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Cell Death & Disease Jun 2024The repurposing of medications developed for central nervous system (CNS) disorders, possessing favorable safety profiles and blood-brain barrier permeability,...
The repurposing of medications developed for central nervous system (CNS) disorders, possessing favorable safety profiles and blood-brain barrier permeability, represents a promising strategy for identifying new therapies to combat glioblastoma (GBM). In this study, we investigated the anti-GBM activity of specific antipsychotics and antidepressants in vitro and in vivo. Our results demonstrate that these compounds share a common mechanism of action in GBM, disrupting lysosomal function and subsequently inducing lysosomal membrane rupture and cell death. Notably, PTEN intact GBMs possess an increased sensitivity to these compounds. The inhibition of lysosomal function synergized with inhibitors targeting the EGFR-PI3K-Akt pathway, leading to an energetic and antioxidant collapse. These findings provide a foundation for the potential clinical application of CNS drugs in GBM treatment. Additionally, this work offers critical insights into the mechanisms and determinants of cytotoxicity for drugs currently undergoing clinical trials as repurposing agents for various cancers, including Fluoxetine, Sertraline, Thioridazine, Chlorpromazine, and Fluphenazine.
Topics: Humans; Glioblastoma; PTEN Phosphohydrolase; Lysosomes; Signal Transduction; Antipsychotic Agents; Animals; Cell Line, Tumor; Mice; Brain Neoplasms; Proto-Oncogene Proteins c-akt; Mice, Nude; Drug Repositioning; Phosphatidylinositol 3-Kinases; ErbB Receptors; Chlorpromazine
PubMed: 38871731
DOI: 10.1038/s41419-024-06779-3 -
Spectrochimica Acta. Part A, Molecular... Jun 2024Scientific studies have demonstrated that conjugates of anticancer drugs with metal nanoparticles (MeNPs) lead to a more effective deactivation of tumor cells compared...
Scientific studies have demonstrated that conjugates of anticancer drugs with metal nanoparticles (MeNPs) lead to a more effective deactivation of tumor cells compared to free drugs. Similarly, it has been established that conjugates of antibiotics with MeNPs exhibit higher biocidal activity against bacteria than their unbound counterparts. However, limited information is available regarding conjugates formed from drugs other than anticancer and antibiotics. Therefore, our research aims to develop synthesis methods for conjugates of chlorpromazine (CPZ), a neuroleptic, with gold nanoparticles (AuNPs). CPZ-AuNP conjugates were prepared through a ligand exchange reaction conducted on the surface of quasi-spherical, negatively charged citrate-stabilized TC-AuNPs with an average size of 55 ± 5 nm. UV-vis spectroscopy was employed to determine the stability range of the conjugates under controlled conditions of pH and ionic strength. Based on electrokinetic measurements, it was observed that the zeta potential of CPZ-AuNP conjugates strongly depends on the amount of CPZ adsorbed on the TC-AuNP surface. Additionally, the conjugates exhibited an isoelectric point at pH 8.8. Surface-enhanced Raman spectroscopy (SERS) and surface-enhanced infrared absorption spectroscopy (SEIRA) were employed to elucidate the adsorption structure of CPZ on TC-AuNPs. The interpretation of the spectra was conducted based on the Raman and FTIR spectra of CPZ, along with calculations performed using Density Functional Theory (DFT). The results indicated that CPZ primarily interacts with the TC-AuNP surface through the angularly oriented phenothiazine ring and the propylene bridge. Furthermore, it was demonstrated that the C-N-C fragment is perpendicular to the surface of the TC-AuNP with which it interacts. The findings from this analysis suggest the potential for further research on the use of these conjugates in biomedical applications.
PubMed: 38870699
DOI: 10.1016/j.saa.2024.124588 -
Nanoscale Advances Jun 2024We present the design and synthesis of two new organic polymer films making use of a liquid-liquid interfacial amine-acid chloride polymerization strategy. One of them...
We present the design and synthesis of two new organic polymer films making use of a liquid-liquid interfacial amine-acid chloride polymerization strategy. One of them was additionally functionalized by the anchoring of -phenyl-phenothiazine through a monomer truncation strategy, which endowed it with photocatalytic activity. This photoactive film displays interesting luminescence phenomena that were used for the oxidation of a variety of sulphides to their corresponding sulfoxides and reduction of aryl bromines.
