Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy

Byvaltsev, Vadim A.; Bardonova, Liudmila; Onaka, Naomi R; Polkin, Roman A.; Ochkal, Sergey V.; Shepelev, Valerij V.; Aliyev, Marat A.; Потапов, А. А.

doi:10.3389/fonc.2019.00925

Cited by 86 publications

(48 citation statements)

References 53 publications

(79 reference statements)

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“…To identify agents for improving metabolic conditions via enhanced autophagy, we first conducted a screen for autophagy flux enhancers. HeLa cells were treated for 24 h with components of a chemical library comprising 658-natural compounds and then stained with acridine orange (AO) as an indicator of acidic lysosomes 22 – 25 . Discovering small molecules that enhance lysosomal functionality can be an effective strategy for targeting metabolic disorders such as obesity and diabetes, as they act as activators of autophagic-turnover 10 , 26 .…”

Section: Resultsmentioning

confidence: 99%

Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction

et al. 2021

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Disorders of autophagy, a key regulator of cellular homeostasis, cause a number of human diseases. Due to the role of autophagy in metabolic dysregulation, there is a need to identify autophagy regulators as therapeutic targets. To address this need, we conducted an autophagy phenotype-based screen and identified the natural compound kaempferide (Kaem) as an autophagy enhancer. Kaem promoted autophagy through translocation of transcription factor EB (TFEB) without MTOR perturbation, suggesting it is safe for administration. Moreover, Kaem accelerated lipid droplet degradation in a lysosomal activity-dependent manner in vitro and ameliorated metabolic dysregulation in a diet-induced obesity mouse model. To elucidate the mechanism underlying Kaem’s biological activity, the target protein was identified via combined drug affinity responsive target stability and LC–MS/MS analyses. Kaem directly interacted with the mitochondrial elongation factor TUFM, and TUFM absence reversed Kaem-induced autophagy and lipid degradation. Kaem also induced mitochondrial reactive oxygen species (mtROS) to sequentially promote lysosomal Ca2+ efflux, TFEB translocation and autophagy induction, suggesting a role of TUFM in mtROS regulation. Collectively, these results demonstrate that Kaem is a potential therapeutic candidate/chemical tool for treating metabolic dysregulation and reveal a role for TUFM in autophagy for metabolic regulation with lipid overload.

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Section: Resultsmentioning

confidence: 99%

Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction

et al. 2021

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“…Skin samples were placed on plastic film surrounded by moist gauze for the duration of the experiment. AO (MW: 301.8 Da, excitation wavelength = 500 nm, emission wavelength = 526 nm) (Mavig, Munich, Germany) was used as a contrast agent for EVCM [29]. The stock solution of 10 mg/ml was diluted in phosphate-buffered saline to a concentration of 0.06 mg/ml.…”

Section: Interventionmentioning

confidence: 99%

Electronic Pneumatic Injection‐Assisted Dermal Drug Delivery Visualized by Ex Vivo Confocal Microscopy

et al. 2020

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Background and Objectives: Electronic pneumatic injection (EPI) is a technique for dermal drug delivery, which is increasingly being used in clinical practice. However, only few studies have been reported on cutaneous drug distribution and related clinical endpoints. We aimed to visualize the immediate cutaneous drug distribution, changes in skin architecture, and related clinical endpoint of EPI. Study Design/Materials and Methods: Acridine orange (AO) solution was administered to ex vivo porcine skin by EPI at pressure levels from 4 to 6 bar with a fixed injection volume of 50 µl and nozzle size of 200 µm. Immediate cutaneous distribution was visualized using ex vivo confocal microscopy (EVCM). Changes in skin architecture were visualized using both EVCM and hematoxylin and eosin-stained cryosections. Results: The defined immediate endpoint was a clinically visible papule formation on the skin. The pressure threshold to consistently induce a papule was 4 bar, achieving delivery of AO to the deep dermis (2319 µm axial and 5944 µm lateral distribution). Increasing the pressure level to 6 bar did not lead to significant differences in axial and lateral dispersion (P = 0.842, P = 0.905; respectively). A distinctively hemispherical distribution pattern was identified. Disruption of skin architecture occurred independently of pressure level, and consisted of subepidermal clefts, dermal vacuoles, and fragmented collagen. Conclusions: This is the first study to relate a reproducible clinical endpoint to EPI-assisted immediate drug delivery using EVCM. An EPI-induced skin papule indicates dermal drug delivery throughout all layers of the dermis, independent of pressure level settings. Lasers Surg. Med.

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“…We chose acridine orange as a dye to visualize hydrolysis since it is a cationic dye and therefore is highly soluble in water and compatible with CMC 35 . Additionally, it enables the incorporation of microorganisms into the system since its toxicity is limited 36 .…”

Section: Resultsmentioning

confidence: 99%

Developing a method for real-time visualization of cellulase activity

Kumari

Sayas

Bucki

et al. 2020

Preprint

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AbstractStudying the interactions between microorganisms and plant roots is crucial for understanding a variety of phenomena concerning crop yield and health. The role of root surface properties in these interactions, is rarely addressed. To this end, we previously built a synthetic system, from the inert polymer polydimethyl siloxane (PDMS), mimicking the root surface microstructure, using a replication technique. This replica enables the study of isolated effects of surface structure on microorganism-plant interactions. Since the root surface is composed mostly of cellulose, using cellulose-like materials as our replica, instead of PDMS, is the next logical step. This will enable following the hydrolysis of such surfaces as a result of microorganisms secreting Plant Cell Wall Degrading Enzymes (PCWDE), and in particular, cellulase. Visualization of such hydrolysis in a synthetic system can assist in studying the localization and activity of microorganisms and how they correlate with surface microtopography, separately from chemical plant signals.In this work, we modified the known carboxymethyl cellulase (CMC) hydrolysis visualization method to enable real-time tracking of cellulase activity of microorganisms on the surface. Surface was formed from pure CMC, rather than CMC incorporated in agar as is often done, and by that, eliminating diffusion issues. Acridine orange dye, which is compatible, at low concentrations, with microorganisms, as opposed to other routinely used dyes, was incorporated into the film. The dye disassociated from the film when hydrolysis occurred, forming a halo surrounding the point of hydrolysis. This enabled real-time visualization since the common need for post hydrolysis dyeing was negated. Using Root Knot Nematode (RKN) as a model organism that penetrates the plant root, we showed it was possible to follow microorganism cellulase secretion on the surface in the form of CMC film hydrolysis. Furthermore, the addition of natural additives, in the form of root extract was also shown to be an option and resulted in an increased RKN response. We tested our newly developed method by changing temperature and pH conditions and by characterization of the hydrolyzed surface using both Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM).This method will be implemented in the future on a root surface microstructure replica. We believe the combination of this new method with our previously developed root surface microstructure replication technique can open a new avenue of research in the field of plant root-microorganism interactions.

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Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy

Cited by 86 publications

References 53 publications

Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction

Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction

Electronic Pneumatic Injection‐Assisted Dermal Drug Delivery Visualized by Ex Vivo Confocal Microscopy

Developing a method for real-time visualization of cellulase activity

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