International Journal of Cancer
December 2, 2010
Paul T. Henderson, Tao Li, Miaoling He et al.
37 citations
Platinum-based drugs like carboplatin kill cancer cells by forming DNA adducts, but measuring these adducts in tumors has been technically difficult. Using ultrasensitive accelerator mass spectrometry, researchers detected carboplatin-DNA monoadducts—precursors to toxic crosslinks—at extremely low levels in six cancer cell lines. The most drug-resistant cells had the fewest monoadducts at all time points over 24 hours. Importantly, microdoses (1/100th the therapeutic concentration) produced nearly identical adduct formation and repair kinetics as full doses, suggesting microdosing could predict treatment effects. Intracellular inactivation and efficient DNA repair, particularly nucleotide excision repair, significantly suppressed monoadduct formation in resistant cells, pointing to mechanisms of chemoresistance.
CNS Neuroscience & Therapeutics
January 10, 2023
Jing Wang, Min Liang, Qing Shang et al.
23 citations
Psilocin, the active metabolite of psilocybin, counteracts methamphetamine (METH)-induced hyperactivity and blocks the formation of conditioned place preference (CPP) in mice, indicating it may reduce the rewarding effects of METH. In an acute model, 1 mg/kg psilocin reduced the elevated activity caused by 2 mg/kg METH. In the CPP model, the same dose of psilocin prevented the development of place preference during acquisition but did not affect extinction or relapse. Molecular analysis revealed that psilocin's effects involve altered expression of dopamine 2 receptor (D2R) and phosphorylated ERK in the prefrontal cortex, nucleus accumbens, and ventral tegmental area. Inhibitors of D2R and ERK phosphorylation also blocked METH-induced hyperactivity and CPP acquisition, suggesting psilocin acts through D2R-mediated regulation of ERK phosphorylation.
Talanta
April 1, 2023
Chun-Hui Song, Wei Jia, Cui-Mei Liu et al.
14 citations
For the first time, identification and quantification of trace levels of new psychoactive substances (NPS) in chocolate have been achieved. Eleven NPS were detected in 65 seized chocolate samples, including deoxymethoxetamine, 3-OH-PCP, 6-APB, 4-APB, 4-OH-MiPT, 3-FEA, 2-FEA, 3-MMC, bromazolam, 2-FDCK, and ADB-BUTINACA. A general 1H quantitative NMR method was developed for 297 types of NPS, with limits of detection of 0.05-0.1 mg/mL, limits of quantification of 0.01-0.03 mg/mL, repeatability and reproducibility below 0.5% and 3.6%, and recoveries of 91.7% to 104.4%. Quantitative analysis showed NPS content ranged from 0.5 mg/g to 44.1 mg/g. The method is simple, fast, precise, and requires no reference materials. The random type and content of NPS pose significant health risks to consumers, warranting increased monitoring.
Neuropharmacology
December 15, 2024
Canyu Yang, Tahir Ali, Axiang Li et al.
11 citations
In a mouse model of depression induced by corticosterone, ketamine reversed depression-like behaviors and restored disrupted synaptic signaling, including the TrkB/BDNF and eIF4E/MNK1/p-eIF2α/ubiquitin pathways. Blocking eIF4E/MNK1 signaling with eFT508 prevented ketamine's antidepressant effects, but these were restored by 7,8-DHF, a BDNF/TrkB agonist. 7,8-DHF also increased eIF4E phosphorylation and MNK1 expression and enhanced p-eIF2α levels. Ketamine appears to act through the eIF4E/BDNF signaling pathway in the hippocampus, offering new insights into its molecular mechanism.
Fa yi xue za zhi
April 25, 2025
Yu-Meng Zuo, Wei Han, Jian-Bo Zhang et al.
Ketamine, a dissociative anesthetic used clinically for surgical anesthesia, can cause nerve damage, adverse emotional reactions, and other toxic side effects when abused. Its primary mechanism blocks N-methyl-D-aspartate receptors (NMDAR), but it also acts through multiple other pathways including AMPAR, opioid receptors, GABA receptors, monoaminergic receptors, cholinergic receptors, HCN channels, voltage-gated sodium channels, and L-type voltage-dependent calcium channels. This review summarizes the molecular mechanisms and toxic effects of ketamine to support forensic applications such as identifying symptomatic phenotypes of ketamine toxicity and detecting ketamine abuse.