Effects of Ultraviolet A-1 Radiation on Calcineurin Activity and Cytokine Production in (Skin) Cell Cultures†

Calcineurin (Cn) is the target of immunosuppressive drugs used for maintenance therapy of transplant patients. UV radiation is also known to be immunosuppressive and, like the Cn inhibitors, UV has been shown to positively influence various inflammatory skin diseases. Recently, Cn activity has been demonstrated in skin and skin cell cultures. In the present study we have investigated the effects of UV(A-1) irradiation on Cn activity in skin. In total skin we found a significant reduction in Cn activity after exposure to 450 kJ m⁻² of UVA-1 (340–400 nm). In repeated experiments cultures of fibroblasts and keratinocytes also showed dose-dependent and selective reduction in Cn activity after UVA-1 irradiation. UVB irradiation caused a decrease in the Cn activity of one of two fibroblast cultures and was ineffective in keratinocytes. In Jurkat cells and PBMC UVA-1 reduced Cn activity and also the production of cytokines such as interleukin (IL)-2, γ-interferon, IL-4 and IL-10 that are controlled by the Ca²⁺–Cn pathway. These results indicate that UV(A-1) irradiation may lead to inactivation of Cn in the skin and thus suppress the skin immune system in a similar fashion to the Cn inhibitors.     

Ultraviolet Light,Unfolded Protein Response and Autophagy†

The endoplasmic reticulum (ER) plays an important role in the regulation of protein synthesis. Alterations in the folding capacity of the ER induce stress, which activates three ER sensors that mediate the unfolded protein response (UPR). Components of the pathways regulated by these sensors have been shown to regulate autophagy. The last corresponds to a mechanism of self-eating and recycling important for proper cell maintenance. Ultraviolet radiation (UV) is an external damaging stimulus that is known for inducing oxidative stress, and DNA, lipid and protein damage. Many controversies exist regarding the role of UV-inducing ER stress or autophagy. However, a connection between the three of them has not been addressed. In this review, we will discuss the contradictory theories regarding the relationships between UV radiation with the induction of ER stress and autophagy, as well as hypothetic connections between UV, ER stress and autophagy.     

Ultraviolet Radiation Exposure and its Impacts on Cutaneous Phosphorylation Signaling in Carcinogenesis: Focusing on Protein Tyrosine Phosphatases†

Sunlight exposure is a significant risk factor for UV-induced deteriorating transformations of epidermal homeostasis leading to skin carcinogenesis. The ability of UVB radiation to cause melanoma, as well as basal and squamous cell carcinomas, makes UVB the most harmful among the three known UV ranges. UVB-induced DNA mutations and dysregulation of signaling pathways contribute to skin cancer formation. Among various signaling pathways modulated by UVB, tyrosine phosphorylation signaling which is mediated by the action of protein tyrosine kinases (PTKs) on specific tyrosine residues is highly implicated in photocarcinogenesis. Following UVB irradiation, PTKs get activated and their downstream signaling pathways contribute to photocarcinogenesis by promoting the survival of damaged keratinocytes and increasing cell proliferation. While UVB activates oncogenic signaling pathways, it can also activate tumor suppressive signaling pathways as initial protective mechanisms to maintain epidermal homeostasis. Tyrosine dephosphorylation is one of the protective mechanisms and is mediated by the action of protein tyrosine phosphatases (PTPs). PTP can counteract UVB-mediated PTK activation and downregulate oncogenic signaling pathways. However, PTPs have not been studied extensively in photocarcinogenesis with previous studies regarding their inactivation induced by UVB. This current review will summarize the recent progress in the protective function of PTPs in epidermal photocarcinogenesis.     

