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Cureus Apr 2024Pseudoporphyria is an uncommon dermatosis resembling porphyria cutanea tarda (PCT). The exclusion of true porphyria, especially PCT, is critically essential for...
Pseudoporphyria is an uncommon dermatosis resembling porphyria cutanea tarda (PCT). The exclusion of true porphyria, especially PCT, is critically essential for diagnosing pseudoporphyria. It has an unknown underlying pathophysiology with a normal or near-normal porphyrin profile. Pseudoporphyria has been associated with chronic renal failure and hemodialysis, medications, and tanning beds. In drug-induced pseudoporphyria cases, eliminating the suspected photosensitizing drug improves the disease typically within weeks to months (on average eight weeks). In genetically predisposed individuals, phototoxic metabolites may trigger the development of skin fragility, bullae, milia, and scarring on the dorsum of the hands and other sun-exposed areas. Wearing a broad-spectrum sunscreen and maintaining strict ultraviolet protection is essential in cases of pseudoporphyria. We report the case of a 20-year-old male who presented to us with complaints of photosensitivity and multiple erosions with irregular scars over photo-exposed areas involving the dorsum of the hands and face predominantly. The patient was evaluated further to determine the underlying cause. A wood's lamp examination of the urine was done, which did not show fluorescence. Based on clinical and laboratory findings, the diagnosis of pseudoporphyria was made, and the patient was started on the oral antimalarial agent hydroxychloroquine sulfate with strict sun protection.
PubMed: 38707054
DOI: 10.7759/cureus.57574 -
Cell Reports May 2024Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment...
Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment epithelium (RPE) and Müller glia (MG), but the relative functional importance of these two cellular pools is debated. Here, we report RPE- and MG-specific CRALBP knockout (KO) mice and examine their photoreceptor and visual cycle function. Bulk visual chromophore regeneration in RPE-KO mice is 15-fold slower than in controls, accounting for their delayed rod dark adaptation and protection against retinal phototoxicity, whereas MG-KO mice have normal bulk visual chromophore regeneration and retinal light damage susceptibility. Cone pigment regeneration is significantly impaired in RPE-KO mice but mildly affected in MG-KO mice, disclosing an unexpectedly strong reliance of cone photoreceptors on the RPE-based visual cycle. These data reveal a dominant role for RPE-CRALBP in supporting rod and cone function and highlight the importance of RPE cell targeting for CRALBP gene therapies.
Topics: Animals; Mice; Carrier Proteins; Ependymoglial Cells; Mice, Inbred C57BL; Mice, Knockout; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Retinal Pigments; Retinal Rod Photoreceptor Cells; Male; Female
PubMed: 38676924
DOI: 10.1016/j.celrep.2024.114143 -
Pharmaceuticals (Basel, Switzerland) Apr 2024Melanins are biopolymeric pigments formed by a multi-step oxidation process of tyrosine in highly specialized cells called melanocytes. Melanin pigments are mainly found... (Review)
Review
Melanins are biopolymeric pigments formed by a multi-step oxidation process of tyrosine in highly specialized cells called melanocytes. Melanin pigments are mainly found in the skin, iris, hair follicles, and inner ear. The photoprotective properties of melanin biopolymers have been linked to their perinuclear localization to protect DNA, but their ability to scavenge metal ions and antioxidant properties has also been noted. Interactions between drugs and melanins are of clinical relevance. The formation of drug-melanin complexes can affect both the efficacy of pharmacotherapy and the occurrence of adverse effects such as phototoxic reactions and discoloration. Because the amount and type of melanin synthesized in the body is subject to multifactorial regulation-determined by both internal factors such as genetic predisposition, inflammation, and hormonal balance and external factors such as contact with allergens or exposure to UV radiation-different effects on the melanogenesis process can be observed. These factors can directly influence skin pigmentation disorders, resulting in hypopigmentation or hyperpigmentation of a genetic or acquired nature. In this review, we will present information on melanocyte biology, melanogenesis, and the multifactorial influence of melanin on pharmacological parameters during pharmacotherapy. In addition, the types of skin color disorders, with special emphasis on the process of their development, symptoms, and methods of treatment, are presented in this article.
