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Ultraviolet C (UVC) light has long been used as a sterilizing agent, primarily through devices that emit at 254 nm. Depending on the dose and duration of exposure, UV 254 nm can cause erythema and photokeratitis and potentially cause skin cancer since it directly modifies nitrogenated nucleic acid bases. Filtered KrCl excimer lamps (emitting mainly at 222 nm) have emerged as safer germicidal tools and have even been proposed as devices to sterilize surgical wounds. All the studies that showed the safety of 222 nm analyzed cell number and viability, erythema generation, epidermal thickening, the formation of genetic lesions such as cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproducts (6-4PPs) and cancer-inducing potential. Although nucleic acids can absorb and be modified by both UV 254 nm and UV 222 nm equally, compared to UV 254 nm, UV 222 nm is more intensely absorbed by proteins (especially aromatic side chains), causing photooxidation and cross-linking. Here, in addition to analyzing DNA lesion formation, for the first time, we evaluated changes in the proteome and cellular pathways, reactive oxygen species formation, and metalloproteinase (MMP) levels and activity in full-thickness in vitro reconstructed human skin (RHS) exposed to UV 222 nm. We also performed the longest (40 days) in vivo study of UV 222 nm exposure in the HRS/J mouse model at the occupational threshold limit value (TLV) for indirect exposure (25 mJ/cm 2 ) and evaluated overall skin morphology, cellular pathological alterations, CPD and 6-4PP formation and MMP-9 activity. Our study showed that processes related to reactive oxygen species and inflammatory responses were more altered by UV 254 nm than by UV 222 nm. Our chronic in vivo exposure assay using the TLV confirmed that UV 222 nm causes minor damage to the skin. However, alterations in pathways related to skin regeneration raise concerns about direct exposure to UV 222 nm., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Renata Spagolla Napoleao Tavares reports financial support was provided by Vale SA. Douglas Adamoski reports financial support was provided by Vale SA. Alessandra Girasole reports financial support was provided by Vale SA. Rafael Elias Marques reports financial support was provided by Vale SA. Sandra Martha Gomes Dias reports financial support was provided by Vale SA., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ultraviolet (UV) light can inactivate SARS-CoV-2. However, the practicality of UV light is limited by the carcinogenic potential of mercury vapor-based UV lamps. Recent advances in the development of krypton chlorine (KrCl) excimer lamps hold promise, as these emit a shorter peak wavelength (222 nm), which is highly absorbed by the skin's stratum corneum and can filter out higher wavelengths. In this sense, UV 222 nm irradiation for the inactivation of virus particles in the air and surfaces is a potentially safer option as a germicidal technology. However, these same physical properties make it harder to reach microbes present in complex solutions, such as saliva, a critical source of SARS-CoV-2 transmission. We provide the first evaluation for using a commercial filtered KrCl excimer light source to inactivate SARS-CoV-2 in saliva spread on a surface. A conventional germicidal lamp (UV 254 nm) was also evaluated under the same condition. Using plaque-forming units (PFU) and Median Tissue Culture Infectious Dose (TCID 50 ) per milliliter we found that 99.99% viral clearance (LD 99.99 ) was obtained with 106.3 mJ/cm 2 of UV 222 nm for virus in DMEM and 2417 mJ/cm 2 for virus in saliva. Additionally, our results showed that the UV 254 nm had a greater capacity to inactivate the virus in both vehicles. Effective (after discounting light absorption) LD 99.99 of UV 222 nm on the virus in saliva was ∼30 times higher than the value obtained with virus in saline solution (PBS), we speculated that saliva might be protecting the virus from surface irradiation in ways other than just by intensity attenuation of UV 222 nm. Due to differences between UV 222/254 nm capacities to interact and be absorbed by molecules in complex solutions, a higher dose of 222 nm will be necessary to reduce viral load in surfaces with contaminated saliva., (Copyright © 2022. Published by Elsevier B.V.)

