (p-ASK-1)/ASK-1, phospho-c-Jun N-terminal protein kinase (p-JNK)/JNK, and p-p38/p38 were determined using western blotting. Sesamin showed no cytotoxicity until 160 μmol/L on human keratinocytes. Sesamin pretreatment (20 and 40 μM) reversed the suppressed cell viability, increased LDH release and MDA content, decreased cellular antioxidants GSH and SOD, and elevated intracellular ROS levels, which were induced by UVA irradiation. Additionally, SSM inhibited the expression of Bax, MMP-1, and MMP-9 and stimulated Bcl-2 expression. In terms of the regulatory mechanisms, we demonstrated that SSM inhibits the phosphorylation of ASK-1, JNK, and p38. The results suggest that SSM attenuates UVA-induced keratinocyte injury by inhibiting the ASK-1-JNK/p38 MAPK pathways.

Tremella fuciformis polysaccharides alleviates UV-provoked skin cell damage via regulation of thioredoxin interacting protein and thioredoxin reductase 2.

Skin is exposed to a wide range of environmental risk factors including ultraviolet (UV) and all kinds of pollutants. Excessive UV exposure contributes to many disorders, such as photoaging, skin inflammation, and carcinogenesis. Previous studies have shown that Tremella fuciformis polysaccharides (TFPS) have protective effects on oxidative stress in cells, but the specific protective mechanism has not been clarified. To determine the effects of TFPS on UV-irritated human skin, we conducted a variety of studies, including Cell Counting Kit-8 (CCK-8), trypan blue, Western blot, apoptosis assays, reactive oxygen species (ROS) detection in primary skin keratinocytes, and chronic UV-irradiated mouse model. We first determined that TFPS protects human skin keratinocytes against UV radiation-induced apoptosis and ROS production. Moreover, TFPS regulates thioredoxin interacting protein (TXNIP) and thioredoxin reductase 2 (TXNRD2) levels in primary skin keratinocytes for photoprotection. Last, we found that topical TFPS treatment could alleviate the UV-induced skin damage in chronic UV-irradiated mouse model. Collectively, our work indicates the beneficial role of TFPS in UV-induced skin cell damage and provides a novel therapeutic reagent to prevent or alleviate the progress of photoaging and other UV-provoked skin diseases.

Hyperoside as a UV Photoprotective or Photostimulating Compound-Evaluation of the Effect of UV Radiation with Selected UV-Absorbing Organic Compounds on Skin Cells.

Ultraviolet (UV) radiation is a non-ionizing radiation, which has a cytotoxic potential, and it is therefore necessary to protect against it. Human skin is exposed to the longer-wavelength components of UV radiation (UVA and UVB) from the sun. In the present paper, we focused on the study of eight organic UV-absorbing compounds: astragalin, beta-carotene, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, hyperoside, 3-(4-methylbenzylidene)camphor, pachypodol, and trans-urocanic acid, as possible protectives of skin cells against UVA and UVB radiation. Their protective effects on skin cell viability, ROS production, mitochondrial membrane potential, liposomal permeability, and DNA integrity were investigated. Only some of the compounds studied, such as trans-urocanic acid and hyperoside, had a significant effect on the examined hallmarks of UV-induced cell damage. This was also confirmed by an atomic force microscopy study of morphological changes in HaCaT cells or a study conducted on a 3D skin model. In conclusion, hyperoside was found to be a very effective UV-protective compound, especially against UVA radiation. Commonly used sunscreen compounds such as 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, and 3-(4-methylbenzylidene)camphor turned out to be only physical UV filters, and pachypodol with a relatively high absorption in the UVA region was shown to be more phototoxic than photoprotective.

Ultraviolet radiation shapes dendritic cell leukaemia transformation in the skin

Tumours most often arise from progression of precursor clones within a single anatomical niche. In the bone marrow, clonal progenitors can undergo malignant transformation to acute leukaemia, or differentiate into immune cells that contribute to disease pathology in peripheral tissues1–4. Outside the marrow, these clones are potentially exposed to a variety of tissue-specific mutational processes, although the consequences of this are unclear. Here we investigate the development of blastic plasmacytoid dendritic cell neoplasm (BPDCN)—an unusual form of acute leukaemia that often presents with malignant cells isolated to the skin5. Using tumour phylogenomics and single-cell transcriptomics with genotyping, we find that BPDCN arises from clonal (premalignant) haematopoietic precursors in the bone marrow. We observe that BPDCN skin tumours first develop at sun-exposed anatomical sites and are distinguished by clonally expanded mutations induced by ultraviolet (UV) radiation. A reconstruction of tumour phylogenies reveals that UV damage can precede the acquisition of alterations associated with malignant transformation, implicating sun exposure of plasmacytoid dendritic cells or committed precursors during BPDCN pathogenesis. Functionally, we find that loss-of-function mutations in Tet2, the most common premalignant alteration in BPDCN, confer resistance to UV-induced cell death in plasmacytoid, but not conventional, dendritic cells, suggesting a context-dependent tumour-suppressive role for TET2. These findings demonstrate how tissue-specific environmental exposures at distant anatomical sites can shape the evolution of premalignant clones to disseminated cancer.

