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Journal of Photochemistry and... Jul 2024With the rapid development of nanotechnology, various functional nanomaterials have shown exciting potential in biomedical areas such as drug delivery, antitumor, and...
Evaluation of 1,9-Dimethyl-Methylene Blue nanoencapsulation using rhamnolipid nanoparticles to potentiate the Photodynamic Therapy technique in Candida albicans: In vitro study.
With the rapid development of nanotechnology, various functional nanomaterials have shown exciting potential in biomedical areas such as drug delivery, antitumor, and antibacterial therapy. These nanomaterials improve the stability and selectivity of loaded drugs, reduce drug-induced side effects, realize controlled and targeted drug release, and increase therapeutic efficacy. The increased resistance to antifungal microbicides in medical practice and their side effects stimulate interest in new therapies, such as Photodynamic Therapy (PDT), which do not generate resistance in microorganisms and effectively control the pathology. The present study aimed to evaluate, in vitro, the efficacy of photodynamic therapy on Candida albicans using 1,9-Dimethyl-Methylene Blue (DMMB) as photosensitizer, red LED (λ630), and nanoencapsulation of DMMB (RL-NPs/DMMB) using rhamnolipids produced by Pseudomonas aeruginosa to evaluate if there is better performance of DMMB + RL particles compared to DMMB alone via the characterization of DMMB + RL and colony forming count. The tests were carried out across six experimental groups (Control, DMMB, RL-NPs, RL-NPs/DMMB, PDT and PDT + RL-NPs/DMMB) using in the groups with nanoparticles, DMMB (750 ng/mL) encapsulated with rhamnolipids in a 1:1 ratio, the light source consisted of a prototype built with a set of red LEDs with an energy density of 20 J/cm. The results showed that applying PDT combined with encapsulation (RL-NPs/DMMB) was a more practical approach to inhibit Candida albicans (2 log reduction) than conventional applications, with a possible clinical application protocol.
Topics: Candida albicans; Photochemotherapy; Glycolipids; Methylene Blue; Photosensitizing Agents; Nanoparticles; Pseudomonas aeruginosa; Antifungal Agents; Drug Compounding
PubMed: 38788534
DOI: 10.1016/j.jphotobiol.2024.112943 -
Bioorganic Chemistry Jul 2024Ferroptosis is a novel style of cell death, and studies have shown that ferroptosis is strongly associated with spinal cord injury (SCI). A large number of ferroptosis...
Ferroptosis is a novel style of cell death, and studies have shown that ferroptosis is strongly associated with spinal cord injury (SCI). A large number of ferroptosis inhibitors have been reported, but so far no ferroptosis inhibitor has been used clinically. Therefore there is an urgent need to discover a better inhibitor of ferroptosis. In this study, 24 novel sulfonamide phenothiazine ferroptosis inhibitors were designed and synthesized, followed by structure-activity relationship studies on these compounds. Among them, compound 23b exhibited the best activity in Erastin-induced PC12 cells (EC = 0.001 μM) and demonstrated a low hERG inhibition activity (IC > 30 μM). Additionally, compound 23b was identified as a ROS scavenger and showed promising therapeutic effects in an SD rat model of SCI. Importantly, 23b did not display significant toxicity in both in vivo and in vitro experiments and show good pharmacokinetic properties. These findings suggest that compound 23b, a novel ferroptosis inhibitor, holds potential as a therapeutic agent for spinal cord injury and warrants further investigation.
Topics: Animals; Spinal Cord Injuries; Rats; Structure-Activity Relationship; Ferroptosis; Drug Design; Phenothiazines; Sulfonamides; PC12 Cells; Molecular Structure; Rats, Sprague-Dawley; Dose-Response Relationship, Drug; Humans; Male
PubMed: 38788362
DOI: 10.1016/j.bioorg.2024.107458 -
Journal of Biomedical Optics May 2024Fiber-optic microendoscopy is a promising approach to noninvasively visualize epithelial nuclear morphometry for early cancer and precancer detection. However, the...
SIGNIFICANCE
Fiber-optic microendoscopy is a promising approach to noninvasively visualize epithelial nuclear morphometry for early cancer and precancer detection. However, the broader clinical application of this approach is limited by a lack of topical contrast agents available for use.
AIM
The aim of this study was to evaluate the ability to image nuclear morphometry with a novel fiber-optic microendoscope used together with topical application of methylene blue (MB), a dye with FDA approval for use in chromoendoscopy in the gastrointestinal tract.
APPROACH
The low-cost, high-resolution microendoscope implements scanning darkfield imaging without complex optomechanical components by leveraging programmable illumination and the rolling shutter of the image sensor. We validate the integration of our system and MB staining for visualizing epithelial cell nuclei by performing imaging on fresh animal specimens and imaging on healthy volunteers.
