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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 -
Frontiers in Oncology 2023Traditional external light-based Photodynamic Therapy (PDT)'s application is limited to the surface and minimal thickness tumors because of the inefficiency of light in...
Traditional external light-based Photodynamic Therapy (PDT)'s application is limited to the surface and minimal thickness tumors because of the inefficiency of light in penetrating deep-seated tumors. To address this, the emerging field of radiation-activated PDT (radioPDT) uses X-rays to trigger photosensitizer-containing nanoparticles (NPs). A key consideration in radioPDT is the energy transfer efficiency from X-rays to the photosensitizer for ultimately generating the phototoxic reactive oxygen species (ROS). In this study, we developed a new variant of pegylated poly-lactic-co-glycolic (PEG-PLGA) encapsulated nanoscintillators (NSCs) along with a new, highly efficient ruthenium-based photosensitizer (Ru/radioPDT). Characterization of this NP via transmission electron microscopy, dynamic light scattering, UV-Vis spectroscopy, and inductively coupled plasma mass-spectroscopy showed an NP size of 120 nm, polydispersity index (PDI) of less than 0.25, high NSCs loading efficiency over 90% and accumulation within the cytosolic structure of endoplasmic reticulum and lysosome. The therapeutic efficacy of Ru/radioPDT was determined using PC3 cell viability and clonogenic assays. Ru/radioPDT exhibited minimal cell toxicity until activated by radiation to induce significant cancer cell kill over radiation alone. Compared to protoporphyrin IX-mediated radioPDT (PPIX/radioPDT), Ru/radioPDT showed higher capacity for singlet oxygen generation, maintaining a comparable cytotoxic effect on PC3 cells.
PubMed: 37700826
DOI: 10.3389/fonc.2023.1244709 -
Advanced Science (Weinheim,... May 2024High-resolution spatio-temporal monitoring of the cell membrane lipid order provides visual insights into the complex and sophisticated systems that control cellular...
High-resolution spatio-temporal monitoring of the cell membrane lipid order provides visual insights into the complex and sophisticated systems that control cellular physiological functions. Solvatochromic fluorescent probes are highly promising noninvasive visualization tools for identifying the ordering of the microenvironment of plasma membrane microdomains. However, conventional probes, although capable of structural analysis, lack the necessary long-term photostability required for live imaging at the cellular level. Here, an ultra-high-light-resistant solvatochromic fluorescence probe, 2-N,N-diethylamino-7-(4-methoxycarbonylphenyl)-9,9-dimethylfluorene (FπCM) is reported, which enables live lipid order imaging of cell division. This probe and its derivatives exhibit sufficient fluorescence wavelengths, brightness, polarity responsiveness, low phototoxicity, and remarkable photostability under physiological conditions compared to conventional solvatochromic probes. Therefore, these probes have the potential to overcome the limitations of fluorescence microscopy, particularly those associated with photobleaching. FπCM probes can serve as valuable tools for elucidating mechanisms of cellular processes at the bio-membrane level.
Topics: Fluorescent Dyes; Humans; Microscopy, Fluorescence; Optical Imaging; Cell Membrane
PubMed: 38468355
DOI: 10.1002/advs.202309721 -
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 -
Pharmaceutics Aug 2023Melanoma remains a major public health concern that is highly resistant to standard therapeutic approaches. Photodynamic therapy (PDT) is an underutilised cancer therapy...
Melanoma remains a major public health concern that is highly resistant to standard therapeutic approaches. Photodynamic therapy (PDT) is an underutilised cancer therapy with an increased potency and negligible side effects, and it is non-invasive compared to traditional treatment modalities. Three-dimensional multicellular tumour spheroids (MCTS) closely resemble in vivo avascular tumour features, allowing for the more efficient and precise screening of novel anticancer agents with various treatment combinations. In this study, we utilised A375 human melanoma spheroids to screen the phototoxic effect of zinc phthalocyanine tetrasulfonate (ZnPcS) conjugated to gold nanoparticles (AuNP). The nanoconjugate was synthesised and characterised using ultraviolet-visible spectroscopy, a high-resolution transmission electron microscope (TEM), dynamic light scattering (DLS), and zeta potential (ZP). The phototoxicity of the nanoconjugate was tested on the A375 MCTS using PDT at a fluency of 10 J/cm. After 24 h, the cellular responses were evaluated via microscopy, an MTT viability assay, an ATP luminescence assay, and cell death induction using annexin propidium iodide. The MTT viability assay demonstrated that the photoactivated ZnPcS, at a concentration of 12.73 µM, caused an approximately 50% reduction in the cell viability of the spheroids. When conjugated to AuNPs, the latter significantly increased the cellular uptake and cytotoxicity in the melanoma spheroids via the induction of apoptosis. This novel Zinc Phthalocyanine Nanoconjugate shows promise as a more effective PDT treatment modality.
