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Molecules (Basel, Switzerland) Aug 20231,4-Benzothiazines are the main building blocks of the naturally occurring pheomelanin pigments, and their chromophoric properties have been strongly related to the... (Review)
Review
1,4-Benzothiazines are the main building blocks of the naturally occurring pheomelanin pigments, and their chromophoric properties have been strongly related to the well-known phototoxicity of these pigments, partly responsible for the high incidence of melanoma and other skin cancers in red-haired people. However, some peculiar features of the 1,4-benzothiazine chromophore could be functionally exploited in several sectors. Within this context, in this perspective, an overview of the very recently reported applications of the 1,4-benzothiazine chromophore in pH sensing, filter permeability control, smart packaging, electrochromic device fabrication, bioimaging, photocatalysis, and HPLC detection systems is provided, together with a brief presentation of recently developed synthetic approaches to the 1,4-benzothiazine scaffold, with the aim of emphasizing the still-undervalued multifunctional opportunities offered by this class of compounds.
Topics: Humans; Chromatography, High Pressure Liquid; Dermatitis, Phototoxic; Melanoma; Permeability
PubMed: 37687069
DOI: 10.3390/molecules28176237 -
Journal of Patient-reported Outcomes Nov 2023Erythropoietic protoporphyria is a rare, inherited disorder presenting in early childhood with severe, painful phototoxicity. EPP has significant impacts on...
BACKGROUND
Erythropoietic protoporphyria is a rare, inherited disorder presenting in early childhood with severe, painful phototoxicity. EPP has significant impacts on health-related quality of life, though there is variable disease severity. Accurately capturing how much time individuals with EPP can spend outdoors before they develop symptoms is critical to understanding HRQoL and measuring therapeutic response. Therefore, the goal of this study was to develop a comprehensive and content valid sun exposure diary to assess the efficacy of new therapies in individuals with EPP.
METHODS
Qualitative interviews were conducted with adult and adolescent EPP participants, as well as five clinical experts, to obtain their input on the content of an existing sun exposure diary. Revisions to the diary were made based on evidence generated in cognitive debriefing interviews analyzed in eight consecutive groups of EPP participant.
RESULTS
Interviews were conducted with 17 adults and 6 adolescents with EPP. The average age of adults was 40 years and of adolescents was 14 years. Clinical experts thought the original diary needed clarification on the description of symptoms, how time outdoors was captured, and the distinction between direct vs. indirect sunlight. Participants with EPP also noted these items needed revision, and that the distinction between prodromal symptoms and full reaction symptoms should be clarified. In the final diary version, participants with EPP found most items to be clear and easy to complete/think about. Seventy-six percent of participants (13/17) asked thought the diary was easy to complete. The remainder thought the majority of the diary was easy to complete with the exception of select questions.
CONCLUSIONS
Evaluating a new treatment for EPP requires accurately capturing time in sunlight and symptoms in this unique disorder. The newly developed sun exposure diary is content valid and can be used to assess important aspects of symptoms and daily life and therefore evaluate clinically meaningful therapeutic response.
Topics: Child, Preschool; Adolescent; Adult; Humans; Protoporphyria, Erythropoietic; Quality of Life; Sunlight; Patients; Dermatitis, Phototoxic; Rare Diseases
PubMed: 37982964
DOI: 10.1186/s41687-023-00655-y -
Scientific Data Oct 2023Detecting and tracking multiple moving objects in a video is a challenging task. For living cells, the task becomes even more arduous as cells change their morphology...
Detecting and tracking multiple moving objects in a video is a challenging task. For living cells, the task becomes even more arduous as cells change their morphology over time, can partially overlap, and mitosis leads to new cells. Differently from fluorescence microscopy, label-free techniques can be easily applied to almost all cell lines, reducing sample preparation complexity and phototoxicity. In this study, we present ALFI, a dataset of images and annotations for label-free microscopy, made publicly available to the scientific community, that notably extends the current panorama of expertly labeled data for detection and tracking of cultured living nontransformed and cancer human cells. It consists of 29 time-lapse image sequences from HeLa, U2OS, and hTERT RPE-1 cells under different experimental conditions, acquired by differential interference contrast microscopy, for a total of 237.9 hours. It contains various annotations (pixel-wise segmentation masks, object-wise bounding boxes, tracking information). The dataset is useful for testing and comparing methods for identifying interphase and mitotic events and reconstructing their lineage, and for discriminating different cellular phenotypes.