RESULTS
The results indicate that scanning darkfield imaging significantly reduces specular reflection and resolves epithelial nuclei with enhanced image contrast and spatial resolution compared to non-scanning widefield imaging. The image quality of darkfield images with MB staining is comparable to that of fluorescence images with proflavine staining.
CONCLUSIONS
Our approach enables real-time microscopic evaluation of nuclear patterns and has the potential to be a powerful noninvasive tool for early cancer detection.
Topics: Methylene Blue; Animals; Humans; Cell Nucleus; Fiber Optic Technology; Equipment Design; Endoscopy; Administration, Topical
PubMed: 38774711
DOI: 10.1117/1.JBO.29.5.050501 -
Molecular Pain 2024Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of...
Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of MB leading to cutaneous toxicity has been reported. In this study, we sought to characterize MB-induced cutaneous toxicity and investigate the underlying mechanisms. To induce MB-induced cutaneous toxicity, we injected 64 adult male Sprague-Dawley rates with 200 µL saline (vehicle) or 1%, 0.1%, or 0.01% MB in the plantar hind paws. Paw swelling, skin histologic changes, and heat and mechanical hyperalgesia were measured. Injection of 1%, but not 0.1% or 0.01% MB, produced significant paw swelling compared to saline. Injection of 1% MB produced heat hyperalgesia but not mechanical hyperalgesia. Pain behaviors were unchanged following injections of 0.1% or 0.01% MB. Global transcriptomic analysis by RNAseq identified 117 differentially expressed genes (111 upregulated, 6 downregulated). Ingenuity Pathway Analysis showed an increased quantity of leukocytes, increased lipids, and decreased apoptosis of myeloid cells and phagocytes with activation of IL-1β and Fos as the two major regulatory hubs. qPCR showed a 16-fold increase in IL-6 mRNA. Thus, using a novel rat model of MB-induced cutaneous toxicity, we show that infiltration of 1% MB into cutaneous tissue causes a dose-dependent pro-inflammatory response, highlighting potential roles of IL-6, IL-1β, and Fos. Thus, anesthesiologists should administer dilute MB intravenously through peripheral venous catheters. Higher concentrations of MB (1%) should be administered through a central venous catheter to minimize the risk of cutaneous toxicity.
Topics: Animals; Male; Rats, Sprague-Dawley; Methylene Blue; Hyperalgesia; Inflammation; Disease Models, Animal; Skin; Dose-Response Relationship, Drug; Hot Temperature; Rats; Interleukin-1beta
PubMed: 38773702
DOI: 10.1177/17448069241259535 -
The Journal of Organic Chemistry Jun 2024Here, a novel iodine-catalyzed direct cyclization of -nitrothiophenols with cyclohexanones to phenothiazines has been described without external oxidants and hydrogen...
Here, a novel iodine-catalyzed direct cyclization of -nitrothiophenols with cyclohexanones to phenothiazines has been described without external oxidants and hydrogen acceptors. The nitro of -nitrothiophenol works as both a hydrogen acceptor and a coupling group, and water is the only byproduct. The reaction involves the reduction of nitro groups, C-H bond thioetherification, and C-H bond dehydroaromatization. This scheme offers broad synthetic value for further elaborations, as exemplified by a 3-step total synthesis of antipsychotic chlorpromazine.
PubMed: 38773694
DOI: 10.1021/acs.joc.4c00039 -
Scientific Reports May 2024The present investigation explores the efficacy of green algae Ulva lactuca biochar-sulfur (GABS) modified with HSO and NaHCO in adsorbing methylene blue (MB) dye from...
The present investigation explores the efficacy of green algae Ulva lactuca biochar-sulfur (GABS) modified with HSO and NaHCO in adsorbing methylene blue (MB) dye from aqueous solutions. The impact of solution pH, contact duration, GABS dosage, and initial MB dye concentration on the adsorption process are all methodically investigated in this work. To obtain a thorough understanding of the adsorption dynamics, the study makes use of several kinetic models, including pseudo-first order and pseudo-second order models, in addition to isotherm models like Langmuir, Freundlich, Tempkin, and Dubinin-Radushkevich. The findings of the study reveal that the adsorption capacity at equilibrium (q) reaches 303.78 mg/g for a GABS dose of 0.5 g/L and an initial MB dye concentration of 200 mg/L. Notably, the Langmuir isotherm model consistently fits the experimental data across different GABS doses, suggesting homogeneous adsorption onto a monolayer surface. The potential of GABS as an efficient adsorbent for the extraction of MB dye from aqueous solutions is highlighted by this discovery. The study's use of kinetic and isotherm models provides a robust framework for understanding the intricacies of MB adsorption onto GABS. By elucidating the impact of various variables on the adsorption process, the research contributes valuable insights that can inform the design of efficient wastewater treatment solutions. The comprehensive analysis presented in this study serves as a solid foundation for further research and development in the field of adsorption-based water treatment technologies.
