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The Journal of Organic Chemistry Nov 2022A mild and efficient method for preparation of 3-sulfenyl and 3-selenyl coumarins and quinolinones mediated by artificial light or sunlight is presented. The elaborated...
A mild and efficient method for preparation of 3-sulfenyl and 3-selenyl coumarins and quinolinones mediated by artificial light or sunlight is presented. The elaborated protocol highlights the use of nonyl acridine orange as a photocatalyst to generate a sulfenyl radical from thiols that is further trapped by a heterocycle. The utility of the protocol is justified by a diverse scope of thiols, including short cysteine-containing peptides. The same reaction conditions can be applied for preparation of 3-selenyl coumarins and quinolinones. Various protected and unprotected selenocysteine-containing peptides were successfully utilized demonstrating high tolerance for amino acids with sensitive groups (Arg, Lys, Trp, His, and Tyr).
Topics: Acridine Orange; Coumarins; Quinolones; Prospective Studies; Peptides; Cysteine
PubMed: 36310352
DOI: 10.1021/acs.joc.2c01803 -
International Journal of Thermophysics 2023In this study, we present a novel method to detect airborne particulates using air-coupled photoacoustics, with a goal toward detecting viral content in respiratory...
In this study, we present a novel method to detect airborne particulates using air-coupled photoacoustics, with a goal toward detecting viral content in respiratory droplets. The peak photoacoustic frequency emitted from micrometer-sized particulates is over 1000 MHz, but at this frequency, the signals are highly attenuated in air. Measurements were taken using a thin planar absorber and ultrasound transducers with peak sensitivity between 50 kHz and 2000 kHz and a 532 nm pulsed laser to determine the optimum detection frequency. 350 kHz to 500 kHz provided the highest amplitude signal while minimizing attenuation in air. To simulate the expulsion of respiratory droplets, an atomizer device was used to spray droplets into open air through a pulsed laser. Droplets were composed of water, water with acridine orange dye, and water with gold nanoparticles. The dye and nanoparticles were chosen due to their similarity in the UV absorption peaks when compared to RNA. Using a 260 nm laser, the average photoacoustic signal from water was the highest, and then the signal decreased with dye or nanoparticles. Increasing absorber concentrations within their respective solutions resulted in a decreasing photoacoustic signal, which is opposite to our expectations. Monte Carlo simulations demonstrated that depending on the droplet dimensions, water droplets focus photons to create a localized fluence elevation. Absorbers within the droplet can inhibit photon travel through the droplet, decreasing the fluence. Photoacoustic signals are created through optical absorption within the droplet, potentially amplified with the localized fluence increase through the droplet focusing effect, with a trade-off in signal amplitude depending on the absorber concentration.
PubMed: 36909209
DOI: 10.1007/s10765-023-03169-3 -
Biomedicines Aug 2022Current multimodal treatment of bone metastases is partially effective and often associated with side effects, and novel therapeutic options are needed. Acridine orange...
Current multimodal treatment of bone metastases is partially effective and often associated with side effects, and novel therapeutic options are needed. Acridine orange is a photosensitizing molecule that accumulates in acidic compartments. After photo- or radiodynamic activation (AO-PDT or AO-RDT), acridine orange can induce lysosomal-mediated cell death, and we explored AO-RDT as an acid-targeted anticancer therapy for bone metastases. We used osteotropic carcinoma cells and human osteoclasts to assess the extracellular acidification and invasiveness of cancer cells, acridine orange uptake and lysosomal pH/stability, and the AO-RDT cytotoxicity in vitro. We then used a xenograft model of bone metastasis to compare AO-RDT to another antiacid therapeutic strategy (omeprazole). Carcinoma cells showed extracellular acidification activity and tumor-derived acidosis enhanced cancer invasiveness. Furthermore, cancer cells accumulated acridine orange more than osteoclasts and were more sensitive to lysosomal death. In vivo, omeprazole did not reduce osteolysis, whereas AO-RDT promoted cancer cell necrosis and inhibited tumor-induced bone resorption, without affecting osteoclasts. In conclusion, AO-RDT was selectively toxic only for carcinoma cells and effective to impair both tumor expansion in bone and tumor-associated osteolysis. We therefore suggest the use of AO-RDT, in combination with the standard antiresorptive therapies, to reduce disease burden in bone metastasis.