PubMed: 37765232
DOI: 10.3390/pharmaceutics15092264 -
Materials Today. Bio Aug 2023Development of lysosomes and mitochondria dual-targeting photosensitizer with the virtues of near-infrared (NIR) emission, highly efficient reactive oxygen generation,...
Development of lysosomes and mitochondria dual-targeting photosensitizer with the virtues of near-infrared (NIR) emission, highly efficient reactive oxygen generation, good phototoxicity and biocompatibility is highly desirable in the field of imaging-guided photodynamic therapy (PDT) for cancer. Herein, a new positively charged amphiphilic organic compound (2-(2-(5-(7-(4-(diphenylamino)phenyl)benzo[][1,2,5]thiadiazol-4-yl)thiophen-2-yl)vinyl)-3-methylbenzo[]thiazol-3-ium iodide) () based on a D-A--A structure is designed and comprehensively investigated. demonstrates special lysosomes and mitochondria dual-organelles targeting, bright NIR aggregation-induced emission (AIE) at 736 nm, high singlet oxygen (O) quantum yield (0.442), as well as good biocompatibility and photostability. In addition, can act as a two-photon imaging agent for the elaborate observation of living cells and blood vessel networks of tissues. Upon light irradiation, obvious decrease of mitochondrial membrane potential (MMP), abnormal mitochondria morphology, as well as phagocytotic vesicles and lysosomal disruption in cells are observed, which further induce cell apoptosis and resulting in enhanced antitumor activity for cancer treatment. experiments reveal that can inhibit tumor growth efficiently upon light exposure. These findings demonstrate that this dual-organelles targeted has great potential for clinical imaging-guided photodynamic therapy, and this work provides a new avenue for the development of multi-organelles targeted photosensitizers for highly efficient cancer treatment.
PubMed: 37502829
DOI: 10.1016/j.mtbio.2023.100721 -
Journal of Clinical Medicine Oct 2023Thiopurines are an effective treatment for the maintenance of remission in inflammatory bowel disease (IBD). They can present adverse effects (AEs), with myelotoxicity...
Incidence of Myelotoxicity and Other Adverse Effects Related to Thiopurine Starting in Patients with Inflammatory Bowel Disease: Retrospective Observational Study in a Third-Level Hospital.
BACKGROUND AND OBJECTIVES
Thiopurines are an effective treatment for the maintenance of remission in inflammatory bowel disease (IBD). They can present adverse effects (AEs), with myelotoxicity being the most relevant. This study aims to determine the incidence of AEs related to the starting of thiopurines in our centre.
METHODOLOGY
Retrospective study. The AEs in patients that were started on thiopurines between January 2016 and June 2020 were registered, with a two-year follow-up. The mean and standard deviation were used to describe the quantitative variables, and percentages and confidence intervals were used for the qualitative variables. The statistical significance was set at a -value < 0.05.
RESULTS
98 patients were included, with 64 AEs detected in 48 patients (49%). Most of the AEs appeared in the first 6 months. The most relevant were: 21 neutropenia (21.4%), 19 hypertransaminasemia (19.4%), 13 digestive intolerances (13.2%), 6 acute pancreatitis (6.12%), 3 phototoxicity (3%), and 2 unknown origin fevers (2%). In 29 patients (29.4%) the treatment had to be suspended due to AEs. In 11 cases (11.2%), azathioprine (AZA) was switched to 6-mercaptopurine (6 MP) as 5 showed tolerance and 6 patients needed suspension due to AEs. Eight patients required hospital admission, but none of them needed intensive care unit admission. There were no fatal adverse effects.
CONCLUSIONS
Thiopurines are a safe drug with few AEs, especially after the first months of treatment. These results suggest that periodic analytic follow-up may not be necessary after the initial period of treatment.
PubMed: 37892708
DOI: 10.3390/jcm12206571 -
Cureus Mar 2024Introduction Skin photoaging is caused by prolonged exposure to sunlight, particularly ultraviolet rays (UV). High cumulative levels of UV radiation may cause burning,...
