Photoallergic Research Articles

Phototoxic Effects on Skin Biomolecules Induced by a Domestic Nail Polish Dryer Device.

UVA radiation and visible light can lead to indirect damage to DNA, proteins, and lipids through photosensitized reactions, where a molecule undergoes a photochemical alteration by the initial absorption of radiation by another molecular entity called photosensitizer (Sens). The chemical changes undergone by biomolecules in photosensitized reactions can trigger important adverse processes such as photoallergy, phototoxicity, and skin cancer, among others. Despite the knowledge about photosensitized reactions and the fact that many endogenous compounds present in the skin can act as Sens, UVA, and visible light are widely used in several devices for domestic and general use without a thorough evaluation of their possible harmful effects; one prominent example is UV-nail polish dryers. The information in the literature about the possible damage that can be caused by using this type of radiation source is controversial. In this work, we demonstrate that the radiation dose emitted by the nail polish dryer device during a typical gel nail manicure session effectively degrades molecules present in the skin under physiological and pathological conditions. Additionally, it may induce damage to biomolecules such as proteins and lipids due to the photosensitization process, leading to the loss of their biological functions.

Cutaneous adverse events associated with BRAF and MEK inhibitors: a systematic review and meta-analysis.

Cutaneous adverse events (CAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. To determine the association of BRAF and MEK inhibitor treatment with CAEs in patients with melanoma compared with BRAF inhibitor alone. PubMed, Cochrane, Embase and Web of Science were systematically searched for BRAF and MEK inhibitors from database inception through 10 May 2024. Randomized clinical trials reporting on CAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected. Pooled Risk ratios (RRs) and 95% CIs were determined using random-effects analyses. The selected end points were alopecia, cutaneous squamous-cell carcinoma, hyperkeratosis, keratoacanthoma, palmoplantar erythrodysaesthesia syndrome, palmoplantar keratoderma, rash, photosensitivity reaction, and skin papilloma. All-grade and high-grade (≥3) CAEs were recorded. Comparing with BRAF and MEK inhibitors, treatment with BRAF inhibitors alone was associated with an increased risk of rash (RR, 0.73; 95% CI, 0.54-0.99; p = 0.039; I2 = 88%), alopecia (RR, 0.28; 95% CI, 0.20-0.41; P < 0.001; I2 = 76%), hyperkeratosis (RR, 0.30; 95% CI, 0.22-0.41; P < 0.001; I2 = 56%), palmoplantar erythrodysaesthesia syndrome (RR, 0.21; 95% CI, 0.10-0.47; P < 0.001; I2 = 81%), palmoplantar keratoderma (RR, 0.39; 95% CI, 0.26-0.57; P < 0.001; I2 = 29%), Skin papilloma (RR, 0.25; 95% CI, 0.12-0.52; P < 0.001; I2 = 77%), cutaneous squamous-cell carcinoma (RR, 0.21; 95% CI, 0.11-0.42; P < 0.001; I2 = 50%), and keratoacanthoma (RR, 0.22; 95% CI, 0.12-0.40; P < 0.001; I2 = 0%). Therapy with BRAF and MEK inhibitors was associated with a lower risk of CAEs, especially rash, alopecia, hyperkeratosis, palmoplantar erythrodysaesthesia syndrome, palmoplantar keratoderma, skin papilloma, cutaneous squamous-cell carcinoma, and keratoacanthoma, compared with BRAF inhibitor alone. The risks of photosensitivity reaction was similar between the assessed groups. The findings may help to balance between beneficial melanoma treatment and cutaneous morbidity and mortality.

The Use of Fluorescent Markers to Detect and Delineate Head and Neck Cancer: A Scoping Review.

The aim of surgery for head and neck squamous cell carcinoma (HNSCC) is to achieve clear resection margins, whilst preserving function and cosmesis. Fluorescent markers have demonstrated potential in the intraoperative visualisation and delineation of tumours, such as glioma, with consequent improvements in resection. The purpose of this scoping review was to identify and compare the fluorescent markers that have been used to detect and delineate HNSCC to date. A literature search was performed using the Ovid MEDLINE, Ovid Embase, Cochrane CENTRAL, ClinicalTrials.gov and ICTRP databases. Primary human studies published through September 2023 demonstrating the use of fluorescent markers to visualise HNSCC were selected and reviewed independently by two authors. The search strategy identified 5776 records. Two hundred and forty-four full texts were reviewed, and sixty-five eligible reports were included. The most used fluorescent markers in the included studies were indocyanine green (ICG) (n = 14), toluidine blue (n = 11), antibodies labelled with IRDye800CW (n = 10) and 5-aminolevulinic acid (5-ALA) (n = 8). Toluidine blue and ICG both have limited specificity, although novel targeted options derived from ICG may be more effective. 5-ALA has been demonstrated as a topical marker and, recently, via enteral administration but it is associated with photosensitivity reactions. The fluorescently labelled antibodies cetuximab-IRDye800CW and panitumumab-IRDye800CW are promising options being investigated by ongoing trials. Multiple safe fluorescent markers have emerged which may aid the surgical resection of HNSCC. Further research in larger cohorts is required to identify which marker should be considered gold standard.