Topics: Humans; Cell Cycle; Cell Tracking; HeLa Cells; Image Processing, Computer-Assisted; Microscopy, Fluorescence; Time-Lapse Imaging
PubMed: 37794110
DOI: 10.1038/s41597-023-02540-1 -
BioRxiv : the Preprint Server For... Jan 2024Being able to quantify the phototoxicity of dyes and drugs in live cells allows biologists to better understand cell responses to exogenous stimuli during imaging. This...
UNLABELLED
Being able to quantify the phototoxicity of dyes and drugs in live cells allows biologists to better understand cell responses to exogenous stimuli during imaging. This capability further helps to design fluorescent labels with lower phototoxicity and drugs with better efficacy. Conventional ways to evaluate cellular phototoxicity rely on late-stage measurements of individual or different populations of cells. Here, we developed a quantitative method using intracellular microtubule polymerization as a rapid and sensitive marker to quantify early-stage phototoxicity. Implementing this method, we assessed the photosensitization induced by organelle dyes illuminated with different excitation wavelengths. Notably, fluorescent markers targeting mitochondria, nuclei, and endoplasmic reticulum exhibited diverse levels of phototoxicity. Furthermore, leveraging a real-time precision opto-control technology allowed us to evaluate the synergistic effect of light and dyes on specific organelles. Studies in hypoxia revealed enhanced phototoxicity of Mito-Tracker Red CMXRos that is not correlated with the generation of reactive oxygen species but a different deleterious pathway in low oxygen conditions.
TEASER
Microtubule dynamics in live cells allow quantification of cellular phototoxicity of fluorescent dyes in various conditions.
PubMed: 38293099
DOI: 10.1101/2024.01.17.576021 -
Frontiers in Bioengineering and... 2023Fluorescent visualization of hydrogen peroxide in the tumor microenvironment (TME) is conducive to predicting malignant prognosis after chemotherapy. Two photon...
Fluorescent visualization of hydrogen peroxide in the tumor microenvironment (TME) is conducive to predicting malignant prognosis after chemotherapy. Two photon microscopy has been employed for hydrogen peroxide detection owing to its advantages of deep penetration and low phototoxicity. In this study, a two-photon fluorescent probe (TPFP) was protected by mesoporous silica nanoparticles (MSNs) and masked by cloaking the cancer cell membranes (CM), forming a tumor-targeted bioactive nanoprobe, termed MSN@TPFP@CM. This multifunctional nanoprobe allowed for the effective and selective detection of excessive hydrogen peroxide production in chemotherapeutic Etoposide (VP-16)-challenged tumor cells using two-photon microscopy. After specific accumulation in tumors, VP-16-MSN@TPFP@CM monitored tumor-specific hydrogen peroxide levels and revealed a positive correlation between oxidative stress in the TME and chemotherapy-exacerbated malignant prognosis. Given the recent translation of fluorescent imaging into early clinical trials and the high biocompatibility of bioactive nanoprobes, our approach may pave the way for specific imaging of oxidative stress in solid tumors after treatment and provide a promising technology for malignant prognosis predictions.
PubMed: 37635993
DOI: 10.3389/fbioe.2023.1226680 -
Frontiers in Physiology 2024Solar radiation can cause damage to the skin, and the use of sunscreens is one of the main protective measures. However, photounstable ultraviolet (UV) filters can...