Leishmaniasis is a group of diseases that have limited and high toxic therapeutic options. Herein, we evaluated the antileishmanial potential and cytotoxicity of hexanic extract obtained from the Antarctic brown alga Ascoseira mirabilis using bioguided fractionation against Leishmania amazonensis and murine macrophages, which was fractionated by SPE, yielding seven fractions (F1-F7). The fraction F6 showed good anti-amastigote activity (IC 50  = 73.4 ± 0.4 μg mL -1 ) and low cytotoxicity (CC 50  > 100 μg mL -1 ). Thus, in order to identify the bioactive constituent(s) of F6, the fraction was separated in a semipreparative HPLC, yielding four fractions (F6.1-F6.4). F6.2 was the most bioactive fraction (IC 50  = 66.5 ± 4.5 μg mL -1 ) and GC-MS analyses revealed that the compounds octadecane, propanoic acid, 1-monomyristin and azelaic acid correspond to 61% of its composition. These data show for the first time the antileishmanial potential of the Antarctic alga A. mirabilis .

Cancer is considered one of the most predominant diseases in the world and one of the principal causes of mortality per year. The cellular and molecular mechanisms involved in the development and establishment of solid tumors can be defined as tumorigenesis. Recent technological advances in the 3D cell culture field have enabled the recapitulation of tumorigenesis in vitro , including the complexity of stromal microenvironment. The establishment of these 3D solid tumor models has a crucial role in personalized medicine and drug discovery. Recently, spheroids and organoids are being largely explored as 3D solid tumor models for recreating tumorigenesis in vitro . In spheroids, the solid tumor can be recreated from cancer cells, cancer stem cells, stromal and immune cell lineages. Organoids must be derived from tumor biopsies, including cancer and cancer stem cells. Both models are considered as a suitable model for drug assessment and high-throughput screening. The main advantages of 3D bioprinting are its ability to engineer complex and controllable 3D tissue models in a higher resolution. Although 3D bioprinting represents a promising technology, main challenges need to be addressed to improve the results in cancer research. The aim of this review is to explore (1) the principal cell components and extracellular matrix composition of solid tumor microenvironment; (2) the recapitulation of tumorigenesis in vitro using spheroids and organoids as 3D culture models; and (3) the opportunities, challenges, and applications of 3D bioprinting in this area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kronemberger, Miranda, Tavares, Montenegro, Kopke and Baptista.)

Marine-derived fungi proved to be a rich source of biologically active compounds. The genus Penicillium has been extensively studied regarding their secondary metabolites and biological applications. However, the photoprotective effects of these metabolites remain underexplored. Herein, the photoprotective potential of Penicillium echinulatum, an Antarctic alga-associated fungus, was assessed by UV absorption, photostability study, and protection from UVA-induced ROS generation assay on human immortalized keratinocytes (HaCaT) and reconstructed human skin (RHS). The photosafety was evaluated by the photoreactivity (OECD TG 495) and phototoxicity assays, performed by 3T3 neutral red uptake (3T3 NRU PT, OECD TG 432) and by the RHS model. Through a bio-guided purification approach, four known alkaloids, (-)-cyclopenin (1), dehydrocyclopeptine (2), viridicatin (3), and viridicatol (4), were isolated. Compounds 3 and 4 presented absorption in UVB and UVA-II regions and were considered photostable after UVA irradiation. Despite compounds 3 and 4 showed phototoxic potential in 3T3 NRU PT, no phototoxicity was observed in the RHS model (reduction of cell viability < 30%), which indicates their very low acute photoirritation and high photosafety potential in humans. Viridicatin was considered weakly photoreactive, while viridicatol showed no photoreactivity; both compounds inhibited UVA-induced ROS generation in HaCaT cells, although viridicatol was not able to protect the RHS model against UVA-induced ROS production. Thus, the results highlighted the photoprotective and antioxidant potential of metabolites produced by P. echinulatum which can be considered a new class of molecules for photoprotection, since