Pub Date : 2024-09-01Epub Date: 2024-02-05DOI: 10.1111/php.13917
Sami S Qutob, Samantha P M Roesch, Sandy Smiley, Pascale Bellier, Andrew Williams, Kate B Cook, Matthew J Meier, Andrea Rowan-Carroll, Carole L Yauk, James P McNamee
Exposure to ultraviolet radiation (UV-R), from both natural and artificial tanning, heightens the risk of skin cancer by inducing molecular changes in cells and tissues. Despite established transcriptional alterations at a molecular level due to UV-R exposure, uncertainties persist regarding UV radiation characterization and subsequent genomic changes. Our study aimed to mechanistically explore dose- and time-dependent gene expression changes, that may drive short-term (e.g., sunburn) and long-term actinic (e.g., skin cancer) consequences. Using C57BL/6N mouse skin, we analyzed transcriptomic expression following exposure to five erythemally weighted UV-R doses (0, 5, 10, 20, and 40 mJ/cm2) emitted by a UV-R tanning device. At 96 h post-exposure, 5 mJ/cm2 induced 116 statistically significant differentially expressed genes (DEGs) associated with structural changes from UV-R damage. The highest number of significant gene expression changes occurred at 6 and 48 h post-exposure in the 20 and 40 mJ/cm2 dose groups. Notably, at 40 mJ/cm2, 13 DEGs related to skin barrier homeostasis were consistently perturbed across all timepoints. UV-R exposure activated pathways involving oxidative stress, P53 signaling, inflammation, biotransformation, skin barrier maintenance, and innate immunity. This in vivo study's transcriptional data offers mechanistic insights into both short-term and potential non-threshold-dependent long-term health effects of UV-R tanning.
{"title":"Transcriptome analysis in mouse skin after exposure to ultraviolet radiation from a canopy sunbed.","authors":"Sami S Qutob, Samantha P M Roesch, Sandy Smiley, Pascale Bellier, Andrew Williams, Kate B Cook, Matthew J Meier, Andrea Rowan-Carroll, Carole L Yauk, James P McNamee","doi":"10.1111/php.13917","DOIUrl":"10.1111/php.13917","url":null,"abstract":"<p><p>Exposure to ultraviolet radiation (UV-R), from both natural and artificial tanning, heightens the risk of skin cancer by inducing molecular changes in cells and tissues. Despite established transcriptional alterations at a molecular level due to UV-R exposure, uncertainties persist regarding UV radiation characterization and subsequent genomic changes. Our study aimed to mechanistically explore dose- and time-dependent gene expression changes, that may drive short-term (e.g., sunburn) and long-term actinic (e.g., skin cancer) consequences. Using C57BL/6N mouse skin, we analyzed transcriptomic expression following exposure to five erythemally weighted UV-R doses (0, 5, 10, 20, and 40 mJ/cm<sup>2</sup>) emitted by a UV-R tanning device. At 96 h post-exposure, 5 mJ/cm<sup>2</sup> induced 116 statistically significant differentially expressed genes (DEGs) associated with structural changes from UV-R damage. The highest number of significant gene expression changes occurred at 6 and 48 h post-exposure in the 20 and 40 mJ/cm<sup>2</sup> dose groups. Notably, at 40 mJ/cm<sup>2</sup>, 13 DEGs related to skin barrier homeostasis were consistently perturbed across all timepoints. UV-R exposure activated pathways involving oxidative stress, P53 signaling, inflammation, biotransformation, skin barrier maintenance, and innate immunity. This in vivo study's transcriptional data offers mechanistic insights into both short-term and potential non-threshold-dependent long-term health effects of UV-R tanning.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-02-13DOI: 10.1111/php.13921
Thierry Douki, Daniel Bacqueville, Carine Jacques, Camille Geniès, Nicolas Roullet, Sandrine Bessou-Touya, Hélène Duplan
In recent years, interest is growing in the biological cutaneous effects of high-energy visible light (400-450 nm). In the present study, we explored the impact of blue light (BL) on the repair of pyrimidine dimers, the major class of premutagenic DNA damage induced by exposure to sunlight. We unambiguously demonstrate that the exposure of in vitro reconstructed human epidermis to environmentally relevant doses of BL strongly decreases the rate of repair of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts induced by a subsequent UVB irradiation. Using the highly sensitive and specific liquid chromatography-tandem mass spectrometry assay, we did not observe induction of pyrimidine dimers by BL alone. Finally, we showed that application, during the BL exposure step, of a formula containing a new filter, named TriAsorB and affording BL photoprotection, prevented the decrease in DNA repair efficiency. These results emphasize the potential deleterious effects of BL on DNA repair and the interest in providing adequate skin protection against this wavelength range of sunlight.