PubMed: 36009451
DOI: 10.3390/biomedicines10081904 -
BioMed Research International 2019Musculoskeletal sarcomas are rare and aggressive human malignancies affecting bones and soft tissues with severe consequences, in terms of both morbidity and mortality....
Musculoskeletal sarcomas are rare and aggressive human malignancies affecting bones and soft tissues with severe consequences, in terms of both morbidity and mortality. An innovative technique that combines photodynamic surgery (PDS) and therapy (PDT) with acridine orange has been recently suggested, showing promising results. However, due to the low incidence of sarcoma in humans, this procedure has been attempted only in pilot studies and stronger evidence is needed. Naturally occurring tumors in cats are well-established and advantageous models for human cancers. Feline injection-site sarcoma (FISS) shares with human musculoskeletal sarcomas a mesenchymal origin and an aggressive behavior with a high relapse rate. Furthermore, wide surgical excision is not always possible due to the size and site of development. We assessed the feasibility and the effectiveness of PDS and PDT with acridine orange to prevent FISS recurrence by treating a short case series of cats. For PDS, the surgical field was irrigated with an acridine orange solution and exposed to UV light to enlighten the residual tumor tissue, and the resultant fluorescent areas were trimmed. For PDT, before wound closure, the field was again irrigated with acridine orange solution and exposed to visible light to get the antitumoral cytocidal effect. The procedure was easy to perform and well tolerated, we did not observe any major complications, and all the surgical resection margins were free of disease. Finally, at follow-up, all treated patients did not show evidence of tumor recurrence and had a significantly higher event-free survival rate in respect to a control group treated only by surgery. In conclusion, by this study we demonstrated that, in FISS, PDS and PDT with acridine orange may improve local tumor control, granting a better outcome, and we laid the foundation to validate its effectiveness for the treatment of human musculoskeletal sarcomas.
Topics: Acridine Orange; Animals; Cats; Female; Humans; Male; Muscle Neoplasms; Photochemotherapy; Sarcoma
PubMed: 31360726
DOI: 10.1155/2019/8275935 -
Molecular Neurodegeneration Dec 2022Microglia regulate the response to injury and disease in the brain and spinal cord. In white matter diseases microglia may cause demyelination. However, how microglia...
BACKGROUND
Microglia regulate the response to injury and disease in the brain and spinal cord. In white matter diseases microglia may cause demyelination. However, how microglia respond and regulate demyelination is not fully understood.
METHODS
To understand how microglia respond during demyelination, we fed mice cuprizone-a potent demyelinating agent-and assessed the dynamics of genetically fate-mapped microglia. We then used single-cell RNA sequencing to identify and track the microglial subpopulations that arise during demyelination. To understand how microglia contribute to the clearance of dead oligodendrocytes, we ablated microglia starting at the peak of cuprizone-induced cell death and used the viability dye acridine orange to monitor apoptotic and lytic cell morphologies after microglial ablation. Lastly, we treated serum-free primary microglial cultures to model distinct aspects of cuprizone-induced demyelination and assessed the response.
RESULTS
The cuprizone diet generated a robust microglial response by week 4 of the diet. Single-cell RNA sequencing at this time point revealed the presence of several cuprizone-associated microglia (CAM) clusters. These clusters expressed a transcriptomic signature indicative of cytokine regulation and reactive oxygen species production with altered lysosomal and metabolic changes consistent with ongoing phagocytosis. Using acridine orange to monitor apoptotic and lytic cell death after microglial ablation, we found that microglia preferentially phagocytose lytic carcasses. In culture, microglia exposed to lytic carcasses partially recapitulated the CAM state, suggesting that phagocytosis contributes to this distinct microglial state during cuprizone demyelination.
