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Chemico-biological Interactions May 2024RNA plays an important role in many biological processes which are crucial for cell survival, and it has been suggested that it may be possible to inhibit individual...
Interaction of 3,9-disubstituted acridine with single stranded poly(rA), double stranded poly(rAU) and triple stranded poly(rUAU): molecular docking - A spectroscopic tandem study.
RNA plays an important role in many biological processes which are crucial for cell survival, and it has been suggested that it may be possible to inhibit individual processes involved in many diseases by targeting specific sequences of RNA. The aim of this work is to determine the affinity of novel 3,9-disubstited acridine derivative 1 with three different RNA molecules, namely single stranded poly(rA), double stranded homopolymer poly(rAU) and triple stranded poly(rUAU). The results of the absorption titration assays show that the binding constant of the novel derivative to the RNA molecules was in the range of 1.7-6.2 × 10 mol dm. The fluorescence and circular dichroism titration assays revealed considerable changes. The most significant results in terms of interpreting the nature of the interactions were the melting temperatures of the RNA samples in complexes with the 1. In the case of poly(rA), denaturation resulted in a self-structure formation; increased stabilization was observed for poly(rAU), while the melting points of the ligand-poly(rUAU) complex showed significant destabilization as a result of the interaction. The principles of molecular mechanics were applied to propose the non-bonded interactions within the binding complex, pentariboadenylic acid and acridine ligand as the study model. Initial molecular docking provided the input structure for advanced simulation techniques. Molecular dynamics simulation and cluster analysis reveal π - π stacking and the hydrogen bonds formation as the main forces that can stabilize the binding complex. Subsequent MM-GBSA calculations showed negative binding enthalpy accompanied the complex formation and proposed the most preferred conformation of the interaction complex.
Topics: Acridines; Molecular Docking Simulation; Poly A; Circular Dichroism; Thermodynamics; Spectrometry, Fluorescence; RNA; Nucleic Acid Conformation
PubMed: 38552767
DOI: 10.1016/j.cbi.2024.110965 -
Ecotoxicology and Environmental Safety Apr 2024Endogenous immune defenses provide an intrinsic barrier against external entity invasion. Microplastics in the environment, especially those at the nanoscale...
Endogenous immune defenses provide an intrinsic barrier against external entity invasion. Microplastics in the environment, especially those at the nanoscale (nanoplastics or NPs), may pose latent health risks through direct exposure. While links between nanoplastics and inflammatory processes have been established, detailed insights into how they may perturb the innate immune mechanisms remain uncharted. Employing murine and macrophage (RAW264.7) cellular models subjected to polystyrene nanoplastics (PS-NPs), our investigative approach encompassed an array of techniques: Cell Counting Kit-8 assays, flow cytometric analysis, acridine orange/ethidium bromide (AO/EB) fluorescence staining, cell transfection, cell cycle scrutiny, genetic manipulation, messenger RNA expression profiling via quantitative real-time PCR, and protein expression evaluation through western blotting. The results showed that PS-NPs caused RAW264.7 cell apoptosis, leading to cell cycle arrest, and activated the cGAS-STING pathway. This resulted in NF-κB signaling activation and increased pro-inflammatory mediator expression. Importantly, PS-NPs-induced activation of NF-κB and its downstream inflammatory cascade were markedly diminished after the silencing of the STING gene. Our findings highlight the critical role of the cGAS-STING pathway in the immunotoxic effects induced by PS-NPs. We outline a new mechanism whereby nanoplastics may trigger dysregulated innate immune and inflammatory responses via the cGAS/STING pathway.
Topics: Animals; Mice; Microplastics; NF-kappa B; Plastics; Polystyrenes; Immunity, Innate; Nucleotidyltransferases
PubMed: 38552388
DOI: 10.1016/j.ecoenv.2024.116255 -
RSC Advances Mar 2024A method for synthesizing xanthene and acridine derivatives using transition metal catalysts supported by de-alumination zeolite-NaY is described. Some transition metal...