近年来,人们对高能可见光(400-450 nm)的皮肤生物效应越来越感兴趣。在本研究中,我们探讨了蓝光(BL)对嘧啶二聚体修复的影响,嘧啶二聚体是日光照射诱发的主要一类致突变前 DNA 损伤。我们明确地证明,将体外重建的人体表皮暴露于环境相关剂量的蓝光中,会大大降低环丁烷嘧啶二聚体和嘧啶(6-4)嘧啶酮光产物的修复率,而这些光产物是由随后的紫外线照射诱发的。利用高灵敏度和高特异性的液相色谱-串联质谱分析法,我们没有观察到 BL 单独诱导的嘧啶二聚体。最后,我们发现,在紫外线照射步骤中使用一种含有新型滤光器(名为 TriAsorB,具有紫外线光保护作用)的配方,可以防止 DNA 修复效率的降低。这些结果强调了碱性蓝光对 DNA 修复的潜在有害影响,以及针对这一波长范围的阳光提供充分的皮肤保护的重要性。
{"title":"Blue light impairs the repair of UVB-induced pyrimidine dimers in a human skin model.","authors":"Thierry Douki, Daniel Bacqueville, Carine Jacques, Camille Geniès, Nicolas Roullet, Sandrine Bessou-Touya, Hélène Duplan","doi":"10.1111/php.13921","DOIUrl":"10.1111/php.13921","url":null,"abstract":"<p><p>In recent years, interest is growing in the biological cutaneous effects of high-energy visible light (400-450 nm). In the present study, we explored the impact of blue light (BL) on the repair of pyrimidine dimers, the major class of premutagenic DNA damage induced by exposure to sunlight. We unambiguously demonstrate that the exposure of in vitro reconstructed human epidermis to environmentally relevant doses of BL strongly decreases the rate of repair of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts induced by a subsequent UVB irradiation. Using the highly sensitive and specific liquid chromatography-tandem mass spectrometry assay, we did not observe induction of pyrimidine dimers by BL alone. Finally, we showed that application, during the BL exposure step, of a formula containing a new filter, named TriAsorB and affording BL photoprotection, prevented the decrease in DNA repair efficiency. These results emphasize the potential deleterious effects of BL on DNA repair and the interest in providing adequate skin protection against this wavelength range of sunlight.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amin Yao, Yu Zhang, Mengting Ouyang, Lei Wen, Wei Lai
Transfer RNA-derived small RNAs (tsRNAs) refer to a newly established family of non-coding RNAs that regulate a diverse set of biological processes. However, the function of tsRNAs in skin photoaging remains unclear. This research aims to investigate the potential correlation between tsRNAs and skin photoaging. Human dermal fibroblasts (HDFs) were irradiated with UVA at 10 J/cm2 once a day lasting for 14 days, resulting in the establishment of a photoaging model induced by UVA. To identify the expression profiles and functions of tsRNAs, tsRNA sequencing and bioinformatics analysis were conducted. qPCR was employed to validate the results of differentially expressed (DE) tsRNAs. A total of 34 tsRNAs exhibited significant differential expression between the UVA and control groups (n = 3), with nine upregulated and 25 downregulated (log2 fold change >1.5, p-value <0.05). Six tsRNAs were selected at random and validated by qRT-PCR. The enrichment analysis of DE tsRNAs target genes indicated that the dysregulated tsRNAs appeared to be connected with cell cycle, DNA replication and the AGE-RAGE signaling pathway. The expression of tsRNAs was found to be aberrant in UVA-HDF. These findings provide insights into the UVA-induced damage and potential target genes for skin photoaging.
