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Journal of Photochemistry and... Feb 2024Photosensitivity to structurally diverse drugs is a common but under-reported adverse cutaneous reaction and can be classified as phototoxic or photoallergic. Phototoxic...
Photosensitivity to structurally diverse drugs is a common but under-reported adverse cutaneous reaction and can be classified as phototoxic or photoallergic. Phototoxic reactions occur when the skin is exposed to sunlight after administering topical or systemic medications that exhibit photosensitizing activity. These reactions depend on the dose of medication, degree of exposure to ultraviolet light, type of ultraviolet light, and sufficient skin distribution volume. Accurate prediction of the incidence and phototoxic response severity is challenging due to a paucity of literature, suggesting that phototoxicity may be more frequent than reported. This paper reports an extensive literature review on phototoxic drugs; the review employed pre-determined search criteria that included meta-analyses, systematic reviews, literature reviews, and case reports freely available in full text. Additional reports were identified from reference sections that contributed to the understanding of phototoxicity. The following drugs and/or drug classes are discussed: amiodarone, voriconazole, chlorpromazine, doxycycline, fluoroquinolones, hydrochlorothiazide, nonsteroidal anti-inflammatory drugs, and vemurafenib. In reviewing phototoxic skin reactions, this review highlights drug molecular structures, their reactive pathways, and, as there is a growing association between photosensitizing drugs and the increasing incidence of skin cancer, the consequential long-term implications of photocarcinogenesis.
PubMed: 38389933
DOI: 10.1016/j.jpap.2023.100221 -
Alternatives To Laboratory Animals :... Jun 2024Phototoxicity testing is crucial for evaluating the potential harmful effects of pharmaceuticals and chemicals on human skin when exposed to sunlight. Traditional...
Phototoxicity testing is crucial for evaluating the potential harmful effects of pharmaceuticals and chemicals on human skin when exposed to sunlight. Traditional models involving mice, rats, guinea pigs, as well as assays such as the 3T3 Neutral Red Uptake phototoxicity assay and methods based on the use of reconstructed human epidermis, have been established for phototoxicity testing. While these approaches are extremely valuable, they are costly in terms of both time and resources. Consequently, approaches based on the use of predictive software tools can offer more rapid and cost-effective phototoxicity screening solutions. With this goal in mind, the current study evaluated two tools - Derek Nexus 6.1.0/Derek Knowledge Base 2020 1.0 (Lhasa Limited, UK) and the QSAR Toolbox (v 4.5) developed by the Organisation for Economic Co-operation and Development (OECD) - for their capacity to predict the phototoxicity of several substances from diverse classes. Derek Nexus and the QSAR Toolbox were both found to be very useful for predicting the phototoxicity of drugs and other chemicals. Derek Nexus predicted phototoxicity of the compounds, with a sensitivity of 63%, specificity of 93%, Positive Predictive Values of 90% and Negative Predictive Value of 69%, overall accuracy of 77% and balanced accuracy of 78%. The QSAR Toolbox achieved sensitivity of 73%, specificity of 85%, Positive Predictive Value of 85% and Negative Predictive Value of 74%, overall accuracy of 79% and balanced accuracy of 79%. The results show that Derek Nexus and the QSAR Toolbox can be usefully incorporated in the workflow of phototoxicity testing for pharmaceuticals and chemicals.
PubMed: 38910363
DOI: 10.1177/02611929241256040 -
Journal of the American Academy of... Dec 2023Erythropoietic protoporphyria and X-linked protoporphyria are rare genetic photodermatoses. Limited expertise with these disorders among physicians leads to diagnostic...
Erythropoietic protoporphyria and X-linked protoporphyria are rare genetic photodermatoses. Limited expertise with these disorders among physicians leads to diagnostic delays. Here, we present evidence-based consensus guidelines for the diagnosis, monitoring, and management of erythropoietic protoporphyria and X-linked protoporphyria. A systematic literature review was conducted, and reviewed among subcommittees of experts, divided by topic. Consensus on guidelines was reached within each subcommittee and then among all members of the committee. The appropriate biochemical and genetic testing to establish the diagnosis is reviewed in addition to the interpretation of results. Prevention of symptoms, management of acute phototoxicity, and pharmacologic and nonpharmacologic treatment options are discussed. The importance of ongoing monitoring for liver disease, iron deficiency, and vitamin D deficiency is discussed with management guidance. Finally, management of pregnancy and surgery and the safety of other therapies are summarized. We emphasize that these are multisystemic disorders that require longitudinal monitoring. These guidelines provide a structure for evidence-based diagnosis and management for practicing physicians. Early diagnosis and management of these disorders are essential, particularly given the availability of new and emerging therapies.