A method for synthesizing xanthene and acridine derivatives using transition metal catalysts supported by de-alumination zeolite-NaY is described. Some transition metal ion-exchanged NaY zeolite was prepared and evaluated in a reaction toward the synthesis of xanthene and acridine. The most active catalyst in this field is a heterogeneous copper/zeolite catalyst. The synthesis of xanthene with a wide range of aldehydes/dimedone with a molar ratio of 1/2 and acridine synthesis with a molar ratio of dimedone/aromatic/ammonium nitrate of 2/1/1 was carried out in one pot and solvent-free conditions. Sensing in the presence of supported metal catalysts is operationally simple, does not require expensive or toxic reagents, and gives high yields in a short period.
PubMed: 38549799
DOI: 10.1039/d3ra03020b -
Diseases of Aquatic Organisms Mar 2024In the 1980s, a mass die-off of the long-spined sea urchin Diadema antillarum occurred on Florida and Caribbean coral reefs. D. antillarum populations largely did not...
In the 1980s, a mass die-off of the long-spined sea urchin Diadema antillarum occurred on Florida and Caribbean coral reefs. D. antillarum populations largely did not recover, and in 2022, remaining populations experienced another mass mortality event. A ciliate most similar to Philaster apodigitiformis was identified as the causative agent of the 2022 event, which was named D. antillarum scuticociliatosis (DaSc). Here, we investigated possible treatments for this pathogen. We tested the efficacy of 10 compounds at final concentrations of 100, 50, 25, 12.5, 6.25, and 3.13 µM, or a 10-fold serial dilution series, against ciliates cultured from an infected D. antillarum specimen. Of the tested compounds, 8 induced 100% ciliate mortality at some dose after 24 h. The most effective (defined as those requiring the lowest dose to induce 100% ciliate mortality) were quinacrine and tomatine (both effective at 12.5 µM), followed by furaltadone and plumbagin (25 µM), bithionol sulfoxide and 2'4' dihydroxychalcone (50 µM), and oxyclozanide and carnidazole (100 µM). Toltrazuril and a commercially available anticiliate product containing naphthoquinones were not effective at any dose tested. Shortened (15 min) time trials were performed using ciliate cultures reared in natural seawater to better reflect natural environmental conditions, and revealed that 2 of the compounds (quinacrine and tomatine) induced 100% ciliate mortality at 100 µM, with tomatine also effective at 50 µM. This study identified several treatments effective against the causative agent of DaSc in vitro, but their toxicity and utility in vivo remain unknown.
Topics: Animals; Tomatine; Sea Urchins; Coral Reefs; Ciliophora; Quinacrine
PubMed: 38546194
DOI: 10.3354/dao03776 -
Molecules (Basel, Switzerland) Mar 2024Iodine, primarily in the form of iodide (I), is the bioavailable form for the thyroid in the human body. Both deficiency and excess intake of iodide can lead to serious...
Iodine, primarily in the form of iodide (I), is the bioavailable form for the thyroid in the human body. Both deficiency and excess intake of iodide can lead to serious health issues, such as thyroid disease. Selecting iodide ions among anions has been a significant challenge for decades due to interference from other anions. In this study, we designed and synthesized a new pincer-type acridine-triazole fluorescent probe (probe ) with an acridine ring as a spacer and a triazole as a linking arm attached to two naphthol groups. This probe can selectively recognize iodide ions in a mixed solvent of THF/HO (/, 9/1), changing its color from colorless to light yellow, making it suitable for highly sensitive and selective colorimetric and fluorescent detection in water systems. We also synthesized another molecular tweezer-type acridine-triazole fluorescent probe (probe ) that exhibits uniform detection characteristics for iodide ions in the acetonitrile system. Interestingly, compared to probe , probe can be detected by the naked eye due to its circulation effect, providing a simple method for iodine detection. The detection limit of probe is determined to be 10 mol·L by spectrometric titration and isothermal titration calorimetry measurements. The binding stoichiometry between probe and iodide ions is calculated to be 1:1 by these methods, and the binding constant is 2 × 10 mol·L.
PubMed: 38542992
DOI: 10.3390/molecules29061355 -
Cells Mar 2024Semen handling and cryopreservation induce oxidative stress that should be minimized. In this study, human semen was supplemented during cryopreservation with...