their photosafety and non-cytotoxicity were predicted using recommended in vitro methods for topical use., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Skin model cultivation under static conditions limits the observation of the toxicity to this single organ. Biology-inspired microphysiological systems associating skin with a liver in the same circulating medium provide a more comprehensive insight into systemic substance toxicity; however, its advantages or limitations for topical substance toxicity remain unknown. Herein, we performed topical (OECD test guideline no. 439) and systemic administration of terbinafine in reconstructed human skin (RHS) vs. a RHS plus liver model cultured in TissUse' HUMIMIC Chip2 (Chip2). Aiming for a more detailed insight into the cutaneous substance irritancy/toxicity, we assessed more than the MTT cell viability: lactate dehydrogenase (LDH), lactate and glucose levels, as well as inherent gene expressions. Sodium dodecyl sulfate (SDS) was the topical irritant positive control. We confirmed SDS irritancy in both static RHS and Chip2 culture by the damage in the morphology, reduction in the lactate production and lower glucose consumption. In the static RHS, the SDS-treated tissues also released significantly high LDH (82%; p < 0.05) and significantly lower IL-6 release (p < 0.05), corroborating with the other metabolic levels. In both static RHS and Chip2 conditions, we confirmed absence of irritancy or systemic toxicity by LDH, glucose or lactate levels for topical 1% and 5% terbinafine and systemic 0.1% terbinafine treatment. However, topical 5% terbinafine treatment in the Chip2 upregulated IL-1α in the RHS, unbalanced apoptotic and proliferative cell ratios in the liver and significantly increased its expression of CYP1A2 and 3A4 enzymes (p < 0.05), proving that it has passed the RHS barrier promoting a liver impact. Systemic 0.1% terbinafine treatment in the Chip2 increased RHS expression of EGFR, increased apoptotic cells in the liver, downregulated liver albumin expression and upregulated CYP2C9 significantly (p < 0.05), acting as an effective hepatotoxic terbinafine control. The combination of the RHS and liver model in the Chip2 allowed a more sensitive assessment of skin and hepatic effects caused by chemicals able to pass the skin (5% terbinafine and SDS) and after systemic 0.1% terbinafine application. The present study opens up a more complex approach based on the microphysiological system to assess more than a skin irritation process., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Fucoxanthin possesses a well-described antioxidant activity that might be useful for human skin photoprotection. However, there is a lack of scientific information regarding its properties when applied onto human skin. Thus, the objective of the present study was to assess the photoprotective and phototoxicity potential of fucoxanthin based on its ultraviolet (UVB 280-320 nm; UVA 320-400 nm) and visible (VIS 400-700 nm) absorption, photostability, phototoxicity in 3T3 mouse fibroblast culture vs. full-thickness reconstructed human skin (RHS), and its ability to inhibit reactive oxygen species formation that is induced by UVA on HaCaT keratinocytes. Later, we evaluated the antioxidant properties of the sunscreen formulation plus 0.5% fucoxanthin onto RHS to confirm its bioavailability and antioxidant potential through the skin layers. The compound was isolated from the alga Desmarestia anceps . Fucoxanthin, despite presenting chemical photo-instability (dose 6 J/cm 2 : 35% UVA and 21% VIS absorbance reduction), showed acceptable photodegradation (dose 27.5 J/cm 2 : 5.8% UVB and 12.5% UVA absorbance reduction) when it was added to a sunscreen at 0.5% ( w / v ). In addition, it increased by 72% of the total sunscreen UV absorption spectra, presenting UV-booster properties. Fucoxanthin presented phototoxic potential in 3T3 fibroblasts (mean photo effect 0.917), but it was non-phototoxic in the RHS model due to barrier function that was provided by the stratum corneum. In addition, it showed a significant inhibition of ROS formation at 0.01% ( p < 0.001), in HaCat, and in a sunscreen at 0.5% ( w / v ) ( p < 0.001), in RHS. In conclusion, in vitro results showed fucoxanthin protective potential to the skin that might contribute to improving the photoprotective potential of sunscreens in vivo.