Sex as a Risk Factor for Solar Ultraviolet Radiation Exposure?–Dosimetry in Danish Outdoor Workers

Solar ultraviolet radiation (UVR) exposure is a known risk factor for the development of skin cancer. Heterogeneity in solar UVR exposure may explain the diversity in skin cancer incidence between men and women. This, however, has not previously been investigated in Danish outdoor workers using UVR dosimetry. The aim of this study was to evaluate sex differences in solar UVR dosimetry in Danish outdoor workers on working and leisure days. A cross-sectional design was used to collect dosimetry data during the Danish summer season (May to September). Analysis was based on an electronic questionnaire and dosimetry data from 450 outdoor workers (88 women, 362 men). Dosimetry data were reported as standard erythema dose (SED). The daily median SED (Interquartile range) on working days was 1.6 (2.5) in men and 1.5 (2.1) in women while on leisure days it was 0.5 (1.4) in men and 0.6 (1.3) in women. Analysis by multiple linear regression did not show any association between daily median SED and sex on either working or leisure days. In conclusion, solar UVR exposure in Danish outdoor workers did not vary according to sex.     

Trichloroisocyanuric Acid,A Swimming Pool Disinfectant: New Developments and Role in UV-Induced Skin Inflammation†

This article is a highlight of the paper by Snell et al. in the current issue of Photochemistry and Photobiology (Snell et al. Photochem. Photobiol. 2022). The authors utilized an organotypic human skin model and transgenic SKH-1 mice to determine the oxidative stress response induced by topical treatment of trichloroisocyanuric acid (TCIC), a common disinfectant used in swimming pool. Additionally, they determined molecular mechanisms associated with topical TCIC pretreatment followed by ultraviolet (UV) radiation exposure. This work provides the first example that cutaneous delivery of TCIC significantly increases UV-induced skin inflammation, suggesting a previously unidentified potential of TCIC. If translatable to human skin, these findings could be important for human skin health implications.     

Recent Photosensitizer Developments,Delivery Strategies and Combination-based Approaches for Photodynamic Therapy†

Photodynamic therapy of cancer (PDT) is a therapeutic technique, minimally invasive, which is currently used to treat cancerous lesions and tumors that have been in the spotlight for its potential over the recent decades. Nonetheless, PDT still needs further development to become a first-option treatment for patients. This review compiles recent progress in several aspects of the current research in the constantly growing area of PDT to overcome the main challenges as an attempt to serve as a guide and reference for newcomers into this research area. This review has been prepared to highlight the use of chemical modifications on photosensitizers to improve their solubility, photostability, selectivity and phototoxicity. Additionally, the use of liposomes and cavitands as drug delivery systems to aid in the biodistribution and bioaccumulation of photosensitizers is presented. Also, the combination of PDT with chemotherapy or immunotherapy as an option to boost and improve treatment outcomes is discussed. Finally, the inhibition of antioxidant enzymes as a strategy for a synergistic effect to ameliorate the performance of the photosensitizers in PDT is presented as an alternative for future researchers.     

No Evidence of Induced Skin Cancer or Other Skin Abnormalities after Long-Term (66 week) Chronic Exposure to 222-nm Far-UVC Radiation

Far-UVC radiation, typically defined as 200–235 nm, has similar or greater anti-microbial efficacy compared with conventional 254-nm germicidal radiation. In addition, biophysical considerations of the interaction of far-UVC with tissue, as well as multiple short-term safety studies in animal models and humans, suggest that far-UVC exposure may be safe for skin and eye tissue. Nevertheless, the potential for skin cancer after chronic long-term exposure to far-UVC has not been studied. Here, we assessed far-UVC induced carcinogenic skin changes and other pathological dermal abnormalities in 96 SKH-1 hairless mice of both sexes that were exposed to average daily dorsal skin doses of 400, 130 or 55 mJ cm⁻² of 222 nm far-UVC radiation for 66 weeks, 5 days per week, 8 h per day, as well as similarly-treated unexposed controls. No evidence for increased skin cancer, abnormal skin growths or incidental skin pathology findings was observed in the far-UVC-exposed mice. In addition, there were no significant changes in morbidity or mortality. The findings from this study support the long-term safety of long-term chronic exposure to far-UVC radiation, and therefore its potential suitability as a practical anti-microbial approach to reduce airborne viral and bacterial loads in occupied indoor settings.     