CONCLUSIONS
Microglia serve multiple roles during demyelination, yet their transcriptomic state resembles other neurodegenerative conditions. The phagocytosis of cellular debris is likely a universal cause for a common neurodegenerative microglial state.
Topics: Animals; Mice; Cuprizone; Microglia; Demyelinating Diseases; Transcriptome; Acridine Orange; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 36514132
DOI: 10.1186/s13024-022-00584-2 -
Chemical Communications (Cambridge,... Nov 2022Molecular de-aggregation was observed at the air/water interface of aqueous microdroplets. We probed this phenomenon using dyes such as Rhodamine 6G (R6G), Rhodamine B,...
Molecular de-aggregation was observed at the air/water interface of aqueous microdroplets. We probed this phenomenon using dyes such as Rhodamine 6G (R6G), Rhodamine B, acridine orange, and fluorescein, which show aggregation-induced shift in fluorescence. The fluorescence micrographs of microdroplets derived from the aqueous solutions of these dyes show that they are monomeric at the air/water interface, but highly aggregated at the core. We propose that rapid evaporation of the solvent influences the de-aggregation of molecules at the air-water interface of the microdroplets.
Topics: Rhodamines; Fluorescein; Acridine Orange; Spectrometry, Fluorescence; Water; Coloring Agents
PubMed: 36250601
DOI: 10.1039/d2cc04587g -
Anatomia, Histologia, Embryologia Jan 2021Significant increases in male infertility and the still unresolved questions on the compatibility and interpretation of current methods in infertility diagnostics call...
Significant increases in male infertility and the still unresolved questions on the compatibility and interpretation of current methods in infertility diagnostics call for new protocols. Morphology, genome damage, RNA content and quantity are currently in practice as the major parameters in evaluation of sperm quality. However, results of various methods are not always in mutual concordance. In this study, in vivo acridine orange (AO) staining, which is presently in application in the estimation of genome damage in reticulocytes, was adjusted for spermatozoa staining. Ten men suffering from oligoasthenoteratozoospermia (OAT) and 10 healthy fertile men were analysed using in vivo AO staining. Microscopic analysis was performed by fluorescent and confocal fluorescent microscopy. Our results show that this method preserves spermatozoa membranes, which enables new insight into spermatozoa genome damage, RNA content in residual cytoplasm, damage of neck area with mitochondrion and tail pathology. The introduced method explains the difference between results of sperm DNA fragmentation assay and the globally used AO staining and opens new options for the development of automated systems. In conclusion, the results of our study offer (a) an innovative approach to the analysis of spermatozoa pathology, (b) enable localization and quantification of RNA in residual cytoplasm, (c) a significant contribution to research of aetiology of infertility in men, (d) open new perspectives for the automatization of sperm quality estimation and (e) improve the personalized approach in the selection of in vitro fertilization protocols.
Topics: Acridine Orange; Humans; Infertility, Male; Male; Microscopy, Fluorescence; RNA; Sperm Motility; Spermatozoa; Staining and Labeling
PubMed: 32840006
DOI: 10.1111/ahe.12606 -
Anticancer Research Jun 2024The increasing incidence of renal cell carcinoma (RCC) and its associated bone metastasis pose challenges in surgical interventions, warranting the exploration of novel...
BACKGROUND/AIM
The increasing incidence of renal cell carcinoma (RCC) and its associated bone metastasis pose challenges in surgical interventions, warranting the exploration of novel therapeutic approaches. Therefore, this study aimed to assess the impact of hematogenously administering acridine orange (AO) alone and in combination with zoledronic acid (ZA) on bone metastasis in RCC.
MATERIALS AND METHODS
RENCA cells (1.0×10 cells/10 μl) were directly injected into the right femur of male BALB/c mice. The mice were categorized into four groups based on the applied therapeutic intervention and were euthanized after five weeks. Micro-computed tomography was performed to quantify the extent of periosteal reaction, indicative of bone metastasis, along the entire length of the femur. Tumor weight and volume were measured at euthanization. Hematoxylin and eosin staining was used to examine the extent of tumor development in the bone. Apoptotic cell, osteoclast, and vascular endothelial growth factor (VEGF)-positive cell counts were assessed using TdT-mediated dUTP-biotin nick end labeling, tartrate-resistant acid phosphatase staining, and VEGF staining, respectively.