PubMed: 38675481
DOI: 10.3390/ph17040521 -
Cells Apr 2024STED nanoscopy allows for the direct observation of dynamic processes in living cells and tissues with diffraction-unlimited resolution. Although fluorescent proteins...
STED nanoscopy allows for the direct observation of dynamic processes in living cells and tissues with diffraction-unlimited resolution. Although fluorescent proteins can be used for STED imaging, these labels are often outperformed in photostability by organic fluorescent dyes. This feature is especially crucial for time-lapse imaging. Unlike fluorescent proteins, organic fluorophores cannot be genetically fused to a target protein but require different labeling strategies. To achieve simultaneous imaging of more than one protein in the interior of the cell with organic fluorophores, bioorthogonal labeling techniques and cell-permeable dyes are needed. In addition, the fluorophores should preferentially emit in the red spectral range to reduce the potential phototoxic effects that can be induced by the STED light, which further restricts the choice of suitable markers. In this work, we selected five different cell-permeable organic dyes that fulfill all of the above requirements and applied them for SPIEDAC click labeling inside living cells. By combining click-chemistry-based protein labeling with other orthogonal and highly specific labeling methods, we demonstrate two-color STED imaging of different target structures in living specimens using different dye pairs. The excellent photostability of the dyes enables STED imaging for up to 60 frames, allowing the observation of dynamic processes in living cells over extended time periods at super-resolution.
Topics: Fluorescent Dyes; Humans; Click Chemistry; HeLa Cells; Microscopy, Fluorescence; Color; Nanotechnology; Biomarkers; Staining and Labeling
PubMed: 38667298
DOI: 10.3390/cells13080683 -
Journal of Lasers in Medical Sciences 2024This in vitro study was conducted to assess the phototoxic effects of curcumin, nano-curcumin, and erythrosine on the viability of in suspension and biofilm forms....
This in vitro study was conducted to assess the phototoxic effects of curcumin, nano-curcumin, and erythrosine on the viability of in suspension and biofilm forms. Various concentrations of curcumin (1.5 g/L, 3 g/L), nano-curcumin (3 g/L), and erythrosine (100 μM/L, 250 μM/L) were examined for their impact on planktonic and biofilm cultures of , either individually or in conjunction with light irradiation (photodynamic therapy or PDT). A blue light-emitting diode (LED) with a central wavelength of 450 nm served as the light source. The results were compared to 0.12% chlorhexidine digluconate (CHX) as the positive control, and a solution containing neither a photosensitizer (PS) nor a light source as the negative control group. The dependent variable was the number of viable microorganisms per experiment (CFU/mL). Antimicrobial PDT caused a significant reduction in the viability of in both planktonic and biofilm forms, compared to the negative control group (<0.05). The highest cell killing was observed in PDT groups with curcumin 3 g/L or erythrosine 250 μmol/L, although the difference with PDT groups using curcumin 1.5 g/L or erythrosine 100 μmol/L was not significant (>0.05). Antimicrobial treatments were more effective against planktonic S. mutans than the biofilm form. PDT with either curcumin 1.5 g/L or erythrosine 100 μmol/L may be suggested as an alternative to CHX to inactivate the bacteria in dental plaque or deep cavities. Nano-curcumin, at the selected concentration, exhibited lower efficacy in killing compared to Curcumin or erythrosine.
PubMed: 38655044
DOI: 10.34172/jlms.2024.07 -
Advanced Science (Weinheim,... Jun 2024The escalating spread of drug-resistant bacteria and viruses is a grave concern for global health. Nucleic acids dominate the drug-resistance and transmission of...
