UVC222 nm has germicidal effects with potential clinical applications. However, UVC irradiation is capable of inducing DNA damage like cyclobutylpyrimidine dimers (CPD). Although new devices have emission peaks in the short‐wavelength region of UVC (~222 nm), the remaining “collateral” radiation at longer wavelengths could be harmful to human health. We investigated the DNA damage caused by far‐UVC 222 nm KrCl exciplex radiation on human skin reconstructs after additional filtering using silica filters. The skin reconstructs were irradiated with 100 mJ cm⁻², 500 mJ cm⁻², and 3 × 500 mJ cm⁻² unfiltered and filtered (230–270 nm suppressed) far‐UVC or UVB (308 nm) radiation. UVB and non‐filtered UVC irradiation induced a significant amount of CPDs, compared with the background. Filtered far‐UVC lowered the CPD amount compared with unfiltered UVC and UVB treatments. Repetitive UVC irradiation did not result in the accumulation of CPDs compared with UVB treatment. Reduction in excess of 99.9% of E. coli, S. aureus and C. albicans was detected after applying far‐UVC radiation. This identifies a therapeutic window in which microorganisms are killed but tissue is still alive and not damaged, which could give rise to new clinical applications.

The exposure to UVA (320–400 nm) irradiation is a major threat to human skin concerning photoaging and carcinogenesis. It has been shown that UVA irradiation can induce reactive oxygen species (ROS) and DNA mutations, such as 8-hydroxydeoxyguanosine. Furthermore, UVA induces the expression of photoaging-associated matrix metalloproteases (MMPs), especially of matrix metalloprotease 1 (MMP 1) and matrix metalloprotease 3 (MMP 3). In addition to this, it was recently shown that UVA-induced ROS also increase glucose metabolism of melanoma cells, however, the influence of UVA on the glucose metabolism of non-malignant cells of the human skin has, so far, not been investigated in detail. Here, we investigated the UVA-induced changes in glucose metabolism and the functional relevance of these changes in primary fibroblasts—normal non-malignant cells of the skin. These cells showed an UVA-induced enhanced glucose consumption and lactate production and changes in pyruvate production. As it has been proposed that pyruvate could have antioxidant properties we tested the functional relevance of pyruvate as protective agent against UVA-induced ROS. Our initial experiments support earlier publications, demonstrating that pyruvate treated with H₂O₂ is non-enzymatically transformed to acetate. Furthermore, we show that this decarboxylation of pyruvate to acetate also occurs upon UVA irradiation. In addition to this, we could show that in fibroblasts pyruvate has antioxidant properties as enhanced levels of pyruvate protect cells from UVA-induced ROS and partially from a DNA mutation by the modified base 8-hydroxydeoxyguanosine. Furthermore, we describe for the first time, that the interaction of UVA with pyruvate is relevant for the regulation of photoaging-associated MMP 1 and MMP 3 expression. Graphical abstract

The damaging effects of solar ultraviolet (UV) radiation exposure to human skin are well known and can reach from accelerated skin aging (photoaging) to skin cancer. Much of the damaging effects of solar UVA (320–400 nm) radiation is associated with the induction of reactive oxygen species (ROS), which are capable to cause oxidative damage to DNA like the oxidized guanosine 8-hydroxy-2' -deoxyguanosine (8-OHdG). Therefore, new UV protective strategies, have to be tested for their efficiency to shield against UV induced damage. We investigated the protective effects of HelioVital sun protection filter foil against UVA1 irradiation in skin cells. It could be shown, that HelioVital sun protection filter foil has protective effects against UVA1 irradiation induced changes in matrix metalloproteinase (MMP) expression. Furthermore a UVA1-dependant regulation of MMP15 in human fibroblasts could be shown for the first time in this context. In addition, this study demonstrated the protective effect of the HelioVital filter film against UVA1-induced ROS production and DNA damage. These results could pave the way for clinical studies with HelioVital filter foil shielding against the damaging effects of phototherapy and other forms of irradiation therapy, thereby increasing the safety and treatment opportunities of these forms of therapy. Graphical abstract

Background/Objectives: Actinic keratosis (AK) occurs on sun-damaged skin and is considered a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) and red light, is a common treatment for AK. However, its clinical efficacy for invasive tumors such as SCC is limited by the poor penetration and distribution of the photosensitizer. Cold atmospheric plasma (CAP), a partially ionized gas, increases skin permeability and exhibits anti-cancer properties through the generation of reactive oxygen species (ROS). In a previous study, CAP showed promising synergistic effects when combined with ALA-PDT for the treatment of SCC cells in vitro. The present study investigated the effects of combining CAP with ALA-PDT on cutaneous AK and SCC induced by ultraviolet B (UV-B) irradiation in SKH1 hairless mice. Methods: We compared various application sequences (CAP-ALA–red light, ALA–red light–CAP, and ALA-CAP–red light) against conventional ALA-PDT using visual, histological, and molecular assessments of the affected skin. Results: The results demonstrated that combined treatments strongly inhibited the growth of UV-B-induced skin lesions. TUNEL staining revealed increased apoptosis following both single and combined therapies, while Ki-67 staining indicated reduced keratinocyte proliferation and diminished DNA damage in treated areas. mRNA expression analysis showed the upregulation of apoptosis-related genes (p16^INK4a, p21^CIP1) alongside enhanced anti-tumor immune responses (IL-6, IL-8) in the affected tissue samples. Notably, the combined treatment enhances the therapeutic effect, whereas the sequence of application does not seem to be relevant for therapeutic efficacy in vivo. Conclusions: Overall, these results suggest that CAP may enhance the anti-tumor effect of conventional ALA-PDT, supporting previous findings on SCC cells.

Background/Objectives: Studying the role of UV-induced metabolic changes in skin physiology, and especially skin diseases, has gained importance in both medicine and cosmetics. With the development of new technologies, a variety of approaches have been implemented to model these metabolic effects. In this study, we explore the reproducibility of the UVA1-induced metabolic changes observed in different in vitro, ex vivo, and in vivo systems with escalating complexity. Our aim is to elaborate on the role of experimental setups in the reliable representation of in vivo data in other systems. Methods: Metabolic profiles post UVA1 treatment were assessed in skin cell culture, skin explants, and intact skin. For cell culture and explants, the metabolites from the culture medium were assessed via 1D-CPMG NMR. Intact skin samples were collected via microdialysis and the resulting dialysate was measured with GC–TOF-MS. Results: Data show that, despite great metabolic variations between the systems, several metabolites, such as glutamic acid, succinic acid, and threonine, change in a similar manner across multiple systems after UVA1 irradiation, including in vivo settings. Some metabolites, like phenylalanine, citric acid, and pyruvic acid, show similar UVA-mediated metabolic patterns between corresponding in vitro and ex vivo systems, but do not overlap well with in vivo data. Conclusions: Our findings emphasize the need for a metabolite-by-metabolite approach when deciding on the proper experimental system to perform UV irradiation experiments with regard to cutaneous physiology.