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Identification and characterization of etomidate and metomidate metabolites in zebrafish, HLMs and S9 fraction by quadrupole-orbitrap LC-MS/MS for drug control.
J Chromatogr B Analyt Technol Biomed Life Sci
January 2025
Food and Drug Anti-doping Laboratory, China Anti-doping Agency, 1st Anding Road, Chaoyang District, 100029 Beijing, China. Electronic address:
Etomidate is a common non-barbiturate anesthetic with psychoactivity, and metomidate, a structural modifier of etomidate, also has the same psychoactive effect, and the abuse of both has gradually intensified. In this study, etomidate, metomidate and their metabolic profiles with 4 days postfertilization (4dpf) zebrafish, 4 months postfertilization (4mpf) zebrafish, human liver microsomes (HLMs) and human liver S9 fraction were investigated using Liquid chromatography with high resolution mass spectrometry (LC-HRMS) for the first time. 14 etomidate metabolites and 11 metomidate metabolites were found, and the related metabolic pathways included monohydroxylation, dihydroxylation, dehydrogenation, N-dealkylation, O-dealkylation, oxidation, N-glucuronidation, O-glucuronidation and combination.
View Article and Find Full Text PDFMechanism of action of the Banxia-Xiakucao herb pair in sleep deprivation: New comprehensive evidence from network pharmacology, transcriptomics and molecular biology experiments.
J Ethnopharmacol
November 2024
Sleep Medicine Center, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China. Electronic address:
Article Synopsis
- Chinese herb pairs, like Banxia-Xiakucao (BXHP), are important in traditional Chinese medicine and help treat health problems with few side effects, especially insomnia.
- This study looked at how BXHP works to help with sleep issues using different scientific methods like testing on rats and studying the ingredients.
- The results showed that BXHP helps people sleep better, reduces anxiety, and balances certain hormones and chemicals in the body.
-Hydroxypiridinedione: A Privileged Heterocycle for Targeting the HBV RNase H.
Molecules
June 2024
Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece.
Hepatitis B virus (HBV) remains a global health threat. Ribonuclease H (RNase H), part of the virus polymerase protein, cleaves the pgRNA template during viral genome replication. Inhibition of RNase H activity prevents (+) DNA strand synthesis and results in the accumulation of non-functional genomes, terminating the viral replication cycle.
View Article and Find Full Text PDFApplicability of a Chemiluminescence Immunoassay to Screen Postmortem Bile Specimens and Its Agreement with Confirmation Analysis.
Int J Mol Sci
March 2024
Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Via dell'Istria 65/1, 34137 Trieste, Italy.
Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children. Toxicological investigation consists in screening and, subsequently, confirming the result with specific techniques, such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). As there is no screening test on the market to test postmortem bile specimens, the novelty of this study was in investigating the applicability of a chemiluminescence immunoassay, designed for other matrices and available on the market, on bile and validate its use, testing the agreement with LC-MS/MS analysis.
View Article and Find Full Text PDFIdentification and Biological Evaluation of a Novel Small-Molecule Inhibitor of Ricin Toxin.
Molecules
March 2024
Department of Operational Medicine, Institute of Environmental and Operational Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Tianjin 300050, China.
Article Synopsis
- Ricin, a toxic plant-derived protein, primarily causes harm through its ricin toxin A chain (RTA), which is a target for drug development since effective antidotes are currently lacking.
- Recent research identified a compound named RSMI-29 that interacts with both key binding sites on RTA, showing promise in blocking RTA's harmful effects on protein synthesis and cell viability.
- In experimental models, RSMI-29 significantly mitigated ricin’s toxic impact in various organs and exhibited favorable drug-like characteristics, suggesting it as a potential treatment for ricin-related poisoning.
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