Introduction Skin photoaging is caused by prolonged exposure to sunlight, particularly ultraviolet rays (UV). High cumulative levels of UV radiation may cause burning, photoallergic or phototoxic reactions, pigmentary changes, photoaging, and even immunosuppression and skin cancers. Therefore, this study aims to assess knowledge, attitude, reception, and preventive practices towards skin photoaging among the Jazan general population in Saudi Arabia and its determinants. Methods A descriptive cross-sectional study was conducted among the general population of Jazan, Saudi Arabia, who were aged 18 years and above and agreed to participate in the study. The calculated minimum sample size was 385. An online, semi-structured, self-administered questionnaire was distributed conveniently in Google Forms through social media platforms. It included four sections: The first section was about sociodemographic characteristics. The second section assessed the smoking, exercise, and healthy diet behavior of participants and the use of sunscreen. The third section assessed the knowledge regarding the photoaging process and its preventive measures utilization using three-point Likert scale questions. The fourth section assessed attitudes towards the photoaging process and its preventive measures through three-point Likert scales. Results The study included 452, of which 243 (53.76%) were aged 18-30 years, 258 (57.08%) were females, and 272 (60.18%) had white skin color. Approximately 417 (92.26%) were nonsmokers. Sixty-eight percent (372) spent 1-3 hours in the sun. Social media was the primary source of information on photoaging 81 (17.92%). Around 234 (51.77%) defined photoaging correctly. Regarding sunscreen usage, 58 (12.83%) always use sunscreen, and 177 (39.16%) never use it. However, 191 (42.26%) recognized the correct sunscreen application. Approximately 233 (51.5%) and 240 (53.1%) of respondents had fair knowledge and a positive attitude regarding photoaging and sunscreen use. Being female, pursuing university and postgraduate education, and taking information on photoaging from a physician were linked to a higher knowledge of photoaging (p<0.05). Participants who never use sunscreen had lower knowledge than those who always use it (p<0.001). None of the demographic factors was associated with the attitude towards sunscreen use (p>0.05). Conclusion There is a substantial gap in knowledge and preventive practices related to skin photoaging among the Jazan general population in Saudi Arabia. Gender, education level, and information sources influence knowledge levels. Targeted educational interventions are needed to enhance awareness and promote healthier practices, particularly sun exposure and photoaging prevention.
PubMed: 38586780
DOI: 10.7759/cureus.55710 -
Frontiers in Oral Health 2024Chronic periodontitis is a ubiquitous inflammatory disease in dental healthcare that is challenging to treat due to its impact on bone and tooth loss. Conventional... (Review)
Review
Chronic periodontitis is a ubiquitous inflammatory disease in dental healthcare that is challenging to treat due to its impact on bone and tooth loss. Conventional mechanical debridement has been challenging in eliminating complex subgingival biofilms. Hence, adjunctive approaches like low-level laser antimicrobial photodynamic therapy (A-PDT) utilising methylene blue (MB) have been emerging approaches in recent times. This review evaluates the latest research on the use of MB-mediated A-PDT to decrease microbial count and enhance clinical results in chronic periodontitis. Studies have shown the interaction between laser light and MB generates a phototoxic effect thereby, eliminating pathogenic bacteria within periodontal pockets. Moreover, numerous clinical trials have shown that A-PDT using MB can reduce probing depths, improve clinical attachment levels, and decrease bleeding during probing in comparison to traditional treatment approaches. Notably, A-PDT shows superior antibiotic resistance compared to conventional antibiotic treatments. In conclusion, the A-PDT using MB shows promise as an adjunctive treatment for chronic periodontitis. Additional research is required to standardize treatment protocols and assess long-term outcomes of A-PDT with MB in the treatment of periodontitis.
PubMed: 38872983
DOI: 10.3389/froh.2024.1407201 -
Clinical Ophthalmology (Auckland, N.Z.) 2023Diabetes is associated with ocular complications including diabetic macular edema (DME). Current therapies are invasive and include repeated intravitreal injections and...
PURPOSE
Diabetes is associated with ocular complications including diabetic macular edema (DME). Current therapies are invasive and include repeated intravitreal injections and laser therapy. Photobiomodulation (PBM) is a treatment (Tx) that utilizes selected wavelengths of light to induce cellular benefits including reduction of inflammation and edema. This single-center, open-label, post-hoc analysis explored the utility of multiwavelength PBM in subjects with DME.
METHODS
Analysis included review of data from patients undergoing standard clinical care with an approved and marketed PBM medical device, the Valeda Light Delivery System. Subjects with early-stage DME with good vision (Best-corrected visual acuity (BCVA) > 20/25, logMAR > 0.1) were evaluated in clinic and treated with one series of multiwavelength PBM (Tx delivered 3x/week over 3-4 weeks; total of 9 Tx sessions). Clinical, anatomical, and safety parameters were assessed in addition to subjective quality of life.
RESULTS
A total of 30 eyes (19 subjects) were analyzed. Subjects were predominately male (68.4%) with a mean age of 56 ± 14 years. Reductions in central retinal thickness (CRT), resolution of intraretinal fluid (IRF) and improvement in diabetic retinopathy severity scale scores were observed following PBM treatment in select patients. Baseline BCVA remained stable over the follow-up observation period of 3 months post-PBM. Approximately 64% of patients reported subjective improvements in their ocular condition and decreased influence in everyday life. Detailed OCT evaluations confirmed no safety issues related to phototoxicity up to 16 months.
CONCLUSION
Early-stage DME subjects treated with Valeda multiwavelength PBM showed improvements in clinical and anatomical parameters. The Valeda multiwavelength PBM approach demonstrates a favorable safety profile with no signs of phototoxicity following an independent OCT review. PBM therapy may offer an alternative, non-invasive treatment strategy with a unique mechanism and modality for patients with early-stage DME.
PubMed: 38026594
DOI: 10.2147/OPTH.S415883