{"title":"Expression profiles and functional analysis of transfer RNA-derived small RNAs (tsRNAs) in photoaged human dermal fibroblasts.","authors":"Amin Yao, Yu Zhang, Mengting Ouyang, Lei Wen, Wei Lai","doi":"10.1111/php.14015","DOIUrl":"https://doi.org/10.1111/php.14015","url":null,"abstract":"<p><p>Transfer RNA-derived small RNAs (tsRNAs) refer to a newly established family of non-coding RNAs that regulate a diverse set of biological processes. However, the function of tsRNAs in skin photoaging remains unclear. This research aims to investigate the potential correlation between tsRNAs and skin photoaging. Human dermal fibroblasts (HDFs) were irradiated with UVA at 10 J/cm<sup>2</sup> once a day lasting for 14 days, resulting in the establishment of a photoaging model induced by UVA. To identify the expression profiles and functions of tsRNAs, tsRNA sequencing and bioinformatics analysis were conducted. qPCR was employed to validate the results of differentially expressed (DE) tsRNAs. A total of 34 tsRNAs exhibited significant differential expression between the UVA and control groups (n = 3), with nine upregulated and 25 downregulated (log<sub>2</sub> fold change >1.5, p-value <0.05). Six tsRNAs were selected at random and validated by qRT-PCR. The enrichment analysis of DE tsRNAs target genes indicated that the dysregulated tsRNAs appeared to be connected with cell cycle, DNA replication and the AGE-RAGE signaling pathway. The expression of tsRNAs was found to be aberrant in UVA-HDF. These findings provide insights into the UVA-induced damage and potential target genes for skin photoaging.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keyvan Khosh Abady, Negar Karpourazar, Arjun Krishnamoorthi, Runze Li, Peter M Rentzepis
With the rise of bacterial infections and antibiotic resistance, spectroscopic devices originally developed for bacterial detection have shown promise to rapidly identify bacterial strains and determine the ratio of live to dead bacteria. However, the detection of the photoreactivated pathogens remains a critical concern. This study utilizes fluorescence and Raman spectroscopy to analyze bacterial responses to UV irradiation and subsequent photoreactivation. Our experimental results reveal limitations in fluorescence spectroscopy for detecting photoreactivated bacteria, as the intense fluorescence of tryptophan and tyrosine amino acids masks the fluorescence emitted by thymine molecules. Conversely, Raman spectroscopy proves more effective, showing a detectable decrease in band intensities of E. coli bacteria at 1248 and 1665 cm-1 after exposure to UVC radiation. Subsequent UVA irradiation results in the partial restoration of these band intensities, indicating DNA repair and bacterial photoreactivation. This enhanced understanding aims to improve the accuracy and effectiveness of these spectroscopic tools in clinical and environmental settings.
随着细菌感染和抗生素耐药性的增加,最初为细菌检测而开发的光谱设备在快速识别细菌菌株和确定活菌与死菌的比例方面大有可为。然而,对光活化病原体的检测仍然是一个关键问题。本研究利用荧光和拉曼光谱分析细菌对紫外线照射和随后的光氧化活化的反应。我们的实验结果揭示了荧光光谱在检测光活化细菌方面的局限性,因为色氨酸和酪氨酸氨基酸的强烈荧光会掩盖胸腺嘧啶分子发出的荧光。相反,拉曼光谱则更为有效,它显示大肠杆菌在受到紫外线辐射后,1248 和 1665 cm-1 处的带强度会出现可检测到的下降。随后的 UVA 照射导致这些波段强度部分恢复,表明 DNA 修复和细菌光复活。加深对这一现象的了解有助于提高这些光谱工具在临床和环境中的准确性和有效性。
{"title":"Spectroscopic analysis of bacterial photoreactivation.","authors":"Keyvan Khosh Abady, Negar Karpourazar, Arjun Krishnamoorthi, Runze Li, Peter M Rentzepis","doi":"10.1111/php.14019","DOIUrl":"https://doi.org/10.1111/php.14019","url":null,"abstract":"<p><p>With the rise of bacterial infections and antibiotic resistance, spectroscopic devices originally developed for bacterial detection have shown promise to rapidly identify bacterial strains and determine the ratio of live to dead bacteria. However, the detection of the photoreactivated pathogens remains a critical concern. This study utilizes fluorescence and Raman spectroscopy to analyze bacterial responses to UV irradiation and subsequent photoreactivation. Our experimental results reveal limitations in fluorescence spectroscopy for detecting photoreactivated bacteria, as the intense fluorescence of tryptophan and tyrosine amino acids masks the fluorescence emitted by thymine molecules. Conversely, Raman spectroscopy proves more effective, showing a detectable decrease in band intensities of E. coli bacteria at 1248 and 1665 cm<sup>-1</sup> after exposure to UVC radiation. Subsequent UVA irradiation results in the partial restoration of these band intensities, indicating DNA repair and bacterial photoreactivation. This enhanced understanding aims to improve the accuracy and effectiveness of these spectroscopic tools in clinical and environmental settings.