Epidermal mutation accumulation in photodamaged skin is associated with skin cancer burden and can be targeted through ablative therapy

The main carcinogen for keratinocyte skin cancers (KCs) such as basal and squamous cell carcinomas is ultraviolet (UV) radiation. There is growing evidence that accumulation of mutations and clonal expansion play a key role in KC development. The relationship between UV exposure, epidermal mutation load, and KCs remains unclear. Here, we examined the mutation load in both murine (n = 23) and human (n = 37) epidermal samples. Epidermal mutations accumulated in a UV dose-dependent manner, and this mutation load correlated with the KC burden. Epidermal ablation (either mechanical or laser induced), followed by spontaneous healing from underlying epithelial adnexae reduced the mutation load markedly in both mouse (n = 8) and human (n = 6) clinical trials. In a model of UV-induced basal cell carcinoma, epidermal ablation reduced incident lesions by >80% (n = 5). Overall, our findings suggest that mutation burden is strongly associated with KC burden and represents a target to prevent subsequent KCs.

Skewing of UV-induced cell death pathways using TLR4 ligands

Abstract Toll-like receptor 4 (TLR4) is a canonical innate immune receptor for the Gram-negative bacterial outer membrane component lipopolysaccharide (LPS). TLR4 deficiency has been shown to contribute to UV-induced carcinogenesis in epidermal cells. UV-induced cellular damage results in apoptosis which is characterized by a non-inflammatory cell death through the cleavage and activation of caspase-3. Utilizing bacterial enzyme combinational chemistry (BECC) we generated hypoacylated lipid A moieties from Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium which have moderately attenuated immune-stimulatory capacity. Continuously exposing TLR4 to these innate immune ligands leads to tolerization and decreased expression of the receptor in mammalian cells. We hypothesize that skewing cell death away from apoptosis using lipid A mimetics to lower TLR4 expression prior to UV exposure will reduce carcinogenic potential. To analyze the roll of TLR4 in UV-induced carcinogenesis, wildtype and TLR4-deficient bone marrow-derived macrophage (BMDM) cell lines were tolerized with hexa-acylated or penta-acylated lipid A from multiple Gram-negative species and exposed to either 10 or 25 mJ/cm 2doses of UVB radiation. UV-irradiated BMDM cells show evidence of apoptosis including cleavage of DNA creating a ladder, whereas UV-irradiated BMDM cells tolerized with lipid A mimetics show a lack of apoptosis. The data suggests that tolerization of TLR4 using canonical ligands may be a useful tool in promoting DNA repair and maintaining immune responses following UV-induced damage. The research was supported by a Fisher College of Science and Mathematics Undergraduate Research Grant.

307 Functional analysis of the genomic abnormalities of non uv-induced cutaneous squamous cell carcinomas

307 Functional analysis of the genomic abnormalities of non uv-induced cutaneous squamous cell carcinomas

Abstract 5188: Interrogating the role of the immune microenvironment in the response of brain metastases to immunotherapy using new preclinical melanoma models