462 Violet light at 405 nm promotes photo-damage through the photosensitization reaction of carbonylated proteins

462 Violet light at 405 nm promotes photo-damage through the photosensitization reaction of carbonylated proteins

Photosensitizing Properties of the Topical Retinoid Drug Adapalene.

Photoreactivity is an important issue for topical drugs especially when these are applied on the sun-exposed skin area. In this context, third-generation retinoids are of special interest due to their conjugated chemical structure and their use in the treatment of acne. Herein, the phototoxic potential of one of these drugs, adapalene, is established using an in vitro 3T3 Neutral Red Uptake (NRU) test. Photophysical studies demonstrate the involvement of a Type II process with an efficient formation of singlet oxygen. Interestingly, quenching of the adapalene singlet manifold by oxygen leads to an increased production of this reactive oxygen species through the tagged O2-enhanced intersystem crossing process. Taken together, these results are relevant from a toxicological point of view as adapalene could be considered as a double-edged sword: it can be at the origin of undesired skin photosensitivity reactions or be considered as a candidate for topical photodynamic therapy.

An In Vitro Strategy to Evaluate Ketoprofen Phototoxicity at the Molecular and Cellular Levels.

Phototoxicity is a significant problem that occurs in a large part of the population and is often caused by commonly used pharmaceuticals, including over-the-counter drugs. Therefore, testing drugs with photosensitizing potential is very important. The aim of this study is to analyze the cytotoxicity and phototoxicity of ketoprofen towards human melanocytes and fibroblasts in three different treatment schemes in order to optimize the study. Cytometric tests (studies of viability, proliferation, intracellular thiol levels, mitochondrial potential, cell cycle, and DNA fragmentation), Western blot analysis (cytochrome c and p44/p42 protein levels), and confocal microscopy imaging were performed to assess the impact of the developed treatments on skin cells. Research on experimental schemes may help reduce or eliminate the risk of phototoxic reactions. In the case of ketoprofen, we found that the strongest phototoxic potential was exhibited in the treatment where the drug was present in the solution during the irradiation of cells, both pigmented and non-pigmented cells. These results indicate that the greatest risk of photosensitivity reactions related to ketoprofen occurs after direct contact with the drug and UV exposure.

The Potential of Natural Compounds in UV Protection Products.

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.

Cardiodermatology: the heart of the connection between the skin and cardiovascular disease.

The skin and cardiovascular systems are connected in unique and meaningful ways, and many diseases conventionally considered as being limited to one organ system are more closely related than previously believed. Major cardiovascular diseases and phenomena such as infective endocarditis, congestive heart failure, Kawasaki disease and thromboembolism are associated with specific skin findings, and advances in genetics, immunology and clinical epidemiology show that inflammatory dermatological diseases, such as psoriasis, have serious cardiovascular and cardiometabolic consequences. Additionally, commonly used cardiovascular therapies, such as antihypertensive medications, are associated with important cutaneous adverse effects, including photosensitivity, photocarcinogenesis and eczematous skin reactions. Moreover, systemic dermatological therapies, including retinoids, Janus kinase inhibitors and biologics, can alter the risk of cardiovascular and cardiometabolic diseases. In this Review on cardiodermatology, we provide interdisciplinary insights from dermatology and cardiology that will be of practical use to both cardiologists and generalists who manage cardiovascular and cardiometabolic diseases in patients with dermatological findings or histories. We discuss specific skin findings associated with cardiovascular diseases to aid in diagnosis; important cutaneous adverse effects of common cardiovascular therapies, for the purpose of treatment monitoring; and the effect of dermatological diseases and dermatological treatment on cardiovascular risk.

Photoprotection and its implications for drug safety

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.

Photooxidation of Nonanoic Acid by Molecular and Complex Environmental Photosensitizers.