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ultraviolet radiation is a non-ionizing radiation produced by longer wavelength energy sources with lower frequency and is categorized into UV-A, UV-B, and UV-C. Minimal exposure to this radiation has several health benefits, which include treating microbial contaminations and skin therapies. However, the antimicrobial action of low-dose UV-A during pathogenic bacterial infections is still unrevealed. In this study, the impact of low-dose UV-A as pre- or post-treatment using the model organism, Caenorhabditis elegans with candidate pathogens (Acinetobacter baumannii and Staphylococcus aureus) mediated infections was investigated. The results indicated enrichment of metabolites, reduced level of antioxidants, increased expression of dopamine biosynthesis and transportation, and decrease in serotonin biosynthesis when the organism was exposed to low-dose UV-A for 5 min. This, in turn, elevated the expression of candidate regulatory proteins involved in lifespan determination, innate immunity, and cAMP-response element binding protein (CREB), which appear to increase the lifespan and brood size of C. elegans during A. baumannii and S. aureus infections. The findings suggested that the low-dose UV-A treatment during A. baumannii and S. aureus infections prolonged the lifespan and increased the egg-laying capacity of C. elegans.
紫外线辐射是一种非电离辐射,由波长较长、频率较低的能量源产生,分为紫外线 A、紫外线 B 和紫外线 C。微量暴露于这种辐射对健康有多种益处,包括治疗微生物污染和皮肤疗法。然而,低剂量 UV-A 在病原菌感染期间的抗菌作用仍未被揭示。在这项研究中,研究人员利用模型生物秀丽隐杆线虫与候选病原体(鲍曼不动杆菌和金黄色葡萄球菌)介导的感染,调查了低剂量紫外线-A 作为治疗前或治疗后的影响。结果表明,当生物体暴露于低剂量紫外线 A 5 分钟时,代谢物丰富,抗氧化剂水平降低,多巴胺生物合成和运输表达增加,血清素生物合成减少。这反过来又提高了涉及寿命决定、先天免疫和 cAMP 反应元件结合蛋白(CREB)的候选调控蛋白的表达,而这些蛋白似乎能在鲍曼不动杆菌和金黄色葡萄球菌感染期间增加秀丽隐杆线虫的寿命和育雏规模。研究结果表明,在鲍曼不动杆菌和金黄色葡萄球菌感染期间进行低剂量紫外线-A处理可延长秀丽隐杆线虫的寿命并提高其产卵能力。
{"title":"Impact of low-dose UV-A in Caenorhabditis elegans during candidate bacterial infections.","authors":"Balasubramanian Chellammal Muthubharathi, Pandiarajan Kaarmegam Subalakshmi, Bynedi Sheshatri Chinna Mounish, Toleti Subba Rao, Krishnaswamy Balamurugan","doi":"10.1111/php.14009","DOIUrl":"https://doi.org/10.1111/php.14009","url":null,"abstract":"<p><p>Ultraviolet radiation is a non-ionizing radiation produced by longer wavelength energy sources with lower frequency and is categorized into UV-A, UV-B, and UV-C. Minimal exposure to this radiation has several health benefits, which include treating microbial contaminations and skin therapies. However, the antimicrobial action of low-dose UV-A during pathogenic bacterial infections is still unrevealed. In this study, the impact of low-dose UV-A as pre- or post-treatment using the model organism, Caenorhabditis elegans with candidate pathogens (Acinetobacter baumannii and Staphylococcus aureus) mediated infections was investigated. The results indicated enrichment of metabolites, reduced level of antioxidants, increased expression of dopamine biosynthesis and transportation, and decrease in serotonin biosynthesis when the organism was exposed to low-dose UV-A for 5 min. This, in turn, elevated the expression of candidate regulatory proteins involved in lifespan determination, innate immunity, and cAMP-response element binding protein (CREB), which appear to increase the lifespan and brood size of C. elegans during A. baumannii and S. aureus infections. The findings suggested that the low-dose UV-A treatment during A. baumannii and S. aureus infections prolonged the lifespan and increased the egg-laying capacity of C. elegans.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the realm of Photodynamic Therapy, as elsewhere, claims are sometimes made for which there is minimal evidence or proof. Some examples are indicated.