Photochemical Targeting of Mitochondria to Overcome Chemoresistance in Ovarian Cancer †

Ovarian cancer is the most lethal gynecologic malignancy with a stubborn mortality rate of ~65%. The persistent failure of multiline chemotherapy, and significant tumor heterogeneity, has made it challenging to improve outcomes. A target of increasing interest is the mitochondrion because of its essential role in critical cellular functions, and the significance of metabolic adaptation in chemoresistance. This review describes mitochondrial processes, including metabolic reprogramming, mitochondrial transfer and mitochondrial dynamics in ovarian cancer progression and chemoresistance. The effect of malignant ascites, or excess peritoneal fluid, on mitochondrial function is discussed. The role of photodynamic therapy (PDT) in overcoming mitochondria-mediated resistance is presented. PDT, a photochemistry-based modality, involves the light-based activation of a photosensitizer leading to the production of short-lived reactive molecular species and spatiotemporally confined photodamage to nearby organelles and biological targets. The consequential effects range from subcytotoxic priming of target cells for increased sensitivity to subsequent treatments, such as chemotherapy, to direct cell killing. This review discusses how PDT-based approaches can address key limitations of current treatments. Specifically, an overview of the mechanisms by which PDT alters mitochondrial function, and a summary of preclinical advancements and clinical PDT experience in ovarian cancer are provided.     

Photodynamic Priming Overcomes Per- and Polyfluoroalkyl Substance (PFAS)-Induced Platinum Resistance in Ovarian Cancer†

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants linked to adverse outcomes, including for female reproductive biology and related cancers. We recently reported, for the first time, that PFAS induce platinum resistance in ovarian cancer, potentially through altered mitochondrial function. Platinum resistance is a major barrier in the management of ovarian cancer, necessitating complementary therapeutic approaches. Photodynamic therapy (PDT) is a light-based treatment modality that reverses platinum resistance and synergizes with platinum-based chemotherapy. The present study is the first to demonstrate the ability of photodynamic priming (PDP), a low-dose, sub-cytotoxic variant of PDT, to overcome PFAS-induced platinum resistance. Comparative studies of PDP efficacy using either benzoporphyrin derivative (BPD) or 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) were conducted in two human ovarian cancer cell lines (NIH:OVCAR-3 and Caov-3). BPD and PpIX are clinically approved photosensitizers that preferentially localize to, or are partly synthesized in, mitochondria. PDP overcomes carboplatin resistance in PFAS-exposed ovarian cancer cells, demonstrating the feasibility of this approach to target the deleterious effects of environmental contaminants. Decreased survival fraction in PDP + carboplatin treated cells was accompanied by decreased mitochondrial membrane potential, suggesting that PDP modulates the mitochondrial membrane, reducing membrane potential and re-sensitizing ovarian cancer cells to carboplatin.     

Expression and Function of Macrophage Migration Inhibitory Factor in the Pathogenesis of UV-Induced Cutaneous Nonmelanoma Skin Cancer(†)

Chronic skin exposure to ultraviolet light stimulates the production of cytokines known to be involved in the initiation of skin cancer. Recent studies in mouse models suggested a role for macrophage migration inhibitory factor (MIF) in the UVB‐induced pathogenesis of nonmelanoma skin cancer (NMSC). Our studies aimed at defining the pathophysiological function of MIF in cutaneous inflammatory reactions and in the development and progression of NMSC. Immunohistochemical analysis revealed a moderate expression of MIF in normal human skin samples but an enhanced expression of this cytokine in lesional skin of patients with actinic keratosis or cutaneous SCC. Enzyme‐linked immunosorbent assay studies showed a time‐dependent increase in MIF secretion after a moderate single‐dose UVB irradiation in NHEKs and SCC tumor cells. MIF is known to interact with CXCR2, CXCR4 and CD74. These receptors are not constitutively expressed in keratinocytes and HaCaT cells and their expression is not induced by UVB irradiation either. However, stimulation with IFNγ upregulated CD74 surface expression in these cells. Affymetrix^® Gene Chip analysis revealed that only keratinocytes prestimulated with IFNγ are responsive to MIF. These findings indicate that MIF may be an important factor in the pathogenesis of NMSC tumorigenesis and progression in an inflammatory environment.     

A Five‐year Study of Solar Ultraviolet Radiation in Southern Chile (39° S): Potential Impact on Physiology of Coastal Marine Algae?