Photochemical aging and photooxidation of atmospheric particles play a crucial role in both the chemical and physical processes occurring in the troposphere. In particular, the presence of organic chromophores within atmospheric aerosols can trigger photosensitized oxidation that drives the atmospheric processes in these interfaces. However, the light-induced oxidation of the surface of atmospheric aerosols, especially those enriched with organic components, remains poorly understood. Herein, we present a gravimetric and vibrational spectroscopy study aimed to investigate the photosensitized oxidation of nonanoic acid (NA), a model system of fatty acids within organic aerosols, in the presence of complex organic photosensitizers and molecular proxies. Specifically, this study shows a comparative analysis of the photosensitized reactions of thin films containing nonanoic acid and four different organic photosensitizers, namely marine dissolved organic matter (m-DOM) and humic acids (HA) as environmental photosensitizers, and 4-imidazolecarboxaldehyde (4IC) and 4-benzoylbenzoic acid (4BBA) as molecular proxies. All reactions show predominant photooxidation of nonanoic acid, with important differences in the rate and yield of product formation depending on the photosensitizer. Limited changes were observed in the organic photosensitizer itself. Results show that, among the photosensitizers examined, 4BBA is the most effective in photooxidizing nonanoic acid. Overall, this work underscores the role of chromophores in the photooxidation of organic thin films and the relevance of such reactions on the surface of aerosols in the marine environment.

Supramolecular Reconstruction of Self-Assembling Photosensitizers for Enhanced Photocatalytic Hydrogen Evolution.

Natural photosynthetic systems require spatiotemporal organization to optimize photosensitized reactions and maintain overall efficiency, involving the hierarchical self-assembly of photosynthetic components and their stabilization through synergistic interactions. However, replicating this level of organization is challenging due to the difficulty in efficiently communicating supramolecular nano-assemblies with nanoparticles or biological architectures, owing to their dynamic instability. Herein, we demonstrate that the supramolecular reconstruction of self-assembled amphiphilic rhodamine B nanospheres (RN) through treatment with metal-phenolic coordination complexes results in the formation of a stable hybrid structure. This reconstructed structure enhances electron transfer efficiency, leading to improved photocatalytic performance. Due to the photoluminescence quenching property of RN and its electronic synergy with tannic acid (T) and zirconium (Z), the supramolecular complexes of hybrid nanospheres (RNTxZy) with Pt nanoparticles or a biological workhorse, Shewanella oneidensis MR-1, showed marked improvement in photocatalytic hydrogen production. The supramolecular hybrid particles with a metal-phenolic coordination layer showed 5.6- and 4.0-fold increases, respectively, in the productivities of hydrogen evolution catalyzed by Pt (Pt/RNTxZy) and MR-1 (M/RNTxZy), respectively. These results highlight the potential for further advancements in the structural and photochemical control of supramolecular nanomaterials for energy harvesting and bio-hybrid systems.

Supramolecular Reconstruction of Self‐Assembling Photosensitizers for Enhanced Photocatalytic Hydrogen Evolution

Natural photosynthetic systems require spatiotemporal organization to optimize photosensitized reactions and maintain overall efficiency, involving the hierarchical self‐assembly of photosynthetic components and their stabilization through synergistic interactions. However, replicating this level of organization is challenging due to the difficulty in efficiently communicating supramolecular nano‐assemblies with nanoparticles or biological architectures, owing to their dynamic instability. Herein, we demonstrate that the supramolecular reconstruction of self‐assembled amphiphilic rhodamine B nanospheres (RN) through treatment with metal‐phenolic coordination complexes results in the formation of a stable hybrid structure. This reconstructed structure enhances electron transfer efficiency, leading to improved photocatalytic performance. Due to the photoluminescence quenching property of RN and its electronic synergy with tannic acid (T) and zirconium (Z), the supramolecular complexes of hybrid nanospheres (RNTxZy) with Pt nanoparticles or a biological workhorse, Shewanella oneidensis MR‐1, showed marked improvement in photocatalytic hydrogen production. The supramolecular hybrid particles with a metal‐phenolic coordination layer showed 5.6‐ and 4.0‐fold increases, respectively, in the productivities of hydrogen evolution catalyzed by Pt (Pt/RNTxZy) and MR‐1 (M/RNTxZy), respectively. These results highlight the potential for further advancements in the structural and photochemical control of supramolecular nanomaterials for energy harvesting and bio‐hybrid systems.

Drug-induced photosensitivity associated with anticancer therapies.