Topics: Methylene Blue; Charcoal; Ulva; Adsorption; Water Pollutants, Chemical; Kinetics; Water Purification; Sulfur; Hydrogen-Ion Concentration; Water; Edible Seaweeds
PubMed: 38773106
DOI: 10.1038/s41598-024-61868-9 -
Veterinary Anaesthesia and Analgesia 2024To compare changes in oesophageal (T-Oeso) and rectal (T-Rec) temperature in dogs during general anaesthesia and premedicated with fentanyl, medetomidine-fentanyl or...
OBJECTIVE
To compare changes in oesophageal (T-Oeso) and rectal (T-Rec) temperature in dogs during general anaesthesia and premedicated with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl.
STUDY DESIGN
Prospective, randomized, blind clinical study.
ANIMALS
A total of 120 healthy dogs, aged 2-10 years and weighing 5-20 kg.
METHODS
Dogs were randomly allocated to one of three groups. Animals of F group were premedicated with fentanyl (0.01 mg kg), MF group with medetomidine (0.005 mg kg) and fentanyl (0.01 mg kg) and AF group with acepromazine (0.01 mg kg) and fentanyl (0.01 mg kg). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen-air mixture. Fentanyl was administered continuously (0.01 mg kg hour). The T-Oeso, T-Rec and ambient temperatures were recorded after induction (T0) and subsequently at 10 minute intervals for 60 minutes (T10-T60). Data were analysed using anova or their non-parametric equivalents (p < 0.05).
RESULTS
Median T-Oeso was significantly higher in MF group between T0-T20 compared with other groups. Median T-Oeso significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T30), 37.1 °C (T40), 36.9 °C (T50) and 36.6 °C (T60), in MF group from 38.3 °C (T0) to 37.7 °C (T30), 37.5 °C (T40), 37.2 °C (T50) and 37.1 °C (T60) and in AF group from 37.7 °C (T0) to 37.3 °C (T40), 37.2 °C (T50) and 37.1 °C (T60). The T-Rec significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T40), 37.2 °C (T50) and 36.9 °C (T60), in MF group from 38.3 °C (T0) to 37.5 °C (T50) and 37.4 °C (T60) and in AF group from 38.2 °C (T0) to 37.6 °C (T40), 37.5 °C (T50) and 37.4 °C (T60).
CONCLUSIONS AND CLINICAL RELEVANCE
Premedication with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl in the doses used decreased the T-Oeso and T-Rec. The T-Oeso at the beginning of anaesthesia was higher after premedication with medetomidine-fentanyl. However, this difference was not clinically significant.
Topics: Animals; Dogs; Fentanyl; Medetomidine; Acepromazine; Male; Female; Body Temperature; Esophagus; Rectum; Prospective Studies; Anesthesia, General; Anesthetics, Intravenous; Anesthetics, Combined; Preanesthetic Medication
PubMed: 38772852
DOI: 10.1016/j.vaa.2024.04.003 -
Lasers in Medical Science May 2024Tooth discoloration is a common concern in antimicrobial photodynamic therapy (aPDT) using various photosensitizers (PS). Toluidine Blue (TB), Methylene Blue (MB),...
BACKGROUND
Tooth discoloration is a common concern in antimicrobial photodynamic therapy (aPDT) using various photosensitizers (PS). Toluidine Blue (TB), Methylene Blue (MB), Phthalocyanine (Pc), and 2-mercaptopyridine-substituted zinc phthalocyanine (TM-ZnPc) are among those studied, but their relative impacts on tooth discoloration remain unclear.
AIM
This study aimed to compare the effects of TB, MB, Pc, and TM-ZnPc in aPDT on tooth discoloration, utilizing a controlled experimental setup.
MATERIALS AND METHODS
The study comprised seventy-five single-rooted incisors with root canals. Following meticulous preparation, a standardized area on the crown surface was designated for examination, and precise measurements of the initial tooth colors were recorded. Samples were randomly divided into five groups: Negative control, MB, TM, Pc, and TM-ZnPc. Photoactivation was performed using LED light, and color measurements were taken at multiple time points up to 90 days. Data were converted to Lab* color values of the CIE Lab* color system (International Commission on Illumination, Vienna, Austria), and ΔE values were calculated. Statistical analysis was performed using Two-way ANOVA and Post-Hoc Tukey tests (p < 0.05).
RESULTS
At day 7 and 30, TM-ZnPc and Pc caused less discoloration compared to MB and TB. TM-ZnPc caused more tooth discoloration compared to Pc (p < 0.05). Compared to baseline, MB and TM-ZnPc caused more tooth discoloration at 30 days and TB caused more tooth discoloration at 90 days (p < 0.05). No significant difference was observed in terms of tooth discoloration at all periods evaluated after Pc application (p > 0.05). All photosensitizers tested in the study caused tooth coloration.