Abstract Brain metastases (BrM) remain an intractable, deadly complication for advanced melanoma patients and efficient therapeutic strategies are desperately needed. The tumor microenvironment (TME) plays an important role in response to therapy. However, studies addressing the contribution of the TME to therapy efficacy for BrM are lacking, mostly due to limited access to human samples and scarcity of appropriate preclinical models. Here, we describe two novel isogenic immunocompetent BrM models generated by intracardiac injection of UV-induced mouse melanoma cell lines, representative of mutant-RAS human melanoma subtypes. We used these models to test immune checkpoint blockade (ICB) therapy and to interrogate the role of the TME in therapeutic efficacy. To evaluate response, we developed and applied a new machine-learning method to quantify metastatic burden. We investigated the TME by high-parametric flow cytometry and single-cell RNA sequencing (scRNA-seq). We showed that the models have distinct metastatic behaviors, with BR1 being mostly brain tropic and BR3 displaying widespread metastases. Notably, BR1 BrM were sensitive to ICB with a better response to anti-PD-L1/anti-CTLA-4 combination therapy as compared to monotherapies. In contrast, BR3 BrM were resistant to both mono- and combination therapies. Interestingly, we found that ICB efficacy on extracranial BR3 metastases is organ-dependent. Characterization of the BrM immune microenvironment before and after treatment revealed dramatic differences between the models. Untreated BR1 BrM showed significant recruitment of T cells, dendritic cells, and natural killer cells, while neutrophils were enriched in untreated ICB-resistant BR3 BrM. Moreover, we uncovered phenotypically distinct microglia populations exclusively present in ICB-sensitive BR1 BrM that positively correlated with T cell infiltration. Consistent with this finding, scRNA-seq showed upregulation of genes encoding for T cell-attracting chemokines and antigen presentation uniquely in the BR1-associated microglia. Post-treatment analysis of the brain TME highlighted beneficial changes induced by ICB in the responsive BR1 model, including increased recruitment of CD8 T cells with an activated phenotype, while a mild recruitment of exhausted T cells was observed in the resistant BR3 model. Altogether, our data emphasize the importance of interrogating the BrM TME to understand therapeutic response. Our unique BrM models, mirroring the diversity of ICB response observed in patients, provide a robust platform for the much-needed mechanistic studies to optimize BrM therapy. Deciphering the contribution of the newly identified BR1 BrM-associated microglia to ICB efficacy will be crucial to the identification of novel therapeutic targets. Citation Format: Amélie Lopès, Jessica Rappaport, Eva Pérez Guijarro, Quanyi Chen, Emily Wu, Isabella Church, April Huang, Jessica Bridge, Sung Chin, Cari Smith, Charli Gruen, Khiem C. Lam, Romina E. Araya, Antonella Sassano, Chi-Ping Day, Glenn Merlino, Romina S. Goldszmid. Interrogating the role of the immune microenvironment in the response of brain metastases to immunotherapy using new preclinical melanoma models. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5188.

Antiphotoaging and Skin-Protective Activities of Ardisia silvestris Ethanol Extract in Human Keratinocytes.

Ardisia silvestris is a traditional medicinal herb used in Vietnam and several other countries. However, the skin-protective properties of A. silvestris ethanol extract (As-EE) have not been evaluated. Human keratinocytes form the outermost barrier of the skin and are the main target of ultraviolet (UV) radiation. UV exposure causes skin photoaging via the production of reactive oxygen species. Protection from photoaging is thus a key component of dermatological and cosmetic products. In this research, we found that As-EE can prevent UV-induced skin aging and cell death as well as enhance the barrier effect of the skin. First, the radical-scavenging ability of As-EE was checked using DPPH, ABTS, TPC, CUPRAC, and FRAP assays, and a 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay was used to examine cytotoxicity. Reporter gene assays were used to determine the doses that affect skin-barrier-related genes. A luciferase assay was used to identify possible transcription factors. The anti-photoaging mechanism of As-EE was investigated by determining correlated signaling pathways using immunoblotting analyses. As-EE had no harmful effects on HaCaT cells, according to our findings, and As-EE revealed moderate radical-scavenging ability. With high-performance liquid chromatography (HPLC) analysis, rutin was found to be one of the major components. In addition, As-EE enhanced the expression levels of hyaluronic acid synthase-1 and occludin in HaCaT cells. Moreover, As-EE dose-dependently up-regulated the production of occludin and transglutaminase-1 after suppression caused by UVB blocking the activator protein-1 signaling pathway, in particular, the extracellular response kinase and c-Jun N-terminal kinase. Our findings suggest that As-EE may have anti-photoaging effects by regulating mitogen-activated protein kinase, which is good news for the cosmetics and dermatology sectors.

Exosomes from hypoxia-pretreated adipose-derived stem cells attenuate ultraviolet light-induced skin injury via delivery of circ-Ash1l.

An increasing number of studies have reported that exosomes from adipose-derived stem cells (ADSCs) have antioxidant and anti-inflammatory properties. In the present study, we aimed at elucidating the potential therapeutic mechanism underlying ADSC exosomes in ultraviolet B-light (UVB)-induced skin injury. We isolated the exosomes from ADSCs and hypoxia-pretreated ADSCs. High-throughput sequencing was applied to identify differential circRNA expression. Then, a UV-induced murine skin injury model was constructed and the therapeutic effect of exosomes was determined using immunofluorescence and ELISA. The regulatory mechanism was demonstrated using luciferase reporter analysis and an in vitro experiment. Exosomes from hypoxia-pretreated ADSCs inhibited UVB light-induced vascular injury by reversing ROS and inflammatory factor expression. High-throughput sequencing showed that exosomes from hypoxia-pretreated ADSCs (HExo) improved UV-induced skin damage via delivery of circ-Ash1l. Downregulation of circ-Ash1l inhibited the therapeutic effect of HExo on UV-induced skin damage. It was further shown that GPX4 and miR-700-5p were circ-Ash1l downstream targets. MiR-700-5p overexpression or GPX4 downregulation inhibited the circ-Ash1l protective effects of UV-induced endothelial progenitor cell (EPC) damage. Thus, exosomes from hypoxia-pretreated ADSCs attenuated UV light-induced skin injury via circ-Ash1l delivery and ferroptosis inhibition.