Solar radiation can cause damage to the skin, and the use of sunscreens is one of the main protective measures. However, photounstable ultraviolet (UV) filters can generate photoproducts and reactive oxygen species (ROS). Adding antioxidants, such as resveratrol, to enhance the action of UV filters in sunscreens is an interesting strategy for reducing the damage caused by UV radiation exposure. However, new compounds must have their stability, safety and efficacy guaranteed. Avobenzone, a commonly used UV filter, stands out as a promising candidate for structural modification to enhance its stability. Its molecular hybridization with other UV filters and antioxidants can lead to safer and more effective compounds. In this study, the photoprotective and antioxidant potential of a derivative of avobenzone, hybridized with resveratrol's molecule, was evaluated using models of cells in monolayer and reconstructed human skin (RHS). Phototoxic potential was assessed using fibroblasts, while the antioxidant activity was measured using the DCFH-DA probe in HaCaT keratinocytes and in-house RHS. The derivative exhibited UV absorption and demonstrated photostability. It did not exhibit any phototoxic nor photoreactivity potential. Additionally, it was able to photo stabilize a combination of photounstable UV filters, avobenzone and octyl methoxycinnamate, and to reduce their phototoxic potential. In terms of antioxidant activity, the derivative successfully protected against UVA-induced ROS production in the HaCaT keratinocytes model, showing statistical equivalence to the antioxidant control, quercetin (10 μg/mL). Furthermore, experiments conducted in the RHS model demonstrated a significant reduction of 30.7% in ROS generation compared to the irradiated control. This study demonstrated that structural modifications of avobenzone can lead to the development of a broad spectrum (absorbing UVB and UVA II radiation, as well as a portion of the UVA I radiation), non-phototoxic, non-photoreactive and photostable derivative for sunscreen and anti-aging formulations. This derivative enhances protection against oxidative stress induced by UV radiation and improves the effectiveness of sun protection. In addition to the monolayer model, the use of a standardized in-house RHS model was highly relevant for evaluating the effects of UV radiation and skin aging. This model closely mimics human physiological conditions and enables the testing of new compounds and the investigation of protective mechanisms against skin damage.
PubMed: 38487263
DOI: 10.3389/fphys.2024.1347414 -
Molecular Biology of the Cell Sep 2023The dynamics of living cells can be studied by live-cell fluorescence microscopy. However, this requires the use of excessive light energy to obtain good signal-to-noise...
The dynamics of living cells can be studied by live-cell fluorescence microscopy. However, this requires the use of excessive light energy to obtain good signal-to-noise ratio, which can then photobleach fluorochromes, and more worrisomely, lead to phototoxicity. Upon light excitation, noble metal nanoparticles such as silver nanoparticles (AgNPs) generate plasmons, which can then amplify excitation in direct proximity of the nanoparticle's surface and couple to the oscillating dipole of nearby radiating fluorophores, modifying their rate of emission and thus, enhancing their fluorescence. Here, we show that AgNPs fed to cells to accumulate within lysosomes enhanced the fluorescence of lysosome-targeted Alexa488-conjugated dextran, BODIPY-cholesterol, and DQ-BSA. Moreover, AgNP increased the fluorescence of GFP fused to the cytosolic tail of LAMP1, showing that metal enhanced fluorescence can occur across the lysosomal membrane. The inclusion of AgNPs in lysosomes did not disturb lysosomal properties such as lysosomal pH, degradative capacity, autophagy and autophagic flux, and membrane integrity, though AgNP seemed to increase basal lysosome tubulation. Importantly, by using AgNP, we could track lysosome motility with reduced laser power without damaging and altering lysosome dynamics. Overall, AgNP-enhanced fluorescence may be a useful tool to study the dynamics of the endo-lysosomal pathway while minimizing phototoxicity.
Topics: Silver; Metal Nanoparticles; Microscopy, Fluorescence; Lysosomes
PubMed: 37405751
DOI: 10.1091/mbc.E22-06-0200 -
Indian Journal of Pharmacology Jan 2024Cosmeceuticals are topically applied cosmetic products containing a biologically active ingredient with a pharmaceutical effect that improves, nourishes, and treats the... (Review)
Review
Cosmeceuticals are topically applied cosmetic products containing a biologically active ingredient with a pharmaceutical effect that improves, nourishes, and treats the skin appearance. The trend of cosmeceuticals began during the mid-20th century due to its potent ingredients with therapeutic effects for various skin ailments. Even though there is a great advancement in cosmetics, which shows the risk of cosmetic linked melanoma, endocrine disorders, and birth defects which was one in 1500 people during 1935 have increased to one in 75 people in 2000. Hence, as a part of reducing the harmful effect, natural ingredients were added to the formulation to give the pharmaceutical effect. Thus, natural/herbal cosmeceuticals were introduced. Due to the awareness of the side effects such as photo-toxicity, mutagenicity, irritation by these synthetic products, people started preferring herbal/natural cosmetic products. Moreover, natural cosmeceuticals were proven to be effective against various dermatological conditions as well as have fewer side effects marked the natural/herbal cosmeceuticals in the market. Unlike a drug, cosmeceutical products undergo safety, toxicity, and efficacy tests, but these are not classified under Food and Drug Administration. This review will give an insight into different natural ingredients used in natural/herbal cosmeceutical formulation and their function challenges faced during formulation, advantages of natural cosmeceuticals over regular cosmeceuticals, and regulatory aspects in India.
