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National Science Review Jul 2024Covalent-organic frameworks (COFs) with photoinduced donor-acceptor (D-A) radical pairs show enhanced photocatalytic activity in principle. However, achieving long-lived...
Covalent-organic frameworks (COFs) with photoinduced donor-acceptor (D-A) radical pairs show enhanced photocatalytic activity in principle. However, achieving long-lived charge separation in COFs proves challenging due to the rapid charge recombination. Here, we develop a novel strategy by combining [6 + 4] nodes to construct -type 3D COFs, first reported in COF chemistry. This structure type exhibits a fused Olympic-rings-like shape, which provides a platform for stabilizing the photoinduced D-A radical pairs. The -type COFs containing catalytically active moieties such as triphenylamine and phenothiazine (PTZ) show superior photocatalytic production rates of hydrogen peroxide (HO). Significantly, the photochromic radical states of these COFs show up to 400% enhancement in photocatalytic activity compared to the parent states, achieving a remarkable HO synthesis rate of 3324 μmol g h, which makes the PTZ-COF one of the best crystalline porous photocatalysts in HO production. This work will shed light on the synthesis of efficient 3D COF photocatalysts built on topologies that can facilitate photogenerating D-A radical pairs for enhanced photocatalysis.
PubMed: 38883289
DOI: 10.1093/nsr/nwae177 -
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 -
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 -
Chemical Science Jun 2024The capability of organic emitters to harvest triplet excitons a thermally activated delayed fluorescence (TADF) process has opened a new era in organic...
The capability of organic emitters to harvest triplet excitons a thermally activated delayed fluorescence (TADF) process has opened a new era in organic optoelectronics. Nevertheless, low brightness, and consequently an insufficient roll-off ratio, constitutes a bottleneck for their practical applications in the domain of organic light-emitting diodes (OLEDs). To address this formidable challenge, we developed a new design of desymmetrized naphthalimide (NMI) featuring an annulated indole with a set of auxiliary donors on its periphery. Their perpendicular arrangement led to minimized HOMO-LUMO overlap, resulting in a low energy gap (Δ = 0.05-0.015 eV) and efficient TADF emission with a photoluminescence quantum yield (PLQY) ranging from 82.8% to 95.3%. Notably, the entire set of dyes (NMI-Ind-TBCBz, NMI-Ind-DMAc, NMI-Ind-PXZ, and NMI-Ind-PTZ) was utilized to fabricate TADF OLED devices, exhibiting yellow to red electroluminescence. Among them, red-emissive NMI-Ind-PTZ, containing phenothiazine as an electron-rich component, revealed predominant performance with a maximum external quantum efficiency (EQE) of 23.6%, accompanied by a persistent luminance of 38 000 cd m. This results in a unique roll-off ratio (EQE = 21.6%), delineating a straightforward path for their commercial use in lighting and display technologies.
PubMed: 38846379
DOI: 10.1039/d4sc01391c -
Scientific Reports May 2024Voriconazole is a second-generation azole used to treat serious fungal infections. Visual hallucinations constitute a representative adverse event caused by...
Association between voriconazole-induced visual hallucination and dopamine in an analysis of the food and drug administration (FDA) adverse event reporting system database.
Voriconazole is a second-generation azole used to treat serious fungal infections. Visual hallucinations constitute a representative adverse event caused by voriconazole. However, its mechanism of action remains unclear. In patients with schizophrenia or Parkinson's disease, the frequency of visual hallucinations is associated with brain dopamine levels. This study investigated the frequency of visual hallucinations in patients treated with voriconazole alone or in combination with dopaminergic medicines or dopamine antagonists, using data collected from the Food and Drug Administration Adverse event Reporting System (FAERS). The frequency of visual hallucinations with voriconazole alone and in combination with a dopaminergic medicine (levodopa) or dopamine antagonists (risperidone and chlorpromazine) was compared using data from the FAERS between 2004 and 2023, using the reporting odds ratio (ROR) with relevant 95% confidence intervals (CI). The reference group comprised patients who had been administered voriconazole without dopaminergic medication or dopamine antagonists. Of the patients, 22,839, 90,810, 109,757, 6,435, 20, 83, and 26, respectively were treated with voriconazole, levodopa, risperidone, chlorpromazine, voriconazole plus levodopa, voriconazole plus risperidone, and voriconazole plus chlorpromazine. The occurrence of visual hallucinations increased when used in combination with levodopa (ROR = 12.302, 95% CI = 3.587-42.183). No increase in incidence was associated with the concomitant use of dopamine antagonists (risperidone, ROR = 1.721, 95% CI = 0.421-7.030; chlorpromazine, ROR = none, 95% CI = none). Dopaminergic medicine may increase the risk of visual hallucinations in patients treated with voriconazole. Whether voriconazole positively modulates dopamine production warrants further investigation using a translational research approach.