Semen handling and cryopreservation induce oxidative stress that should be minimized. In this study, human semen was supplemented during cryopreservation with formulations of handmade liposomes and chlorogenic acid (CGA), an antioxidant compound. Zwitterionic (ZL), anionic (AL), and cationic (CL) liposomes were synthesized and characterized. Three aliquots of swim-up-selected sperm were incubated with ZL, AL, and CL (1:10,000), respectively. The percentages of sperm with progressive motility, high mitochondrial membrane potential (MMP; JC-1), double-stranded DNA (dsDNA acridine orange), and acrosome integrity ( agglutinin) were assessed. Then, human semen was frozen using both 1:10,000 ZL and CGA as follows: freezing medium/empty ZL (EL), freezing medium/empty ZL/CGA in the medium (CGA + EL), freezing medium/CGA loaded ZL (CGA), freezing medium (CTR). The same sperm endpoints were evaluated. ZL were the most tolerated and used for semen cryopreservation protocols. All the supplemented samples showed better endpoints versus CTR ( < 0.001). In particular, spermatozoa from the CGA and CGA + EL A samples showed increased motility, dsDNA, and acrosome integrity versus CTR and EL ( < 0.001; motility EL vs. CGA + EL < 0.05). ZL and CGA can improve post-thaw sperm quality, acting on both cold shock effect management and oxidative stress. These findings open new perspectives on human and animal reproduction.
Topics: Animals; Humans; Male; Freezing; Chlorogenic Acid; Liposomes; Fertility Preservation; Cryoprotective Agents; Semen Preservation; Seeds; Spermatozoa; Cryopreservation; Dietary Supplements
PubMed: 38534386
DOI: 10.3390/cells13060542 -
Cells Mar 2024Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway that functions in nutrient recycling and as a mechanism of innate immunity. Previously, we...
Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway that functions in nutrient recycling and as a mechanism of innate immunity. Previously, we reported a novel host-bacteria interaction between cariogenic and bitter taste receptor (T2R14) in gingival epithelial cells (GECs), leading to an innate immune response. Further, might be using the host immune system to inhibit other Gram-positive bacteria, such as . To determine whether these bacteria exploit the autophagic machinery of GEC, it is first necessary to evaluate the role of T2R14 in modulating autophagic flux. So far, the role of T2R14 in the regulation of autophagy is not well characterized. Therefore, in this study, for the first time, we report that T2R14 downregulates autophagy flux in GECs, and T2R14 knockout increases acidic vacuoles. However, the treatments of GEC WT with a T2R14 agonist and antagonist did not lead to a significant change in acidic vacuole formation. Transmission electron microscopy morphometric results also suggested an increased number of autophagic vesicles in T2R14-knockout GEC. Further, our results suggest that competence stimulating peptide CSP-1 showed robust intracellular calcium release and this effect is both T2R14- and autophagy protein 7-dependent. In this study, we provide the first evidence that T2R14 modulates autophagy flux in GEC. The results of the current study could help in identifying the impact of T2R in regulation of the immuno-microenvironment of GEC and subsequently oral health.
Topics: Taste; Receptors, G-Protein-Coupled; Staphylococcus aureus; Autophagy; Epithelial Cells
PubMed: 38534375
DOI: 10.3390/cells13060531 -
BioMedicine 2023Gemcitabine is frequently utilized to treat pancreatic cancer. The purpose of our study was to create a gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cell line...
Gemcitabine is frequently utilized to treat pancreatic cancer. The purpose of our study was to create a gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cell line (MIA-GR100) and to evaluate the anti-pancreatic cancer efficacy of HMJ-38, a new quinazolinone analogue. Compared to their parental counterparts, MIA-PaCa-2, established MIA-GR100 cells were less sensitive to gemcitabine. MIA-GR100 cell viability was not affected by 10, 50 and 100 nM gemcitabine concentrations. HMJ-38 reduced MIA-GR100 cell growth and induced autophagy and apoptosis. When stained with monodansylcadaverine (MDC), acridine orange (AO), and terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), MIA-GR100 cells shrunk, punctured their membranes, and produced autophagy vacuoles and apoptotic bodies. Combining chloroquine (CQ) and 3-methyladenine (3-MA) with HMJ-38 dramatically reduced cell viability, indicating that autophagy function as a cytoprotective mechanism. MIA-GR100 cells treated with both z-VAD-FMK and HMJ-38 were much more viable than those treated with HMJ-38 alone. HMJ-38 promotes apoptosis in MIA-GR100 cells by activating caspases. Epidermal growth factor receptor (EGFR) is one of HMJ-38's principal targets, as determined target screening with network prediction. HMJ-38 also inhibited EGFR kinase activity and EGFR-associated signaling in MIA-GR100 cells. HMJ-38 may be an effective chemotherapeutic adjuvant for gemcitabine-resistant pancreatic cancer cells, in which it induces an antitumor response.