在光动力疗法领域,与其他领域一样,有时也会出现证据或证明极少的说法。下面列举一些例子。
{"title":"Trials and errors in the realm of photodynamic therapy: Viability and ROS detection.","authors":"David Kessel","doi":"10.1111/php.14020","DOIUrl":"https://doi.org/10.1111/php.14020","url":null,"abstract":"<p><p>In the realm of Photodynamic Therapy, as elsewhere, claims are sometimes made for which there is minimal evidence or proof. Some examples are indicated.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yannick Port-Lougarre, Guillaume Voegeli, Bertrand Vileno, Elena Giménez-Arnau
Photoallergic contact dermatitis is a skin disease caused by combined exposure to photoreactive chemicals and sunlight. Exposure to allergens and the risk of skin sensitization is an essential regulatory issue within the industry. Yet, only few non-validated assays for photoallergy assessment exist as the pathogenesis is not fully deciphered. Improving such assays and/or developing new ones require an understanding of the chemical mechanisms involved. The first key event in the photosensitization process, namely chemical binding of the photoallergen to endogenous proteins, is thought to proceed via photo-mediated radicals arising from the photoallergen. Moreover, the mechanism of action of these radicals if formed in the epidermis is not known and far from being unraveled. We present here an original proof-of-concept methodology to probe radical generation from allergens in contact with photoexposed skin, using electron paramagnetic resonance and spin trapping in a reconstructed human epidermis model mimicking real-life exposure scenarios.
{"title":"Probing skin photoallergens in reconstructed human epidermis: An EPR spin trapping investigation.","authors":"Yannick Port-Lougarre, Guillaume Voegeli, Bertrand Vileno, Elena Giménez-Arnau","doi":"10.1111/php.14010","DOIUrl":"https://doi.org/10.1111/php.14010","url":null,"abstract":"<p><p>Photoallergic contact dermatitis is a skin disease caused by combined exposure to photoreactive chemicals and sunlight. Exposure to allergens and the risk of skin sensitization is an essential regulatory issue within the industry. Yet, only few non-validated assays for photoallergy assessment exist as the pathogenesis is not fully deciphered. Improving such assays and/or developing new ones require an understanding of the chemical mechanisms involved. The first key event in the photosensitization process, namely chemical binding of the photoallergen to endogenous proteins, is thought to proceed via photo-mediated radicals arising from the photoallergen. Moreover, the mechanism of action of these radicals if formed in the epidermis is not known and far from being unraveled. We present here an original proof-of-concept methodology to probe radical generation from allergens in contact with photoexposed skin, using electron paramagnetic resonance and spin trapping in a reconstructed human epidermis model mimicking real-life exposure scenarios.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luana B Trentin, Altevir R Viana, Sophia Iwersen, Bernardo A Iglesias, Otávio A Chaves, André P Schuch
Photodynamic therapy (PDT) combines a light source, oxygen, and a photosensitizer (PS) to generate reactive oxygen species (ROS) for treating diseases. In this study, we evaluated two meso-tetra-pyridyl porphyrins with [Pd(bpy)Cl]+, namely 3-PdTPyP and 4-PdTPyP, as PS for PDT application. DNA interaction was assessed by spectroscopic measurements (UV-Vis and fluorescence emission), viscosity analysis, and molecular docking simulations. The results indicate that Pd(II)-porphyrins do not intercalate into DNA, suggesting that the minor groove is the primary interaction site, mainly through van der Waals forces. These metalloporphyrins effectively induced nitrogenous bases oxidation, particularly in purines, after white light irradiation. The induced DNA lesions were able to inactivate plasmid DNA metabolism (DNA replication and transcription) in a bacterial model. 3-PdTPyP and 4-PdTPyP significantly decreased the viability of treated melanoma cell lines (A375 and B16-F10), demonstrating that melanoma cell lines were more sensitive to these Pd(II)-porphyrins than the fibroblast cell line (L929). Moreover, 3-PdTPyP was more photototoxic to A375 cells (IC50 = 0.43 μM), whereas 4-PdTPyP was more photototoxic to B16-F10 cells (IC50 = 0.51 μM). These findings suggest that these porphyrins are promising PS for future PDT research focused on skin cancer.
