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Results for “Galantamine”

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Single-cell transcriptomics reveals distinct microglial state remodeling associated with the (R)-nicotine/diosmetin combination and galantamine in LPS-challenged BV2 cells.

BACKGROUND: Microglial neuroinflammation contributes to the progression of neurodegenerative diseases, yet it remains challenging to attenuate inflammatory responses while preserving cellular function. The effects of (R)-nicotine, diosmetin, their combined administration, and galantamine on heterogeneous BV2 transcriptional states have not been compared at single-cell resolution. METHODS: LPS-stimulated BV2 microglial-like cells were treated with (R)-nicotine, diosmetin, their combination (DR), or galantamine. Single-cell RNA sequencing was performed with three biological replicates per group and integrated with RNA velocity and SCENIC regulon inference to characterize treatment-associated state redistribution, inferred local transcriptional directionality and regulon-activity patterns. Functional validation included CCK-8 metabolic activity assays, multiplex cytokine ELISA, BDNF/GDNF quantification, qPCR, and high-content immunofluorescence analysis of iNOS and Arg1 at single-cell resolution. RESULTS: LPS decreased the relative abundance of the Itgae+/Plk4+ cluster while increasing the Nmur1+/Limk2+ cluster and inflammatory effector programs. DR treatment suppressed pro-inflammatory cytokine release without significantly reducing CCK-8-assessed metabolic activity, increased the Itgae+/Plk4+ cluster proportion, and increased BDNF/GDNF relative to LPS. RNA velocity and SCENIC analyses suggested that DR and galantamine showed distinct transcriptional and regulatory patterns: DR attenuated Batf-associated inflammatory regulons and was associated with increased Atf3-linked stress-response activity, whereas galantamine preferentially engaged DNA repair and genome-maintenance programs. CONCLUSION: These findings indicate that the DR condition was associated with remodeling of LPS-challenged BV2 microglial-like states, attenuation of inflammatory programs, and increased neurotrophic outputs relative to LPS, without significantly reducing CCK-8-assessed metabolic activity. This study provides a single-cell characterization of distinct treatment-associated responses to (R)-nicotine, diosmetin, their combined administration, and galantamine.

Microglia

[Conditioned reflex reproduction of evoked potentials during reinforcement by electrostimulation of the hypothalamus].

Conditioned evoked potentials to stimulation of a limb, a light flash or a short tone were studied on rats in acute experiments with nembutal anaesthesia and in chronic experiments. Electrical stimulation of the hypothalamus was used as reinforcement. Following the pairings of conditioned and hypothalamic stimulation, the appearance of conditioned EP was recorded, as manifest in the period of the previously applied unconditioned signal after its omission. Their emergence was facilitated after high-frequency stimulation of the hypothalamus or administration of galantamine, an anticholinesteraze drug. Coagulation of the hypothalamus did not prevent any manifestation of conditioned evoked potentials.

Animals

[Comparison of 2-aminopyridine, 3-aminopyridine and 4-aminopyridine hydrochlorides and iodomethylates by the degree of decrease in curare toxicity].

The authors carried out studies on rats with apnoea, indiced by (+)-tubucurarine and found protective action, due to galantamine, neostigmine, hydrochlorides and jodometilates of 2-aminopyridine, 3-aminopyridine and 4-aminopyridine. Jodmethylates had protective action in larger doses in comparison with the respective hydrochlorides of nonsubstituted pyridilamines. The authors proposed a method for determination and comparison of the effect of compounds, eliminating the action of antidepolarizating myorelaxants, on tubocurarine toxicity.

Aminopyridines

Galanthamine.

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Behavior

A chromosome-level genome assembly of Lycoris radiata reveals the evolutionary origin of Amaryllidaceae alkaloids and elucidates the complete galanthamine biosynthetic pathway.

Amaryllidaceae alkaloids (AmAs) comprise a structurally diverse group of specialized metabolites produced almost exclusively by species of the Amaryllidoideae subfamily and are of substantial pharmacological importance. However, the limited availability of high-quality genomes from Amaryllidoideae plants has constrained systematic investigations of the genes and evolutionary processes underlying AmA biosynthesis. Here, we present a chromosome-level genome assembly of Lycoris radiata, which enabled the discovery of key downstream enzymes in the galanthamine biosynthetic pathway and uncovered reversible reactions between two critical metabolite pairs. These findings provide new mechanistic insight into pathway architecture and enable reconstruction of the galanthamine biosynthetic pathway in Yarrowia lipolytica. Comparative genomic analyses indicate that several core genes for AmA biosynthesis originated in ancestral angiosperms, whereas the complete pathway was likely assembled in the Amaryllidoideae subfamily through gene duplication and neofunctionalization. Furthermore, integrated metabolomic and transcriptomic analyses suggest that roots contribute actively to AmA metabolism in Lycoris. Together, these findings provide a genomic and biochemical framework for understanding the evolution and engineering of AmA biosynthesis.

Lycoris

Postoperative apnoea following nivalin administration.

Four patients developed postoperative apnoea after neuroleptanalgesia, and were given Nivalin whilst in an apnoeic state to reverse residual neuromuscular block. Neuromuscular transmission was monitored by a peripheral nerve stimulator, and recurarization was not observed. Central respiratory depression was the cause of postoperative apnoea. The possible mechanisms and the mode of prevention are stated in this paper.

Adult

[Interaction of reversible inhibitors with the catalytic centers and allosteric sites of cholinesterases].

The kinetics of inhibition of the human red blood cell cholinesterase with galanthamine tacrine and oxazyl (ambenonium) and the effect of these drugs on chick, mouse, cat and rat blood plasma enzyme activity was studied. Galanthamine proved to bind with acetylcholinesterase in the anionic areas of the catalytic centres, oxazyl interacted in the area of the allosteric anionic site, and tacrin interacted with the hydrophobic areas of the enzyme.

Allosteric Site

[Electroencephalographic analysis of the central action of pyrazidol].

Pyrasidol (1,10-trimethylene-8-methyl-1,2,3,4-tetrahydropyrasino/1,2-q/indol hydrochloride) produces an activating influence on the EEG of the brain cortex, the reticular formation of the mesencephalon and hippocampus. It potentiates the electroencephalographic effects of amphetamine, 1-DOPA and 5-oxytryptophan, displays no central cholinolytic activity and has no influence on the electrophysiological effects of anticholinesterase and cholinomimetic agents.

5-Hydroxytryptophan

[Effect of reversible inhibitors on the thermal denaturation of cholinesterases].

The capacity of reversible inhibitors--galanthamine and tacrine--to protect the cholinesterase of rat and mouse brain from the thermal denaturation with the action of the temperature of 56 and 58 degrees C was revealed. The protective action was also noted when the reversible inhibitors decreased the activity of the enzyme. It appeared that with galanthamine the cholinesterase resistance to the thermal action was greater than with the action of tacrine.

Acridines