Topics: Humans; Dermatitis, Phototoxic; Genetic Diseases, X-Linked; Liver Diseases; Protoporphyria, Erythropoietic; Practice Guidelines as Topic
PubMed: 36041558
DOI: 10.1016/j.jaad.2022.08.036 -
Journal of Biophotonics Sep 2023Since its first demonstration over 100 years ago, scattering-based light-sheet microscopy has recently re-emerged as a key modality in label-free tissue imaging and...
Since its first demonstration over 100 years ago, scattering-based light-sheet microscopy has recently re-emerged as a key modality in label-free tissue imaging and cellular morphometry; however, scattering-based light-sheet imaging with subcellular resolution remains an unmet target. This is because related approaches inevitably superimpose speckle or granular intensity modulation on to the native subcellular features. Here, we addressed this challenge by deploying a time-averaged pseudo-thermalized light-sheet illumination. While this approach increased the lateral dimensions of the illumination sheet, we achieved subcellular resolving power after image deconvolution. We validated this approach by imaging cytosolic carbon depots in yeast and bacteria with increased specificity, no staining, and ultralow irradiance levels. Overall, we expect this scattering-based light-sheet microscopy approach will advance single, live cell imaging by conferring low-irradiance and label-free operation towards eradicating phototoxicity.
Topics: Microscopy, Fluorescence; Cytosol
PubMed: 37287076
DOI: 10.1002/jbio.202300068 -
Journal of Controlled Release :... Jul 2023Phototherapy (PT), including photodynamic therapy (PDT) and photothermal therapy (PTT), has recently achieved significant advances in antitumor and antiinfection... (Review)
Review
Phototherapy (PT), including photodynamic therapy (PDT) and photothermal therapy (PTT), has recently achieved significant advances in antitumor and antiinfection therapy. Sonodynamic therapy (SDT), as a novel noninvasive therapy with a deeper penetration depth (>8 cm), fewer side effects and non-phototoxicity than PT, has drawn much attention in recent years. However, both PT and SDT have intrinsic limitations. By combining PT with SDT, the dualmodel therapy with advanced sensitizers overcome the intrinsic limitations and show higher efficacy than traditional monotherapy. Moreover, the photo-diagnosis modality could be easily integrated into synergistic therapy so that the sensitizer acts as a tracer for fluorescence/photoacoustic imaging, and the treatment process is visualized in a way that SDT combined with other therapies cannot achieve. This review summarizes the advanced sensitizers and the application of combination therapy, and explores the improvement strategies for promoting clinical transformation.
Topics: Humans; Neoplasms; Phototherapy; Photochemotherapy; Combined Modality Therapy; Ultrasonic Therapy
PubMed: 37286136
DOI: 10.1016/j.jconrel.2023.05.041 -
Journal of Molecular Biology Dec 2023Optogenetics has emerged as a powerful tool for spatiotemporal control of biological processes. Near-infrared (NIR) light, with its low phototoxicity and deep tissue...
Optogenetics has emerged as a powerful tool for spatiotemporal control of biological processes. Near-infrared (NIR) light, with its low phototoxicity and deep tissue penetration, holds particular promise. However, the optogenetic control of polypeptide bond formation has not yet been developed. In this study, we introduce a NIR optogenetic module for conditional protein splicing (CPS) based on the gp41-1 intein. We optimized the module to minimize background signals in the darkness and to maximize the contrast between light and dark conditions. Next, we engineered a NIR CPS gene expression system based on the protein ligation of a transcription factor. We applied the NIR CPS for light-triggered protein cleavage to activate gasdermin D, a pore-forming protein that induces pyroptotic cell death. Our NIR CPS optogenetic module represents a promising tool for controlling molecular processes through covalent protein linkage and cleavage.
Topics: Protein Splicing; Optogenetics; Inteins; Gene Expression Regulation
PubMed: 37949312
DOI: 10.1016/j.jmb.2023.168360 -
Natural Products and Bioprospecting Nov 2023Mushrooms have been utilized by humans for thousands of years due to their medicinal and nutritional properties. They are a crucial natural source of bioactive secondary... (Review)
Review
Mushrooms have been utilized by humans for thousands of years due to their medicinal and nutritional properties. They are a crucial natural source of bioactive secondary metabolites, and recent advancements have led to the isolation of several alkynyl-containing compounds with potential medicinal uses. Despite their relatively low abundance, naturally occurring alkynyl compounds have attracted considerable attention due to their high reactivity. Bioactivity studies have shown that alkynyl compounds exhibit significant biological and pharmacological activities, including antitumor, antibacterial, antifungal, insecticidal, phototoxic, HIV-inhibitory, and immunosuppressive properties. This review systematically compiles 213 alkynyl-containing bioactive compounds isolated from mushrooms since 1947 and summarizes their diverse biological activities, focusing mainly on cytotoxicity and anticancer effects. This review serves as a detailed and comprehensive reference for the chemical structures and bioactivity of alkynyl-containing secondary metabolites from mushrooms. Moreover, it provides theoretical support for the development of chemical constituents containing alkynyl compounds in mushrooms based on academic research and theory.