Topics: Humans; Cosmeceuticals; Cosmetics; Skin; Pharmaceutical Preparations; Pharmaceutical Vehicles; Biological Products
PubMed: 38454588
DOI: 10.4103/ijp.ijp_244_21 -
BioRxiv : the Preprint Server For... Jul 2023Structured illumination microscopy (SIM) is a versatile super-resolution technique known for its compatibility with a wide range of probes and fast implementation. While...
Structured illumination microscopy (SIM) is a versatile super-resolution technique known for its compatibility with a wide range of probes and fast implementation. While 3D SIM is capable of achieving a spatial resolution of ∼120 nm laterally and ∼300 nm axially, attempting to further enhance the resolution through methods such as nonlinear SIM or 4-beam SIM introduces complexities in optical configurations, increased phototoxicity, and reduced temporal resolution. Here, we have developed a novel method that combines SIM with augmented super-resolution radial fluctuations (aSRRF) utilizing a single image through image augmentation. By applying aSRRF reconstruction to SIM images, we can enhance the SIM resolution to ∼50 nm isotopically, without requiring any modifications to the optical system or sample acquisition process. Additionaly, we have incorporated the aSRRF approach into an ImageJ plugin and demonstrated its versatility across various fluorescence microscopy images, showcasing a remarkable two-fold resolution increase.
PubMed: 37786707
DOI: 10.1101/2023.07.05.547885 -
Discover Nano Apr 2024Modern imaging strategies are paramount to studying living systems such as cells, bacteria, and fungi and their response to pathogens, toxicants, and nanomaterials (NMs)... (Review)
Review
Modern imaging strategies are paramount to studying living systems such as cells, bacteria, and fungi and their response to pathogens, toxicants, and nanomaterials (NMs) as modulated by exposure and environmental factors. The need to understand the processes and mechanisms of damage, healing, and cell survivability of living systems continues to motivate the development of alternative imaging strategies. Of particular interest is the use of label-free techniques (microscopy procedures that do not require sample staining) that minimize interference of biological processes by foreign marking substances and reduce intense light exposure and potential photo-toxicity effects. This review focuses on the synergic capabilities of atomic force microscopy (AFM) as a well-developed and robust imaging strategy with demonstrated applications to unravel intimate details in biomedical applications, with the label-free, fast, and enduring Holotomographic Microscopy (HTM) strategy. HTM is a technique that combines holography and tomography using a low intensity continuous illumination laser to investigate (quantitatively and non-invasively) cells, microorganisms, and thin tissue by generating three-dimensional (3D) images and monitoring in real-time inner morphological changes. We first review the operating principles that form the basis for the complementary details provided by these techniques regarding the surface and internal information provided by HTM and AFM, which are essential and complimentary for the development of several biomedical areas studying the interaction mechanisms of NMs with living organisms. First, AFM can provide superb resolution on surface morphology and biomechanical characterization. Second, the quantitative phase capabilities of HTM enable superb modeling and quantification of the volume, surface area, protein content, and mass density of the main components of cells and microorganisms, including the morphology of cells in microbiological systems. These capabilities result from directly quantifying refractive index changes without requiring fluorescent markers or chemicals. As such, HTM is ideal for long-term monitoring of living organisms in conditions close to their natural settings. We present a case-based review of the principal uses of both techniques and their essential contributions to nanomedicine and nanotoxicology (study of the harmful effects of NMs in living organisms), emphasizing cancer and infectious disease control. The synergic impact of the sequential use of these complementary strategies provides a clear drive for adopting these techniques as interdependent fundamental tools.
PubMed: 38594446
DOI: 10.1186/s11671-024-04003-x