{"title":"Light exposure of tetra-cationic porphyrins containing peripheral Pd(II)-bipyridyl complexes and the induced effects on purified DNA molecule, fibroblast and melanoma cell lines.","authors":"Luana B Trentin, Altevir R Viana, Sophia Iwersen, Bernardo A Iglesias, Otávio A Chaves, André P Schuch","doi":"10.1111/php.14017","DOIUrl":"https://doi.org/10.1111/php.14017","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) combines a light source, oxygen, and a photosensitizer (PS) to generate reactive oxygen species (ROS) for treating diseases. In this study, we evaluated two meso-tetra-pyridyl porphyrins with [Pd(bpy)Cl]<sup>+</sup>, namely 3-PdTPyP and 4-PdTPyP, as PS for PDT application. DNA interaction was assessed by spectroscopic measurements (UV-Vis and fluorescence emission), viscosity analysis, and molecular docking simulations. The results indicate that Pd(II)-porphyrins do not intercalate into DNA, suggesting that the minor groove is the primary interaction site, mainly through van der Waals forces. These metalloporphyrins effectively induced nitrogenous bases oxidation, particularly in purines, after white light irradiation. The induced DNA lesions were able to inactivate plasmid DNA metabolism (DNA replication and transcription) in a bacterial model. 3-PdTPyP and 4-PdTPyP significantly decreased the viability of treated melanoma cell lines (A375 and B16-F10), demonstrating that melanoma cell lines were more sensitive to these Pd(II)-porphyrins than the fibroblast cell line (L929). Moreover, 3-PdTPyP was more photototoxic to A375 cells (IC50 = 0.43 μM), whereas 4-PdTPyP was more photototoxic to B16-F10 cells (IC50 = 0.51 μM). These findings suggest that these porphyrins are promising PS for future PDT research focused on skin cancer.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mustafa Kemal Ruhi, Brittany P Rickard, Marta Overchuk, Prima Dewi Sinawang, Elizabeth Stanley, Matthew Mansi, Raymond G Sierra, Brandon Hayes, Xianming Tan, Demir Akin, Bin Chen, Utkan Demirci, Imran Rizvi
Over 75% percent of ovarian cancer patients are diagnosed with advanced-stage disease characterized by unresectable intraperitoneal dissemination and the presence of ascites, or excessive fluid build-up within the abdomen. Conventional treatments include cytoreductive surgery followed by multi-line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced-stage ovarian cancer will relapse and succumb to platinum-resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial-to-mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS-induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro-drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence-based biomarker of FSS-induced platinum resistance. Additionally, this study investigates the efficacy of PpIX-enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov-3 and NIH:OVCAR-3 cells, two representative cell lines for high-grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA-PpIX-mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX-mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence-based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.