This study reports 5 years of (1998-2003) data on continuous solar-irradiation measurements from a scanning spectroradiometer (SUV-100) in Valdivia, Chile (39 degrees S), accompanied by evaluation of the impact of ultraviolet radiation (UVR) on marine macroalgae of this site. UVR conditions showed a strong seasonal variation, which was less pronounced toward longer wavelengths. Daily maximum dose rates (clear days) averaged in winter-summer: UV-B(290-315 nm) 0.30-2.1, UV-B(290-320 nm) 0.70-3.7, UV-A(315-400 nm) 20.6-62.1, UV-A(320-400 nm) 20.2-60.5 W m(-2), and photosynthetically active radiation (PAR) 969-2423 micromol m(-2) s(-1). The corresponding daily doses (all the days) ranged: UV-B(290-315 nm) 2.6-40.7, UV-B(290-320 nm) 6.7-78.5, UV-A(315-400 nm) 228-1539, UV-A(320-400 nm) 224-1501, and PAR 2008-13308 kJ m(-2) d(-1). Taking into consideration action spectra of a biological interest, the risk of UV exposure could be up to 37 times higher in summer than in winter. The photosynthetic activity (as maximum quantum yield of chlorophyll fluorescence, F(v)/F(m)) of the brown alga Lessonia nigrescens from the infralittoral zone was markedly more sensitive to UVR than of the green alga Enteromorpha intestinalis from the upper midlittoral, and the UV-B wave band increased markedly photoinhibition. In L. nigrescens, maximal photoinhibition (40%) took place at weighted (the action spectrum for photoinhibition of photosynthesis) UVR doses of 800 kJ m(-2), irrespective of the season (corresponding midsummer daily dose in Valdivia is 480 kJ m(-2)). In winter, when this alga was at its most sensitive, the weighted UV dose causing 35-40% photoinhibition was around 200 kJ m(-2). In E. intestinalis, weighted doses of 800 kJ m(-2) resulted in low photoinhibition (<10 %) and no clear seasonal patterns could be inferred. These results confirm that midday summer levels of UV-B and their daily doses in southern Chile are high enough to produce stress to intertidal macroalgae.     

Partial Colocalization of Oxidized,N-formylkynurenine-containing Proteins in Mitochondria and Golgi of Keratinocytes†

Proteins are the dominant cellular target for oxidative reactions because they comprise the majority of macromolecules. Posttranslational oxidative protein modifications include fragmentation, aggregation and alteration of specific amino acid residues. The amino acids and amino acid residues most susceptible to oxidative modification are those containing sulfur and those with aromatic rings. Tryptophan reacts with radicals, ozone and singlet oxygen to form the end product N-formylkynurenine (NFK). We recently described a novel anti-NFK antiserum and validated its use in immunological assays for the specific detection of NFK in isolated proteins and protein mixtures. Here we photo-oxidize rose bengal-containing HaCaT keratinocyte cells and examine the results using fluorescent confocal microscopy and staining with anti-NFK antiserum and markers for both Golgi and mitochondria. We show that photosensitization mediates the accumulation of NFK and that NFK can be detected in photosensitized cells with only slightly decreased viability. Additionally, we detect NFK-modified proteins in both Golgi and mitochondria of photosensitized cells. These experiments demonstrate that we have developed a tool for the specific detection of oxidized tryptophan residues in cells and suggest that this tool could be useful in tracking the fate of these oxidized proteins.     

Does Enhanced Solar UV‐B Radiation Affect Marine Primary Producers in Their Natural Habitats?

This article is a highlight of the paper by Li et al. in this issue of Photochemistry and Photobiology as well as a short summary of the research on the effects of solar UV-B radiation on primary production in the oceans. Laboratory experiments under controlled conditions using artificial light sources indicate species-specific damage of many phytoplankton groups. Mesocosm studies in enclosures of limited volume allow analyzing UV effects in multigeneration monitoring of natural assemblages. Field studies to determine the effects of short-wavelength solar radiation require sensitive instrumentation and measurements over extended areas of the open ocean to yield significant results. Results from a cruise described in the paper by Li et al. indicate clear effects of UV-B and UV-A on the photosynthetic carbon fixation of phytoplankton communities with spatial differences between coastal and open-ocean waters. Increasing temperatures and acidification in the ocean due to global climate change may exacerbate the detrimental effects of solar UV-B radiation.     