PubMed: 38868836
DOI: 10.1039/d4na00149d -
International Journal of Colorectal... Jun 2024Discussions about the optimal lymph node (LN) count and its therapeutic consequences have persisted over time. The final LN count in colorectal tissues is affected by a...
INTRODUCTION
Discussions about the optimal lymph node (LN) count and its therapeutic consequences have persisted over time. The final LN count in colorectal tissues is affected by a variety of variables (patient, tumor, operation, pathologist, immune response). Methylene blue (MB) intra-arterial injection is a simple and inexpensive procedure that can be used to enhance lymph node count.
AIM
Analyze whether there is a statistically significant difference between intra-arterial methylene blue injection and conventional dissection for the quantification of lymph nodes and determine if there is a variation in the quality of lymph node acquisition.
METHODS AND RESULTS
Between 2015 and 2022, we conducted a retrospective analysis of colon cancer specimens. Data on the tumor's features, the number of lymph nodes, the number of lymph nodes that were positive, and other factors had been collected. The number of identified lymph nodes was highly significantly improved in the study group (P < 0.05). There is not a significant statistical difference between groups regarding the metastatic lymph node harvest. The group with injection of intra-arterial methylene blue shows a significantly decreased (P < 0.05) of the of cases with less than 12 lymph nodes recovered comparing with the control group.
CONCLUSION
Colon cancer specimens can be easily evaluated concerning lymph nodes using the methylene blue method. Therefore, we strongly advise this approach as a standard procedure in the histological evaluation of colon cancer specimens in order to maximize the identification of lymph nodes. However, the detection of metastatic lymph nodes was unaffected significantly.
Topics: Humans; Methylene Blue; Colonic Neoplasms; Retrospective Studies; Male; Female; Middle Aged; Aged; Lymph Nodes; Lymphatic Metastasis; Aged, 80 and over; Adult
PubMed: 38866990
DOI: 10.1007/s00384-024-04663-2 -
Colloids and Surfaces. B, Biointerfaces Jun 2024The pressing need for highly efficient antibacterial strategies arises from the prevalence of microbial biofilm infections and the emergence of rapidly evolving...
The pressing need for highly efficient antibacterial strategies arises from the prevalence of microbial biofilm infections and the emergence of rapidly evolving antibiotic-resistant strains of pathogenic bacteria. Photodynamic therapy represents a highly efficient and compelling antibacterial approach, offering promising prospects for effective control of the development of bacterial resistance. However, the effectiveness of many photosensitizers is limited due to the reduced generation of reactive oxygen species (ROS) in hypoxic microenvironment, which commonly occur in pathological conditions such as inflammatory and bacteria-infected wounds. Herein, we designed and prepared two phenothiazine-derived photosensitizers (NB-1 and NB-2), which can effectively generate superoxide anion radicals (O) through the type I process. Both photosensitizers demonstrate significant efficacy in vitro for the eradication of broad-spectrum bacteria. Moreover, NB-2 possesses distinct advantages including strong membrane binding and strong generation of O, rendering it an exceptionally efficient antibacterial agent against mature biofilms. In addition, laser activated NB-2 could be applied to treat MRSA-infected wound in vivo, which offers new opportunities for potential practical applications.
PubMed: 38865868
DOI: 10.1016/j.colsurfb.2024.114018 -
Environmental Geochemistry and Health Jun 2024In the pursuit of efficient photocatalytic materials for environmental applications, a new series of g-CN/N-doped CeO nanocomposites (g-CN/N-CeO NCs) was synthesized...
In the pursuit of efficient photocatalytic materials for environmental applications, a new series of g-CN/N-doped CeO nanocomposites (g-CN/N-CeO NCs) was synthesized using a straightforward dispersion method. These nanocomposites were systematically characterized to understand their structural, optical, and chemical properties. The photocatalytic performance of g-CN/N-CeO NCs was evaluated by investigating their ability to degrade methylene blue (MB) dye, a model organic pollutant. The results demonstrate that the integration of g-CN with N-doped CeO NCs reduces the optical energy gap compared to pristine N-doped CeO, leading to enhanced photocatalytic efficiency. It is benefited from the existence of g-CN/N-CeO NCs not only in promoting the charge separation and inhibits the fast charge recombination but also in improving photocatalytic oxidation performance. Hence, this study highlights the potential of g-CN/N-CeO NCs as promising candidates for various photocatalytic applications, contributing to the advancement of sustainable environmental remediation technologies.