Considering the global trend in the search for alternative natural compounds with antioxidant and sun protection factor (SPF) boosting properties, bacterial carotenoids represent an opportunity for exploring pigments of natural origin which possess high antioxidant activity, lower toxicity, no residues, and no environmental risk and are readily decomposable. In this work, three pigmented bacteria from the Antarctic continent, named Arthrobacter agilis 50cyt, Zobellia laminarie 465, and Arthrobacter psychrochitiniphilus 366, were able to withstand UV-B and UV-C radiation. The pigments were extracted and tested for UV absorption, antioxidant capacity, photostability, and phototoxicity profile in murine fibroblasts (3T3 NRU PT-OECD TG 432) to evaluate their further potential use as UV filters. Furthermore, the pigments were identified by ultra-high-performance liquid chromatography-photodiode array detector-mass spectrometry (UPLC-PDA-MS/MS). The results showed that all pigments presented a very high antioxidant activity and good stability under exposure to UV light. However, except for a fraction of the A. agilis 50cyt pigment, they were shown to be phototoxic. A total of 18 different carotenoids were identified from 23 that were separated on a C18 column. The C50 carotenes bacterioruberin and decaprenoxanthin (including its variations) were confirmed for A. agilis 50cyt and A. psychrochitiniphilus 366, respectively. All-trans-bacterioruberin was identified as the pigment that did not express phototoxic activity in the 3T3 NRU PT assay (MPE < 0.1). Zeaxanthin, β-cryptoxanthin, β-carotene, and phytoene were detected in Z. laminarie 465. In conclusion, carotenoids identified in this work from Antarctic bacteria open perspectives for their further biotechnological application towards a more sustainable and environmentally friendly way of pigment exploitation.

An iridescent yellow pigmented bacterium isolated from the Antarctic continent, named Cellulophaga fucicola strain 416, was found to be able to tolerate UV-B radiation. Its crude pigment extract was tested for antioxidant capacity, UV light stability and phototoxicity profile against murine fibroblast lines. The pigments were further isolated and chemically identified by ultra-high-performance liquid chromatography with photodiode array and mass spectrometry detectors. The results showed that the pigment extract presented weak stability under exposure to UV light, a phototoxic profile in the 3t3 Neutral Red Uptake test and a very high antioxidant activity, suggesting that it could be used as food and feed colourants. Zeaxanthin and two isomers of zeaxanthin, β-cryptoxanthin and β-carotene, were identified using a C18 column. These five carotenoids were the major pigments isolated from C. fucicola 416. In conclusion, the identification of pigments produced by the bacterial strain under study may help us understand how bacteria thrive in high UV and cold environments, and opens avenues for further biotechnological application towards a more sustainable and environmentally friendly way of pigment exploitation.

Natural products, or secondary metabolites, obtained from fungal species associated with marine algae have been widely used in sunscreens due to their antioxidant activity and protective potential against solar radiation. The endophytic fungus isolated from Bostrychia radicans algae collected in the Rio Escuro mangrove, São Paulo State, Brazil, Annulohypoxylon stygium (Xylariaceae family) was studied to evaluate the photoprotective potential of its metabolites. The Annulohypoxylon genus can produce secondary metabolites with interesting cytotoxic, antibacterial and antioxidant properties and was never isolated before from a marine alga or had its metabolites studied for UV protection. The fungal culture (code As) extracted with dichloromethane: methanol (2:1) yielded 9 fractions (Asa to Asi) which were submitted to different chromatographic methodologies to obtain pure compounds, and to spectroscopic methodologies to elucidate their structures. Also, a screening was conducted to evaluate the qualitative production of the metabolites, besides the absorption in the UVA/UVB range, their photostability and phototoxicity potential using the 3T3 NRU phototoxicity test (OECD TG 432). This study led to the isolation of a novel compound, 3-benzylidene-2-methylhexahydropyrrolo [1,2-α] pyrazine-1,4-dione (1), from fractions Ase3 and Asf3; Ase1 was identified as 1-(1,3-Benzodioxol-5-yl)-1,2-propanediol (2), two metabolites were isolated as diastereomers (1S,2R)-1-phenyl-1,2-propanediol (3) from Asd2 and (1R,2R)-1-phenyl-1,2-propanediol (4) from Asd3, and Ase1 and 1,3-benzodioxole-5-methanol (5) from Asc1. The results obtained showed a great potential source of new molecules to be used as UVB filters in sunscreens, since substances 1-2 presented UVB absorption, had no phototoxic potential and were considered photostable. In conclusion, these compounds can be considered as a potential new class of molecules for photoprotection, since their photosafety and non-cytotoxicity were predicted using in vitro methods for topical use. Meanwhile, further efficacy assays shall be conducted for the establishment of their Sun Protection Factor (SPF). Also, this work provided new information concerning the metabolic profile of A. stygium, since it was possible to obtain two enantiomer compounds (3) and (4). One of them belonged to the same skeleton, but with a methylenedioxy moiety, showing the richest enzymatic pattern for this microorganism., (Copyright © 2017 Elsevier B.V. All rights reserved.)