The escalating spread of drug-resistant bacteria and viruses is a grave concern for global health. Nucleic acids dominate the drug-resistance and transmission of pathogenic microbes. Here, imidazolium-type poly(ionic liquid)/porphyrin (PIL-P) based electrospun nanofibrous membrane and its cerium (IV) ion complex (PIL-P-Ce) are developed. The obtained PIL-P-Ce membrane exhibits high and stable efficiency in eradicating various microorganisms (bacteria, fungi, and viruses) and decomposing microbial antibiotic resistance genes and viral nucleic acids under light. The nuclease-mimetic and photocatalytic mechanisms of the PIL-P-Ce are elucidated. Co-infection wound models in mice with methicillin-resistant S. aureus and hepatitis B virus demonstrate that PIL-P-Ce integrate the triple effects of cationic polymer, photocatalysis, and nuclease-mimetic activities. As revealed by proteomic analysis, PIL-P-Ce shows minimal phototoxicity to normal tissues. Hence, PIL-P-Ce has potential as a "green" wound dressing to curb the spread of drug-resistant bacteria and viruses in clinical settings.
Topics: Animals; Mice; Antiviral Agents; Coinfection; Disease Models, Animal; Nanofibers; Anti-Infective Agents; Methicillin-Resistant Staphylococcus aureus; Catalysis; Porphyrins; Ionic Liquids
PubMed: 38647392
DOI: 10.1002/advs.202309590 -
JCI Insight Apr 2024Inherited retinal dystrophies (IRDs) are progressive diseases leading to vision loss. Mutation in the eyes shut homolog (EYS) gene is one of the most frequent causes of...
Inherited retinal dystrophies (IRDs) are progressive diseases leading to vision loss. Mutation in the eyes shut homolog (EYS) gene is one of the most frequent causes of IRD. However, the mechanism of photoreceptor cell degeneration by mutant EYS has not been fully elucidated. Here, we generated retinal organoids from induced pluripotent stem cells (iPSCs) derived from patients with EYS-associated retinal dystrophy (EYS-RD). In photoreceptor cells of RD organoids, both EYS and G protein-coupled receptor kinase 7 (GRK7), one of the proteins handling phototoxicity, were not in the outer segment, where they are physiologically present. Furthermore, photoreceptor cells in RD organoids were vulnerable to light stimuli, and especially to blue light. Mislocalization of GRK7, which was also observed in eys-knockout zebrafish, was reversed by delivering control EYS into photoreceptor cells of RD organoids. These findings suggest that avoiding phototoxicity would be a potential therapeutic approach for EYS-RD.
Topics: Animals; Humans; Eye Proteins; Induced Pluripotent Stem Cells; Light; Mutation; Organoids; Retina; Retinal Dystrophies; Zebrafish
PubMed: 38646933
DOI: 10.1172/jci.insight.174179 -
Scientific Reports Apr 2024Quantitative assessment of cell migration in vitro is often required in fundamental and applied research from different biomedical areas including wound repair, tumor...
Quantitative assessment of cell migration in vitro is often required in fundamental and applied research from different biomedical areas including wound repair, tumor metastasis or developmental biology. A collection of assays has been established throughout the years like the most widely used scratch assay or the so-called barrier assay. It is the principle of these assays to introduce a lesion into an otherwise confluent monolayer in order to study the migration of cells from the periphery into this artificial wound and determine the migration rate from the time necessary for wound closure. A novel assay makes use of photosensitizers doped into a polystyrene matrix. A thin layer of this composite material is coated on the bottom of regular cell culture ware showing perfect biocompatibility. When adherent cells are grown on this coating, resonant excitation of the photosensitizer induces a very local generation of O, which kills the cells residing at the site of illumination. Cells outside the site of illumination are not harmed. When excitation of the photosensitizer is conducted by microscopic illumination, high-precision wounding in any size and geometry is available even in microfluidic channels. Besides proof-of-concept experiments, this study gives further insight into the mechanism of photosensitizer-mediated cell wounding.
Topics: Photosensitizing Agents; Wound Healing; Cell Culture Techniques; Microfluidics; Cell Movement
PubMed: 38643292
DOI: 10.1038/s41598-024-59564-9 -
Journal of Biomedical Optics Jun 2024Three-dimensional quantitative phase imaging (QPI) has rapidly emerged as a complementary tool to fluorescence imaging, as it provides an objective measure of cell...