Topics: Methylene Blue; Cerium; Nanocomposites; Catalysis; Light; Water Pollutants, Chemical; Graphite; Photochemical Processes; Photolysis; Nitrogen Compounds
PubMed: 38864996
DOI: 10.1007/s10653-024-02007-1 -
Luminescence : the Journal of... Jun 2024In this study, tellurium-doped and undoped metal oxide nanoparticles (NPs) (ZnO, MnO, SnO) are compared, and a practical method for their synthesis is presented.... (Comparative Study)
Comparative Study
In this study, tellurium-doped and undoped metal oxide nanoparticles (NPs) (ZnO, MnO, SnO) are compared, and a practical method for their synthesis is presented. Nanocomposites were created using the coprecipitation process, and comparisons between the three material categories under study were made using a range of characterization methods. The produced materials were subjected to structural, morphological, elemental composition, and functional group analyses using XRD, FESEM in combination with EDS, and FTIR. The optical characteristics in terms of cutoff wavelength were evaluated using UV-visible spectroscopy. Catalyzing the breakdown of methylene blue (MB) dye, the isolated nanocomposites demonstrated very consistent behavior when utilized as catalysts. Regarding both doped and undoped ZnO NPs, the maximum percentage of degradation was found to be 98% when exposed to solar Escherichia coli and Staphylococcus aureus, which stand for gram-positive and gram-negative bacteria, respectively, and were chosen as model strains for both groups using the disk diffusion technique in the context of in vitro antibacterial testing. Doped and undoped ZnO NPs exhibited greater antibacterial efficacy, with significant inhibition zones measuring 31.5 and 37.8 mm, compared with other metal oxide NPs.
Topics: Anti-Bacterial Agents; Tellurium; Staphylococcus aureus; Catalysis; Metal Nanoparticles; Escherichia coli; Microbial Sensitivity Tests; Photochemical Processes; Methylene Blue; Zinc Oxide; Manganese; Tin; Particle Size; Oxides
PubMed: 38858760
DOI: 10.1002/bio.4799 -
Arthritis Research & Therapy Jun 2024Primary osteoarthritis (OA) occurs without identifiable underlying causes such as previous injuries or specific medical conditions. Age is a major contributing factor to...
BACKGROUND
Primary osteoarthritis (OA) occurs without identifiable underlying causes such as previous injuries or specific medical conditions. Age is a major contributing factor to OA, and as one ages, various joint tissues undergo gradual change, including degeneration of the articular cartilage, alterations in subchondral bone (SCB) morphology, and inflammation of the synovium.
METHODS
We investigated the prevalence of primary OA in aged, genetically diverse UM-HET3 mice. Articular cartilage (AC) integrity and SCB morphology were assessed in 182 knee joints of 22-25 months old mice using the Osteoarthritis Research Society International (OARSI) scoring system and micro-CT, respectively. Additionally, we explored the effects of methylene blue (MB) and mitoquinone (MitoQ), two agents that affect mitochondrial function, on the prevalence and progression of OA during aging.
RESULTS
Aged UM-HET3 mice showed a high prevalence of primary OA in both sexes. Significant positive correlations were found between cumulative AC (cAC) scores and synovitis in both sexes, and osteophyte formation in female mice. Ectopic chondrogenesis did not show significant correlations with cAC scores. Significant direct correlations were found between AC scores and inflammatory markers in chondrocytes, including matrix metalloproteinase-13, inducible nitric oxide synthase, and the NLR family pyrin domain containing-3 inflammasome in both sexes, indicating a link between OA severity and inflammation. Additionally, markers of cell cycle arrest, such as p16 and β-galactosidase, also correlated with AC scores. In male mice, no significant correlations were found between SCB morphology traits and cAC scores, while in female mice, significant correlations were found between cAC scores and tibial SCB plate bone mineral density. Notably, MB and MitoQ treatments influenced the disease's progression in a sex-specific manner. MB treatment significantly reduced cAC scores at the medial knee joint, while MitoQ treatment reduced cAC scores, but these did not reach significance.