Topics: Humans; Voriconazole; Hallucinations; United States; United States Food and Drug Administration; Male; Female; Aged; Middle Aged; Dopamine; Levodopa; Adult; Antifungal Agents; Adverse Drug Reaction Reporting Systems; Chlorpromazine; Risperidone; Dopamine Antagonists; Parkinson Disease; Young Adult; Adolescent; Databases, Factual
PubMed: 38822123
DOI: 10.1038/s41598-024-63504-y -
Scientific Reports May 2024Photocatalysts of TiO-CuO coupled with 30% graphene oxide (GO) were hydrothermally fabricated, which varied the TiO to CuO weight ratios to 1:4, 1:2, 1:1, 2:1 and 4:1...
Photocatalysts of TiO-CuO coupled with 30% graphene oxide (GO) were hydrothermally fabricated, which varied the TiO to CuO weight ratios to 1:4, 1:2, 1:1, 2:1 and 4:1 and reduced to form TiO-CuO/reduced graphene oxide (rGO) photocatalysts. They were characterized using XRD, TEM, SEM, XPS, Raman, and DRS technologies. TiO-CuO composites and TiO-CuO/GO degrade methylene blue when persulfate ions are present. Persulfate concentration ranged from 1, 2, 4 to 8 mmol/dm in which the highest activity of 4.4 × 10 and 7.35 × 10 min was obtained with 4 mmol/dm for TiO-CuO (1:4) and TiO-CuO/GO (1:1), respectively. The presence of EDTA and isopropyl alcohol reduced the photodegradation. TiO-CuO coupled with rGO coagulates methylene blue in the presence of persulfate ions and such coagulation is independent of light. The catalyst dosage and the concentration of the dye were varied for the best-performing samples. The antibacterial activity of the synthesized samples was evaluated against the growth of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumonia. Ti:Cu (1:2)-GO and Ti:Cu (1:4)-GO had the highest antibacterial activity against K. pneumoniae (16.08 ± 0.14 mm), P. aeruginosa (22.33 ± 0.58 mm), E. coli (16.17 ± 0.29 mm) and S. aureus (16.08 ± 0.88).
Topics: Graphite; Titanium; Copper; Anti-Bacterial Agents; Catalysis; Methylene Blue; Escherichia coli; Staphylococcus aureus; Photolysis; Sulfates
PubMed: 38822052
DOI: 10.1038/s41598-024-63452-7 -
Drugs & Aging Jun 2024Most drugs have not been evaluated in the older population. Recognizing physiological alterations associated with changes in drug disposition and with the ultimate... (Review)
Review
Most drugs have not been evaluated in the older population. Recognizing physiological alterations associated with changes in drug disposition and with the ultimate effect, especially in central nervous system-acting drugs, is fundamental. While considering pharmacokinetics, it should be noted that the absorption of most drugs from the gastrointestinal tract does not change in advanced age. There are only few data about the effect of age on the transdermal absorption of medications such as fentanyl. Absorption from an intramuscular injection may be similar in older adults as in younger patients. The distribution of lipophilic drugs (such as diazepam) is increased owing to a relative increase in the percentage of body fat, causing drug accumulation and prolonged drug elimination following cessation. Phase I drug biotransformation is variably decreased in aging, impacting elimination, and hepatic drug clearance has been shown to decrease in older individuals by 10-40% for most drugs studied. Lower doses of phenothiazines, butyrophenones, atypical antipsychotics, antidepressants (citalopram, mirtazapine, and tricyclic antidepressants), and benzodiazepines (such as diazepam) achieve the same extent of exposure. For renally cleared drugs with no prior metabolism (such as gabapentin), the glomerular filtration rate appropriately estimates drug clearance. Important pharmacodynamic changes in older adults include an increased sedative effect of benzodiazepines at a given drug exposure, and a higher sensitivity to mu opiate receptor agonists and to opioid adverse effects. Artificial intelligence, physiologically based pharmacokinetic modeling and simulation, and concentration-effect modeling enabling a differentiation between the pharmacokinetic and the pharmacodynamic effects of aging might help to close some of the gaps in knowledge.
Topics: Humans; Aged; Central Nervous System Agents; Aging
PubMed: 38814377
DOI: 10.1007/s40266-024-01117-w