Despite the promising results in terms of effectiveness of anticancer treatments, a wide range of dermatologic adverse reactions have been reported. Among them, skin photosensitivity, defined as a range of dermatologic conditions caused or exacerbated by sunlight exposure, is an emerging adverse event. A review of the current literature was performed to report the most characteristic phototoxic and photoallergic reactions associated with anticancer therapies, as well as other characteristic manifestations potentially related to photo-exposure, including UV recall, vitiligo-like reactions, drug-induced cutaneous lupus erythematosus, and UV-induced hyperpigmentation. A total of 30 manuscripts were collected in the present review, reporting several phototoxic and photoallergic reactions associated with anticancer therapies. Photosensitivity reactions are an increasing challenge in cancer management. The raising awareness about this adverse event has increased the identification of potential photosensitizing drugs as well as its prevention and the management. However, more studies are required to improve the knowledge of this cutaneous toxicity and to define a personalized treatment strategy.

Pirfenidone as a Cornerstone in the Management of Fibrotic Interstitial Lung Diseases and Its Emerging Applications: A Comprehensive Review.

Pirfenidone is a groundbreaking antifibrotic agent that has become a cornerstone in managing fibrotic interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF). This review comprehensively analyzes pirfenidone's mechanisms of action, clinical efficacy, safety profile, and emerging applications beyond IPF. Pirfenidone exerts its therapeutic effects by inhibiting key pathways involved in fibrosis, including transforming growth factor-beta (TGF-β) and other pro-fibrotic cytokines. It also reduces oxidative stress and inflammation. Clinical trials have consistently demonstrated pirfenidone's ability to slow the decline in lung function, reduce disease progression, and improve survival rates in IPF patients. Furthermore, emerging evidence supports its potential use in other fibrotic ILDs and non-pulmonary fibrotic conditions, such as liver and kidney fibrosis. Despite its proven benefits, pirfenidone's safety and tolerability profiles require careful monitoring, with gastrointestinal and photosensitivity reactions being the most common adverse effects. Future research is poised to explore combination therapies, personalized treatment approaches, and novel applications of pirfenidone in a broader range of fibrotic disorders. As the field of antifibrotic therapy advances, pirfenidone remains a pivotal agent with the potential to significantly impact the management of fibrotic diseases across multiple organ systems. This review aims to provide clinicians and researchers with a detailed understanding of pirfenidone's current role and prospects in treating fibrosis.

Surprising results of patch testing with the baseline series in patients with photocontact allergy to ketoprofen.

Photoallergic reactions due to topical ketoprofen are common. As some simultaneous contact allergies have been described in the literature, we aimed to get an overview of the pattern of reactivity towards common allergens in the baseline series in ketoprofen-photoallergic individuals. Using our database, we found 94 patients with photocontact allergy to ketoprofen diagnosed during 1999-2018. Approximately 12 800 patients patch tested with the baseline series during the same time frame served as controls. Data on patch testing with the baseline series of 518 individuals belonging to the general population were obtained from an earlier study, and a comparison of allergy rates was made with the ketoprofen group. Contact allergy to fragrance mix I and Myroxylon pereirae was overrepresented among patients with photocontact allergy to ketoprofen (42.3% vs. 6.6% and 47.9% vs. 6.6%, p < 0.001, respectively). Significant overrepresentation was also shown for 4-tert-butylphenolformaldehyde resin (PTBP-F-R), phenol formaldehyde resin (PFR-2), black rubber mix, budesonide (all p < 0.001), and fragrance mix II (p = 0.02). The pattern was similar, but with lower significance levels for fragrance mix II and budesonide, regardless of whether or not the individuals had been photopatch tested because of a suspected photoallergic contact dermatitis from ketoprofen. Contact allergy to fragrance mix I, Myroxylon pereirae, black rubber mix, PFR-2, PTBP-FR, and to a somewhat lower extent, to fragrance mix II and budesonide, is common in individuals photoallergic to ketoprofen. It remains to be seen whether sensitisation to ketoprofen leads to simultaneous sensitisation to a number of other, chemically non-related, substances.

Cellular damage photosensitized by dasatinib, radical-mediated mechanisms and photoprotection in reconstructed epidermis

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 (3DAS∗) 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.

Based on network pharmacology, molecular docking and experimental verification to reveal the mechanism of Andrographis paniculata against solar dermatitis

BackgroundSolar 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. PurposeThis 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. MethodsAP-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. ResultsThere 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. ConclusionThe 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.