{"title":"PpIX-enabled fluorescence-based detection and photodynamic priming of platinum-resistant ovarian cancer cells under fluid shear stress.","authors":"Mustafa Kemal Ruhi, Brittany P Rickard, Marta Overchuk, Prima Dewi Sinawang, Elizabeth Stanley, Matthew Mansi, Raymond G Sierra, Brandon Hayes, Xianming Tan, Demir Akin, Bin Chen, Utkan Demirci, Imran Rizvi","doi":"10.1111/php.14014","DOIUrl":"https://doi.org/10.1111/php.14014","url":null,"abstract":"<p><p>Over 75% percent of ovarian cancer patients are diagnosed with advanced-stage disease characterized by unresectable intraperitoneal dissemination and the presence of ascites, or excessive fluid build-up within the abdomen. Conventional treatments include cytoreductive surgery followed by multi-line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced-stage ovarian cancer will relapse and succumb to platinum-resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial-to-mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS-induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro-drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence-based biomarker of FSS-induced platinum resistance. Additionally, this study investigates the efficacy of PpIX-enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov-3 and NIH:OVCAR-3 cells, two representative cell lines for high-grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA-PpIX-mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX-mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence-based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The study aimed to directly assess the ocular safety of 222-nm far-ultraviolet-C (UVC) irradiation in humans, given the limited clinical trials in this area. This wavelength offers the potential for safe and effective microbial inactivation in occupied spaces, but its safety profile for human eyes requires thorough investigation. This prospective, interventional study involved five subjects aged 29-47 years, who were exposed to 222-nm UVC at doses of 22, 50, and 75 mJ/cm2. The subjects were monitored using custom-made glasses with a UV-cut filter on one eye to serve as a control. UVC irradiation was conducted using a KrCl excimer lamp, and ocular examinations were performed prior to exposure, 24 h post-exposure, and at 1, 3, and 6 months. Parameters assessed included visual acuity, refractive error, corneal endothelial density, corneal erosion scores, and conjunctival hyperemia scores. The study found no clinically significant photokeratitis or long-term eye damage across the five subjects, even at the highest dose of 75 mJ/cm2. Temporary ocular discomfort, including sensations of dryness and epiphora, was reported, but these symptoms subsided within hours after irradiation. The findings indicate that 222-nm far-UVC irradiation up to 75 mJ/cm2 does not cause "clinically significant photokeratitis" or long-term ocular damage, though it may induce temporary discomfort. This supports the safe use of 222-nm UVC for germicidal applications in occupied environments, providing a basis for revised safety guidelines.
{"title":"Interventional human ocular safety experiments for 222-nm far-ultraviolet-C lamp irradiation.","authors":"Kazunobu Sugihara, Sachiko Kaidzu, Masahiro Sasaki, Masaki Tanito","doi":"10.1111/php.14016","DOIUrl":"https://doi.org/10.1111/php.14016","url":null,"abstract":"<p><p>The study aimed to directly assess the ocular safety of 222-nm far-ultraviolet-C (UVC) irradiation in humans, given the limited clinical trials in this area. This wavelength offers the potential for safe and effective microbial inactivation in occupied spaces, but its safety profile for human eyes requires thorough investigation. This prospective, interventional study involved five subjects aged 29-47 years, who were exposed to 222-nm UVC at doses of 22, 50, and 75 mJ/cm<sup>2</sup>. The subjects were monitored using custom-made glasses with a UV-cut filter on one eye to serve as a control. UVC irradiation was conducted using a KrCl excimer lamp, and ocular examinations were performed prior to exposure, 24 h post-exposure, and at 1, 3, and 6 months. Parameters assessed included visual acuity, refractive error, corneal endothelial density, corneal erosion scores, and conjunctival hyperemia scores. The study found no clinically significant photokeratitis or long-term eye damage across the five subjects, even at the highest dose of 75 mJ/cm<sup>2</sup>. Temporary ocular discomfort, including sensations of dryness and epiphora, was reported, but these symptoms subsided within hours after irradiation. The findings indicate that 222-nm far-UVC irradiation up to 75 mJ/cm<sup>2</sup> does not cause \"clinically significant photokeratitis\" or long-term ocular damage, though it may induce temporary discomfort. This supports the safe use of 222-nm UVC for germicidal applications in occupied environments, providing a basis for revised safety guidelines.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}