The States,Diffusion, and Concentration Distribution of Water in Radiation‐Formed PVA/PVP Hydrogels

Abstract

Hydrogels with various compositions of polyvinyl alcohol (PVA) and poly(1‐vinyl‐2‐ pyrrolidinone) (PVP) were prepared by irradiating mixtures of PVA and PVP in aqueous solutions with gamma‐rays from ⁶⁰Co sources at room temperature. The states of water in the hydrogels were characterized using DSC and NMR T₂ relaxation measurements and the kinetics of water diffusion in the hydrogels were studied by sorption experiments and NMR imaging. The DSC endothermic peaks in the temperature range ?10 to +10°C implied that there are at least two kinds of freezable water present in the matrix. The difference between the total water content and the freezable water content was referred to as bound water, which is not freezable. The weight fraction of water at which only nonfreezable water is present in a hydrogel with F_VP=0.19 has been estimated to be g_H2O/g_Polymer=0.375. From water sorption experiments, it was demonstrated that the early stage of the diffusion of water into the hydrogels was Fickian. A curve‐fit of the early‐stage experimental data to the Fickian model allowed determination of the water diffusion coefficient, which was found to lie between 1.5×10^?11 m² s^?1 and 4.5×10^?11 m² s^?1, depending on the polymer composition, the cross‐link density, and the temperature. It was also found that the energy barrier for diffusion of water molecules into PVA/PVP hydrogels was ≈24 kJ mol^?1. Additionally, the diffusion coefficients determined from NMR imaging of the volumetric swelling of the gels agreed well with the results obtained by the mass sorption method.     

Shining Light on Skin Pigmentation: The Darker and the Brighter Side of Effects of UV Radiation(†)

The term barrier function as applied to human skin often connotes the physical properties of this organ that provides protection from its surrounding environment. This term does not generally include skin pigmentation. However, skin pigmentation, which is the result of melanin produced in melanocytes residing in the basal layer of the skin and exported to the keratinocytes in the upper layers, serves equally important protective function. Indeed, changes in skin pigmentation are often the most readily recognized indicators of exposure of skin to damaging agents, especially to natural and artificial radiation in the environment. Several recent studies have shed new light on (1) the mechanisms involved in selective effects of subcomponents of UV radiation on human skin pigmentation and (2) the interactive influences between keratinocytes and melanocytes, acting as "epidermal melanin unit," that manifest as changes in skin pigmentation in response to exposure to various forms of radiation. This article provides a concise review of our current understanding of the effects of the nonionizing solar radiation, at cellular and molecular levels, on human skin pigmentation.     

Solar blind photocell – a simple element specific detector in Hg, As and Se speciation

An element-specific detection method, based on atomic absorption spectrometry (AAS) using solar blind photocells instead of a dispersion system, is described for the determination of Hg-, As-, and Se-species. Spectrometric investigations of AAS background lamps for As and Se measured with a CsI-cathode photocell shows its quality as narrow band detector. Species determination can be carried out subsequently to prior separation by HPLC or GC. The LODs for alkylated Hg species were below 1 ng/L, and for methylated As species below 1 μg/L. The relative standard deviation was < 10%. With the components described the production of cheap and automated dedicated speciation spectrometers is possible. Received: 18 May 1999 / Revised: 6 September 1999 / Accepted: 13 September 1999     

Purification and in vitro Activity of an Antimicrobial Peptide from Skin of Rana Temporaria Chensinensis, David

In this study,an antimicrobial component(RTCI)was purified from the skin of Rana temporaria chensinensis,David.Antimicrobial activities of RTCI against clinical multi-drug resistant bacterial strains,including Escherichia coli,Pseudomonas aeruginosa,Staphylococcus aureaus,Klebsiella oxytoca,Klebsiella pneumoniae,Enterococcus faecalis,and Proteus mirabilis were measured in vitro by means of minimal inhibitory concentration and time-kill studies.The results indicate that RTCI could inhibit the growth of these bacteria at a proper concentration and suggest that RTCI shows a better antimicrobial activity to Gram-negative bacterial strains than to Gram-positive bacterial strains.