SIGNIFICANCE
Three-dimensional quantitative phase imaging (QPI) has rapidly emerged as a complementary tool to fluorescence imaging, as it provides an objective measure of cell morphology and dynamics, free of variability due to contrast agents. It has opened up new directions of investigation by providing systematic and correlative analysis of various cellular parameters without limitations of photobleaching and phototoxicity. While current QPI systems allow the rapid acquisition of tomographic images, the pipeline to analyze these raw three-dimensional (3D) tomograms is not well-developed. We focus on a critical, yet often underappreciated, step of the analysis pipeline that of 3D cell segmentation from the acquired tomograms.
AIM
We report the CellSNAP (Cell Segmentation via Novel Algorithm for Phase Imaging) algorithm for the 3D segmentation of QPI images.
APPROACH
The cell segmentation algorithm mimics the gemstone extraction process, initiating with a coarse 3D extrusion from a two-dimensional (2D) segmented mask to outline the cell structure. A 2D image is generated, and a segmentation algorithm identifies the boundary in the plane. Leveraging cell continuity in consecutive -stacks, a refined 3D segmentation, akin to fine chiseling in gemstone carving, completes the process.
RESULTS
The CellSNAP algorithm outstrips the current gold standard in terms of speed, robustness, and implementation, achieving cell segmentation under 2 s per cell on a single-core processor. The implementation of CellSNAP can easily be parallelized on a multi-core system for further speed improvements. For the cases where segmentation is possible with the existing standard method, our algorithm displays an average difference of 5% for dry mass and 8% for volume measurements. We also show that CellSNAP can handle challenging image datasets where cells are clumped and marred by interferogram drifts, which pose major difficulties for all QPI-focused AI-based segmentation tools.
CONCLUSION
Our proposed method is less memory intensive and significantly faster than existing methods. The method can be easily implemented on a student laptop. Since the approach is rule-based, there is no need to collect a lot of imaging data and manually annotate them to perform machine learning based training of the model. We envision our work will lead to broader adoption of QPI imaging for high-throughput analysis, which has, in part, been stymied by a lack of suitable image segmentation tools.
Topics: Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Quantitative Phase Imaging; Algorithms; Optical Imaging
PubMed: 38638450
DOI: 10.1117/1.JBO.29.S2.S22706 -
Journal of Biomedical Optics Apr 2024Light-sheet fluorescence microscopy (LSFM) has emerged as a powerful and versatile imaging technique renowned for its remarkable features, including high-speed 3D...
SIGNIFICANCE
Light-sheet fluorescence microscopy (LSFM) has emerged as a powerful and versatile imaging technique renowned for its remarkable features, including high-speed 3D tomography, minimal photobleaching, and low phototoxicity. The interference light-sheet fluorescence microscope, with its larger field of view (FOV) and more uniform axial resolution, possesses significant potential for a wide range of applications in biology and medicine.
AIM
The aim of this study is to investigate the interference behavior among multiple light sheets (LSs) in LSFM and optimize the FOV and resolution of the light-sheet fluorescence microscope.
APPROACH
We conducted a detailed investigation of the interference effects among LSs through theoretical derivation and numerical simulations, aiming to find optimal parameters. Subsequently, we constructed a customized system of multi-LSFM that incorporates both interference light sheets (ILS) and noninterference light-sheet configurations. We performed beam imaging and microsphere imaging tests to evaluate the FOV and axial resolution of these systems.
RESULTS
Using our custom-designed light-sheet fluorescence microscope, we captured the intensity distribution profiles of both interference and noninterference light sheets (NILS). Additionally, we conducted imaging tests on microspheres to assess their imaging outcomes. The ILS not only exhibits a larger FOV compared to the NILS but also demonstrates a more uniform axial resolution.
CONCLUSIONS
By effectively modulating the interference among multiple LSs, it is possible to optimize the intensity distribution of the LSs, expand the FOV, and achieve a more uniform axial resolution.
Topics: Microscopy, Fluorescence; Microspheres; Photobleaching
PubMed: 38629030
DOI: 10.1117/1.JBO.29.4.046501