PubMed: 37946001
DOI: 10.1007/s13659-023-00416-w -
Tissue Engineering. Part B, Reviews Dec 2023Three-dimensional (3D) bioprinting, or additive manufacturing, is a rapid fabrication technique with the foremost objective of creating biomimetic tissue and organ... (Review)
Review
Three-dimensional (3D) bioprinting, or additive manufacturing, is a rapid fabrication technique with the foremost objective of creating biomimetic tissue and organ replacements in hopes of restoring normal tissue function and structure. Generating the engineered organs with an infrastructure that is similar to that of the real organs can be beneficial to simulate the functional organs that work inside our bodies. Photopolymerization-based 3D bioprinting, or photocuring, has emerged as a promising method in engineering biomimetic tissues due to its simplicity, and noninvasive and spatially controllable approach. In this review, we investigated types of 3D printers, mainstream materials, photoinitiators, phototoxicity, and selected tissue engineering applications of 3D photopolymerization bioprinting.
Topics: Humans; Tissue Engineering; Bioprinting; Polymers; Printing, Three-Dimensional; Tissue Scaffolds; Biocompatible Materials
PubMed: 37335218
DOI: 10.1089/ten.TEB.2023.0072 -
The Science of the Total Environment Dec 2023Waste plastics enter the environment (water, soil, and atmosphere) and degrade into micro- and nano-plastics (MNPs) through physical, chemical, or biological processes.... (Review)
Review
Waste plastics enter the environment (water, soil, and atmosphere) and degrade into micro- and nano-plastics (MNPs) through physical, chemical, or biological processes. MNPs are ubiquitous in the environment and inevitably interact with terrestrial plants. Terrestrial plants have become important potential sinks, and subsequently, the sources of MNPs. At present, many studies have reported the effects of MNPs on plant physiology, biochemistry, and their phototoxicity. However, the source, detection method, and the absorption process of MNPs in terrestrial plants have not been systematically studied. In order to better understand the continuous process of MNPs entering terrestrial plants, this review introduces the sources and analysis methods of MNPs in terrestrial plants. The uptake pathways of MNPs in terrestrial plants and their influencing factors were systematically summarized. Meanwhile, the transport pathways and the accumulation of MNPs in different plant organs (roots, stems, leaves, calyxes, and fruits) were explored. Finally, the transfer of MNPs through food chains to humans and their health risks were discussed. The aim of this work is to provide significant theoretical knowledge to understand the uptake, transport, and accumulation of MNPs in terrestrial plants and the potential health risks associated with their transfer to humans through food chain.
Topics: Humans; Plastics; Food Chain; Microplastics; Plants; Soil; Water Pollutants, Chemical
PubMed: 37544454
DOI: 10.1016/j.scitotenv.2023.166045 -
Advanced Materials (Deerfield Beach,... Jul 2023Cancer-associated fibroblasts (CAFs) are the major components of the tumor-associated matrix and play an important role in tumor progression and immunosuppression....
Cancer-associated fibroblasts (CAFs) are the major components of the tumor-associated matrix and play an important role in tumor progression and immunosuppression. Therefore, precise theranostics of CAFs are beneficial for CAFs-targeted therapies. However, imaging agents enabling precise theranostics of CAFs have been rarely exploited. To tackle this issue, a molecular pro-theranostic probe (FMP) with activatable fluorescence, photoacoustic (PA) imaging, and photodynamic therapy (PDT) is developed in response to fibroblast activation protein α (FAPα) overexpressed in >90% types of CAFs and some tumor cells. Attributed to efficient activatable phototoxicity toward CAFs and tumor cells, together with activated immunogenic cell death (ICD), complete tumor regression of primary tumors and abscopal effect of distant tumors are observed in a 4T1-tumor-bearing mice model. By integration with PD-L1 checkpoint blockade immunotherapy, enhanced systemic immune responses are evoked to obtain long-lasting tumor suppression of both primary and distant tumors as well as arrest systemic cancer metastasis in living mice.
Topics: Animals; Mice; Precision Medicine; Cell Line, Tumor; Photochemotherapy; Immunotherapy; Tumor Microenvironment; Neoplasms
PubMed: 37086426
DOI: 10.1002/adma.202211485