Protective effect of bromelain and pineapple extracts on UV-induced damage in human skin cells

In Hawaii, people experience high sunlight exposure, contributing to an increased risk of sunburn. Additionally, most parts of pineapples are discarded, contributing to food waste and microbial spoilage, and we wanted to determine whether bromelain sourced from pineapple could be repurposed as a treatment to protect skin cells from UV damage. Bromelain from pineapple can be used to treat symptoms of sunburn, which occurs when UV rays damage the DNA in cells. Therefore, we hypothesized that bromelain extracted from various parts of the pineapple (crown, flesh, skin, and stem) would protect the skin cells from cell death caused by UV damage. Also, we expected bromelain from the stem, which is known to contain the highest concentration of bromelain, to be the most effective in protecting skin cells from UV-induced cell death. The effect of purified bromelain powder on skin cell survival was analyzed using the PrestoBlue cell viability assay to compare the protective effect of pineapple extracts on UV-induced cell death. We also examined the expression level of tumor necrosis factor-α (TNF-α), which is a pro-inflammatory marker. The results indicated that bromelain protected skin cells from UV-dependent cell death and increased the mRNA expression level of TNF-α. Additionally, bromelain had a more protective effect when it was used as a pre-treatment method than post-treatment. Overall, this study suggests that bromelain may provide some protection to the skin from UV-induced cell death. Thus, further studies may investigate its application in sunscreen products to improve protection.

Sulphide Donor Exhibits Cytoprotective and Antioxidative Activity in UV-induced HaCaT Cell Lines

Oxidative stress due to excessive of reactive oxygen species (ROS) in the body is commonly associated as one of the underlying mechanisms of ultraviolet radiation (UV)-induced damage in the skin. Reactive sulphur species (RSS) has been implicated with potent antioxidant properties and involves in modulating cellular signalling transduction pathway. In this current study, the potential involvement of the RSS in alleviating UV-induced damage in HaCaT keratinocytes was explored. We first established the suitable dose of UVA and UVB radiation that can depressed HaCaT cells population, 80 mJ/cm2 and 10 mJ/cm2, respectively. The sulphide donor, NaHS, was also tested for its cytotoxicity profile, and 200 µM was considered non-toxic concentration for the cells. Our data showed that pre-treating the cells with 200 µM of NaHS decreased the detrimental effects of UV radiation especially UVA on HaCaT cells as demonstrated by the MTT assay. In this work, we used 2’,7’-dichlorofluorescin-diacetate (DCFH-DA), a useful indicator of ROS, with regard to the determining of antioxidant potential of NaHS. Our data demonstrate that 200 µM of NaHS significantly suppressed the intracellular ROS production induced by both UVA and UVB irradiation in comparison with cells absence of NaHS (p&lt;0.05). In conclusion, supplementation of sulphide in biological condition particularly NaHS provides protective effect for skin against UV irradiation by diminishing the formation of ROS. Nonetheless, this study provides a preliminary insight on the potential role of RSS in modulating UV-induced damages in in vitro skin model which can be further expand with precision technique in the future.

Protective effects of volatile components of aged garlic extract against ultraviolet B-induced apoptosis in human skin fibroblasts.

Aged garlic extract (AGE) has been shown to protect the skin against UV-induced damage, but effects of its volatile components remain unknown. We investigated the effects of the volatile fraction of AGE on the responses of cultured skin fibroblasts subjected to UV-B irradiation. UV-B irradiation (20 mJ/cm2 ) reduced the cell viability to 55% of control. The nonvolatile and volatile fractions of AGE inhibited the UV-B-induced reduction of cell viability; the cell viabilities were 100% and 73%, respectively. The volatile fraction inhibited the UV-B-induced increase in apoptotic cell death by 28%. The volatile fraction also inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) induced by UV-B irradiation. GC-MS analysis revealed that a large number of volatile compounds were generated during aging of garlic. These results suggest that the volatile fraction of AGE has protective effects against the UV-B-induced death of skin fibroblasts, and that this effect may partly be due to an inhibition of apoptosis via the downregulation of MAPK signaling. The volatile compounds of AGE may have beneficial applications for skin health. PRACTICAL APPLICATIONS: In this study, we investigated the effects of AGE against cell damage of UV-B-irradiated human skin fibroblasts. The aging process of garlic produced characteristic volatile compounds that have significant protective effects against UV-induced cell damage. Our results demonstrated that the aging process is a suitable method to develop added value in garlic extracts to improve skin health.