PubMed: 38532833
DOI: 10.37796/2211-8039.1423 -
Turkish Journal of Pharmaceutical... Mar 2024Humans are unknowingly exposed to mycotoxins through the consumption of plant-derived foods and processed products contaminated with these toxic compounds. In addition...
OBJECTIVES
Humans are unknowingly exposed to mycotoxins through the consumption of plant-derived foods and processed products contaminated with these toxic compounds. In addition to agricultural losses, Fusarium toxins pose a threat to human health. However, the effects of fusariotoxins on the viability and proliferation of stem cells have not been fully explored. We investigated the cytotoxic effects of deoxynivalenol (DON) and B-trichothecene mix (MIX) on mesenchymal stem cells (MSCs) and the L929 fibroblast cell line.
MATERIALS AND METHODS
MSCs were isolated from the dental pulp tissue. The doubling time and viability of dental pulp stem cells (DPSCs) and L929 cells were determined using the MTT assay. The following doses of B-trichothecenes (0.25-16 µg/mL; 24 hours and 48 hours) were used to evaluate cytotoxicity. In addition, changes in the confluency-dependent response of DPSCs to DON toxicity were determined. Moreover, we investigated the effect of DON on cell death acridine orange/ethidium bromide (AO/EB) double staining.
RESULTS
A DON and MIX showed a dose- and time-dependent inhibitory effect on the proliferation of both cells. DPSCs exposed to DON for 48 hours (IC = 0.5 μg/mL) were found to be 16-fold more sensitive than L929 cells (IC = 8 μg/mL). Compared with a culture with 80% confluency, DPSCs from a 50% confluent culture were more sensitive to varying doses of DON (0.25-4 µg/mL, 24-48 hours). Moreover, AO/EB staining showed that treatment of DPSCs with DON led to a significant increase in cell death (17% for 2.4 µg/mL; 50% for 4.8 µg/mL).
CONCLUSION
This study reveals that undifferentiated MSCs are significantly more sensitive to DON than differentiated somatic cells (L929). Given that humans are frequently exposed to these mycotoxins, our findings imply that prolonged exposure to them may also have harmful effects on cellular differentiation and embryonic development.
PubMed: 38529558
DOI: 10.4274/tjps.galenos.2023.76128 -
Cureus Feb 2024Citicoline and cerebrolysin are two unique yet contentious medications because of inconsistencies in efficacy as well as the mystery surrounding their mode of action....
Neuroprotection by Cerebrolysin and Citicoline Through the Upregulation of Brain-Derived Neurotrophic Factor (BDNF) Expression in the Affected Neural Cells: A Preliminary Clue Obtained Through an In Vitro Study.
OBJECTIVES
Citicoline and cerebrolysin are two unique yet contentious medications because of inconsistencies in efficacy as well as the mystery surrounding their mode of action. The current study aimed to re-validate the neuroprotective benefits of these medications and investigate the possible molecular mechanism.
METHODS
Neuro-2A cells were exposed to tert-butyl hydroperoxide, a consistent in vitro model of neuronal damage caused by oxidative stress. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, acridine orange/ethidium bromide (AO-EtBr) staining, and phase-view examinations were utilized to evaluate cell survival and cytotoxicity. Real-time reverse transcription-polymerase chain reaction (RT-PCR)-based gene expression studies were conducted.
KEY FINDING
Observations revealed that these two medications had modest but considerable neuroprotective effects. While the majority of the genes' expressions remained unchanged, cerebrolysin upregulated Neuregulin 1, and both upregulated brain-derived neurotrophic factor (BDNF) expression.
CONCLUSION
The findings of the current study may be the first to suggest that citicoline and cerebrolysin may increase host cells' defense mechanisms (secretion neurotrophic factors) rather than carrying nutrients for cell survival. Because of its simplicity, the current study can readily be repeated to learn more about these two disputed medications for treating ischemic stroke.
PubMed: 38524067
DOI: 10.7759/cureus.54665