A hyaluronic acid-based dissolving microneedle patch loaded with 5-aminolevulinic acid for improved oral leukoplakia treatment

IntroductionA local microneedle patch loaded with 5-aminolevulinic acid (ALA) was constructed to improve the efficiency of ALA photodynamic treatment of oral leukoplakia, reduce local photosensitivity reactions, and promote the healing of lesions. MethodsThe microneedle patch loaded with ALA was constructed with the hyaluronic acid (HA) solution (ALA-HAMN), and its morphology, strength, mucosal penetration, and biocompatibility were tested. ResultsIn vivo safety and permeability tests confirmed that ALA-HAMN had good biocompatibility and could penetrate the mucosal barrier and quickly dissolve and release ALA for in situ transdermal administration. The 4-nitroquinoline oxide (NQO) rat model experiment showed that ALA-HAMN can significantly improve photodynamic therapy (PDT) efficiency and has no damage to mucosal tissue compared with the commonly used ALA cotton ball dressing. ConclusionsThe ALA-loaded microneedle patch was successfully constructed for the photodynamic treatment of oral leukoplakia, and the photodynamic efficiency and comfort of oral leukoplakia were improved, which provided an effective delivery mode to improve clinical ALA-PDT treatment of oral leukoplakia (OLK).

Synergistic Toxicity of Pollutant and Ultraviolet Exposure from a Mitochondrial Perspective.

Ultraviolet (UV) exposure and atmospheric pollution are both independently implicated in skin diseases such as cancer and premature aging. UVA wavelengths, which penetrate in the deep layers of the skin dermis, exert their toxicity mainly through chromophore photosensitization reactions. Benzo[a]pyrene (BaP), the most abundant polycyclic aromatic hydrocarbon originating from the incomplete combustion of organic matter, could act as a chromophore and absorb UVA. We and other groups have previously shown that BaP and UVA synergize their toxicity in skin cells, which leads to important oxidation. Even if mitochondria alterations have been related to premature skin aging and other skin disorders, no studies have focused on the synergy between UV exposure and pollution on mitochondria. Our study aims to investigate the combined effect of UVA and BaP specifically on mitochondria in order to assess the effect on mitochondrial membranes and the consequences on mitochondrial activity. We show that BaP has a strong affinity for mitochondria and that this affinity leads to an important induction of lipid peroxidation and membrane disruption when exposed to UVA. Co-exposure to UVA and BaP synergizes their toxicity to negatively impact mitochondrial membrane potential, mitochondrial metabolism and the mitochondrial network. Altogether, our results highlight the implication of mitochondria in the synergistic toxicity of pollution and UV exposure and the potential of this toxicity on skin integrity.

Targeting non-classical autophagy-dependent ferroptosis and the subsequent HMGB1/TfR1 feedback loop accounts for alleviating solar dermatitis by senkyunolide I

Given the substantial risks associated with ultraviolet B (UVB) radiation-induced solar dermatitis, enhancing current strategies to combat UVB regarding skin diseases is imperative. The cross-talk between ferroptosis and inflammation has been proven to be an essential factor in UVB-induced solar dermatitis, whereas detailed process of how their interaction contributes to this remains unclear. Therefore, further investigation of ferroptosis-mediated processes and identification of corresponding inhibitory approaches hold promise for repairing skin damage. Senkyunolide I (Sen I), a bioactive component mainly extracted from the traditional Chinese medicinal plants, Ligusticum chuanxiong Hort. and Angelica sinensis (Oliv.) Diels, has demonstrated efficacy in combating oxidative stress and inflammation. In this study, we utilized UVB-irradiated HaCaT cells as an in vitro model and C57BL/6J mice as an in vivo model of solar dermatitis. Our findings revealed the pivotal roles of autophagy and ferroptosis in inducing skin inflammation, particularly emphasizing the activation of ferroptosis through macroautophagy. Surprisingly, this mechanism operated independently of ferritinophagy, a classical autophagy-driven ferroptosis pathway. Instead, our results highlighted Transferrin Receptor 1 (TfR1), tightly controlled by autophagy, as a crucial mediator of ferroptosis execution and amplifier of subsequent lethal signals. Furthermore, extracellular High Mobility Group Box 1 protein (HMGB1), released following UVB-induced ferroptotic cells from activated autophagic flux, initiated a feedback loop with TfR1, propagating ferroptosis to neighboring cells and exacerbating damage. Remarkably, Sen I administration showed a significant protective effect against UVB damage in both in vitro and in vivo models by interrupting this cascade. Consequently, we have illuminated a novel therapeutic pathway post-UVB exposure and identified Sen I as a potent natural molecule that safeguarded against UVB-induced solar dermatitis by suppressing the autophagy-ferroptosis-HMGB1-TfR1 axis, highlighting a new frontier in photoprotection.