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.
BMC Complementary Medicine and Therapies
March 16, 2026
Xing-Chen Zhou, Shuang Wu, Kai-Zheng Wang et al.
Patients with lumbar disc herniation (LDH) who also have negative emotions show altered brain functional connectivity in networks involved in self-referential thought, executive control, and salience processing. Lever positioning manipulation (LPM) treatment relieved anxiety in these patients and was associated with changes in brain activation and connectivity, particularly between the orbitofrontal cortex and the rectal gyrus. Changes in functional connectivity in these regions correlated positively with reductions in anxiety scores, suggesting that neural remodeling of the ventral attention and default mode networks may underlie the anxiety relief seen with LPM.
Journal of Affective Disorders
June 15, 2025
Guangzheng Tang, Bijun Chen, Manhua Wu et al.
Mindfulness-based cognitive therapy (MBCT) reduced worry severity more than online psychoeducation in people with generalized anxiety disorder, but both interventions reduced anxiety to a similar degree overall. Among those who experienced childhood emotional abuse, MBCT was more effective at reducing anxiety than psychoeducation, and also more effective for anxiety in that subgroup compared to those without such abuse. The findings suggest MBCT's effect on anxiety depends on a history of childhood maltreatment, especially emotional abuse.
Zoological Research
November 18, 2022
Rongjun Ni, Tianhao Gao, Yi-Yan Wang et al.
Chronic lithium exposure reduces mania-like behavior and c-Fos expression in the medial prefrontal cortex of adult male mice treated with ketamine. Transcriptome sequencing of the prefrontal cortex shows that lithium inactivates the PI3K-AKT signaling pathway. Inhibiting AKT signaling with MK2206 or knocking down AKT in the mPFC reverses ketamine-induced mania, while activating AKT with SC79 promotes mania in low-dose ketamine-treated mice. Inhibiting PI3K with LY294002 also reverses mania, but inhibiting mTOR with rapamycin has no effect. Lithium may therefore ameliorate ketamine-induced mania via the PI3K-AKT pathway, suggesting a novel target for bipolar disorder treatment.
Translational Psychiatry
October 23, 2021
Fangfang Chen, Xueyu Lv, Jiliang Fang et al.
Body-mind relaxation meditation (BMRM) alters thalamocortical functional connectivity in medication-naive adolescents with major depressive disorder (MDD) and healthy controls. Before the intervention, MDD patients showed reduced connectivity between the bilateral precuneus/posterior cingulate cortex and specific thalamus subregions, and increased connectivity between the left occipital thalamus and left medial frontal cortex. After BMRM, these aberrant connections normalized in MDD patients, and both groups showed decreased connectivity between the left rostral temporal thalamus and left inferior occipital region. These changes suggest BMRM may strengthen connections between the thalamus and default mode network, which support attention and self-related processes. The small sample size limits generalizability.
Pharmacology, Biochemistry and Behavior
January 12, 2021
Tianhao Gao, Rongjun Ni, Shasha Liu et al.
Pretreatment with lithium moderates the effects of a single dose of ketamine on mania-like behavior and c-Fos expression in the mouse forebrain. Ketamine increased movement and induced higher c-Fos expression in several forebrain regions, including the lateral septal nucleus, hypothalamus, amygdala, and hippocampus. Chronic lithium treatment attenuated the ketamine-induced increase in movement and inhibited the rise in c-Fos-immunoreactive neurons in the dentate gyrus, CA1, dorsal and ventral subiculum, and amygdaloid nuclei. These findings may help understand mania episodes related to ketamine treatment for major depressive disorder and bipolar disorder.