CONCLUSION
All PS induced clinically detectable tooth discoloration, with TB and MB causing more significant discoloration compared to Pc and TM-ZnPc at certain time points. TM-ZnPc and Pc demonstrated more stable coloration levels over time, suggesting their potential reliability in aPDT applications. This study highlights the importance of selecting appropriate PS to minimize tooth discoloration in aPDT, with Pc showing promise in this regard.
Topics: Photochemotherapy; Photosensitizing Agents; Humans; Tooth Discoloration; Tolonium Chloride; Methylene Blue; Spectrophotometry; Isoindoles; Zinc Compounds; Indoles; Organometallic Compounds
PubMed: 38771549
DOI: 10.1007/s10103-024-04085-0 -
The Journal of Physical Chemistry. A May 2024We have designed, synthesized, and characterized a donor-acceptor triad, , that consists of a π-interacting phenothiazine-linked porphyrin as a donor and sensitizer and...
We have designed, synthesized, and characterized a donor-acceptor triad, , that consists of a π-interacting phenothiazine-linked porphyrin as a donor and sensitizer and fullerene as an acceptor to seek charge separation upon photoexcitation. The optical absorption spectrum revealed red-shifted Soret and Q-bands of porphyrin due to charge transfer-type interactions involving the two ethynyl bridges carrying electron-rich and electron-poor substituents. The redox properties suggested that the phenothiazine-porphyrin part of the molecule is easier to oxidize and the fullerene part is easier to reduce. DFT calculations supported the redox properties wherein the electron density of the highest molecular orbital (HOMO) was distributed over the donor phenothiazine-porphyrin entity while the lowest unoccupied molecular orbital (LUMO) was distributed over the fullerene acceptor. TD-DFT studies suggested the involvement of both the S and S states in the charge transfer process. The steady-state emission spectrum, when excited either at porphyrin Soret or visible band absorption maxima, revealed quenched emission both in nonpolar and polar solvents, suggesting the occurrence of excited state events. Finally, femtosecond transient absorption spectral studies were performed to witness the charge separation by utilizing solvents of different polarities. The transient data was further analyzed by GloTarAn by fitting the data with appropriate models to describe photochemical events. From this, the average lifetime of the charge-separated state calculated was found to be 169 ps in benzonitrile, 319 ps in dichlorobenzene, 1.7 ns in toluene for Soret band excitation, and ∼320 ps for Q-band excitation in benzonitrile.
PubMed: 38758579
DOI: 10.1021/acs.jpca.4c00976 -
Central Nervous System Agents in... May 2024Alzheimer's disease is a neurodegenerative disorder that affects learning, memory and behavioral turbulence in elderly patients. Acetylcholinesterase (AChE) inhibitors...
BACKGROUND
Alzheimer's disease is a neurodegenerative disorder that affects learning, memory and behavioral turbulence in elderly patients. Acetylcholinesterase (AChE) inhibitors act as anti-Alzheimer's agents. Phenothiazine derivatives are considered momentous anti-Alzheimer's agents because of their AChE inhibitory activity. The elevated levels and increased expression of this protein have been associated with Alzheimer's disease. Coumarin-fused phenothiazines have emerged as significant anti-Alzheimer's agents due to their notable receptor inhibitory activity.
OBJECTIVE
Some unique phenothiazine analogs were designed, and computational studies were conducted to explore their inhibitory activity against the AChE enzyme (PDB id: 4EY7) by using the Schrodinger suite-2019-4.
METHODS
Docking studies were conducted by using the Glide module; binding free energies were calculated by means of the Prime MM-GBSA module, and Molecular dynamics (MD) simulation was performed by using the Desmond module of the Schrodinger suite. Glide scores were used to find out the binding affinity of the ligands with the target 4EY7.
RESULTS
The compounds exhibited enhanced hydrophobic interactions and formed hydrogen bonds, effectively impeding Acetylcholinesterase. The Glide scores for the compounds ranged from -13.4237 to -8.43439, surpassing the standard (Donepezil) with a score of -16.9898. Interestingly, a positive value was obtained for the MM-GBSA binding of the potent inhibitor. To gain insights into the dynamic behavior of the protein A8, molecular dynamics (MD) simulations were employed.
CONCLUSION
Based on the results, the study concludes that phenothiazine derivatives show promise as acetylcholinesterase inhibitors. Compounds with notable Glide scores are poised to exhibit significant anti-Alzheimer's activity, suggesting their potential therapeutic efficacy. Further in vitro and in vivo investigations are warranted to validate and explore the therapeutic potentials of these compounds.
PubMed: 38757327
DOI: 10.2174/0118715249300784240430110628