RESULTS
The periosteal reaction was significantly reduced in the intervention groups compared to the control group (p<0.05). The apoptotic cell numbers in the intervention groups surpassed that in the control group (p<0.05), whereas those of osteoclasts and VEGF-positive cells in the intervention groups were lower than those in the control group (p<0.05).
CONCLUSION
AO hinders bone metastasis progression in RCC, and combination therapy with ZA may be more effective than AO administration alone.
Topics: Zoledronic Acid; Animals; Carcinoma, Renal Cell; Bone Neoplasms; Kidney Neoplasms; Male; Acridine Orange; Mice; Mice, Inbred BALB C; Apoptosis; Cell Line, Tumor; Humans; Vascular Endothelial Growth Factor A; Imidazoles; X-Ray Microtomography; Xenograft Model Antitumor Assays
PubMed: 38821618
DOI: 10.21873/anticanres.17055 -
Cryo Letters 2021Unsuccessful rooster fertility following cryopreservation may be linked to specific changes in spermatozoa quality, which can be determined using various methods. These... (Review)
Review
Unsuccessful rooster fertility following cryopreservation may be linked to specific changes in spermatozoa quality, which can be determined using various methods. These determinations also facilitate the design of improved freezing and thawing processes. Here, we update the current state of methodologies available for the assessment of rooster semen quality after cryopreservation. Computer-assisted sperm analyses (CASA) is one of the main systems used to analyse motion parameters of spermatozoa (total motility, progressive motility and motion parameters). Moreover, fluorescent techniques and flow cytometry can improve the assessment of various aspects of semen quality (viability, acrosome status, mitochondrial potential, lipid peroxidation, DNA damage, lipid peroxidation and cell debris removal) using specific fluorescent markers such as ethidium bromide, Yo-Pro-1, Annexin V, propidium iodide, SYBR-14, PNA, JC-1, BODIPY, acridine orange and DRAQ5. Transmission electron microscopy also yields valuable information on spermatozoa ultrastructure. The application of these techniques to rooster spermatozoa is reviewed in relation to specific freezing techniques, the effects of cryoprotective agents (CPAs) and extenders, and the determination of spermatozoa quality after cryopreservation.
Topics: Animals; Chickens; Cryopreservation; Cryoprotective Agents; Male; Semen Analysis; Semen Preservation; Sperm Motility; Spermatozoa
PubMed: 33970981
DOI: No ID Found -
Nanomedicine (London, England) Dec 2021To develop a tumor-targeted chemo-photothermal nanomedicine through the functionalization of acridine orange (AO)-loaded gold-core mesoporous silica shell...
To develop a tumor-targeted chemo-photothermal nanomedicine through the functionalization of acridine orange (AO)-loaded gold-core mesoporous silica shell (AuMSS) nanorods with polyethylenimine (PEI) and hyaluronic acid (HA). Functionalization of the AuMSS nanorods was achieved through the chemical linkage of PEI followed by electrostatic adsorption of HA. HA functionalization improved AuMSS' cytocompatibility by decreasing blood hemolysis, and PEI-HA inclusion promoted a controlled and sustained AO release. assays revealed that HA functionalization increased the internalization of nanoparticles by human negroid cervix epithelioid carcinoma cancer (HeLa) cells, and the combinatorial treatment mediated by AuMSS/PEI/HA_AO nanorods presented an enhanced effect, with >95% of cellular death. AuMSS/PEI/HA_AO formulations can act as tumor-targeted chemo-photothermal nanomedicines for the combinatorial therapy of cervical cancer.
Topics: Acridine Orange; Doxorubicin; Gold; Humans; Hyaluronic Acid; Nanoparticles; Nanotubes; Neoplasms; Polyethyleneimine; Silicon Dioxide
PubMed: 34854343
DOI: 10.2217/nnm-2021-0270