CONCLUSIONS
Our study provides comprehensive insights into the prevalence and progression of primary OA in aged UM-HET3 mice, highlighting the sex-specific effects of MB and MitoQ treatments. The correlations between AC scores and various pathological factors underscore the multifaceted nature of OA and its association with inflammation and subchondral bone changes.
Topics: Animals; Male; Female; Mice; Aging; Osteoarthritis; Cartilage, Articular; Methylene Blue; Ubiquinone; Disease Models, Animal; Disease Progression
PubMed: 38851726
DOI: 10.1186/s13075-024-03349-y -
Chemosphere Aug 2024Titanium dioxide nanoparticles (TiO-NP) present in wastewater effluent are discharged into freshwater and saltwater (i.e., marine) systems. TiO-NP can be solar-driven...
Titanium dioxide nanoparticles (TiO-NP) present in wastewater effluent are discharged into freshwater and saltwater (i.e., marine) systems. TiO-NP can be solar-driven photoactivated by ultraviolet (UV)-light producing reactive oxygen species including hydroxyl radicals (·OH). ·OH are non-selective and react with a broad range of species in water. In other studies, photoactivation of TiO-NP has been correlated with oxidative stress and ecotoxicological impacts on plant and animal biota. This study examined the photoactivation of TiO-NP in freshwater and saltwater systems, and contrasted the oxidation potential in both systems using methylene blue (MB) as a reaction probe. Maximum MB loss (51.9%, n = 4; 95% confidence interval 49.4-54.5) was measured in salt-free, deionized water where ·OH scavenging was negligible; minimum MB loss (1%) was measured in saltwater due to significant ·OH scavenging, indicating the inverse correlation between MB loss and radical scavenging. A kinetic analysis of scavenging by seawater constituents indicated Cl had the greatest impact due to high concentration and high reaction rate constant. Significant loss of MB occurred in the presence of Br relative to other less aggressive scavengers present in seawater (i.e., HCO, HSO). This result is consistent with the formation of Bromate, a strong oxidant that subsequently reacts with MB. In freshwater samples collected from different water bodies in Oklahoma (n = 12), the average MB loss was 13.4%. Greater MB loss in freshwater systems relative to marine systems was due to lower ·OH scavenging by various water quality parameters. Overall, TiO-NP photoactivation in freshwater systems has the potential to cause greater oxidative stress and ecotoxicological impacts than in marine systems where ·OH scavenging is a dominant reaction.
Topics: Titanium; Fresh Water; Oxidation-Reduction; Seawater; Free Radical Scavengers; Water Pollutants, Chemical; Hydroxyl Radical; Nanoparticles; Ultraviolet Rays; Wastewater; Methylene Blue
PubMed: 38851501
DOI: 10.1016/j.chemosphere.2024.142549 -
Environmental Geochemistry and Health Jun 2024This study reported the synthesis and assessment of zinc oxide/iron oxide (ZnO/FeO) nanocomposite as photocatalysts for the degradation of a mixture of methylene red and...
This study reported the synthesis and assessment of zinc oxide/iron oxide (ZnO/FeO) nanocomposite as photocatalysts for the degradation of a mixture of methylene red and methylene blue dyes. X-ray diffraction analysis confirms that the crystallite of zinc oxide (ZnO) has a hexagonal wurtzite phase and iron oxide (FeO) has a rhombohedral phase. Fourier Transform Infra-Red spectrum confirms the presence of Zn-O vibration stretching at 428, 480 and 543 cm stretching confirming Fe-O bond formation. Scanning Electron Microscope images exhibited a diverse size and shape of the nanocomposites. The ZnO-90%/FeO-10% and ZnO-10%/FeO-90% nanocomposites reveal good photocatalytic activity with reaction rate constants of 1.5 × 10 and 0.66 × 10; and 1.3 × 10 and 0.60 × 10 for methylene blue and methyl red dye respectively. The results revealed that the synthesized ZnO/FeO nanocomposite is the best catalyst for dye degradation and can be used for industrial applications in future.
Topics: Zinc Oxide; Nanocomposites; Methylene Blue; Ferric Compounds; Catalysis; Coloring Agents; X-Ray Diffraction; Microscopy, Electron, Scanning; Azo Compounds; Water Pollutants, Chemical; Photolysis; Spectroscopy, Fourier Transform Infrared
PubMed: 38849635
DOI: 10.1007/s10653-024-02000-8