The impacts of natural product miltirone and the CYP2D6 pharmacogenetic phenotype on fluoxetine metabolism.

Introduction: To study the effects of drug-induced CYP2D6 activity inhibition and genetic polymorphisms on fluoxetine metabolism, rat liver microsomes (RLMs) and SD rats were used to investigate the potential drug‒drug interactions (DDIs), and CYP2D6 http://muchong.com/t-10728934-1 recombinant baculosomes were prepared and subjected to catalytic reactivity studies. Methods and Results: All analytes were detected by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS). After screening for 27 targeted natural products, miltirone was identified as having obvious inhibitory effect on fluoxetine metabolism in RLMs. In vivo, the concentration of fluoxetine in rat blood increased markedly after miltirone administration. The molecular docking results showed that miltirone bound more strongly to CYP2D6 than fluoxetine, and PHE120 may be the key residue leading to the inhibition of CYP2D6-mediated fluoxetine N-demethylation by miltirone. In terms of the genetic polymorphism of CYP2D6 on fluoxetine metabolism, the intrinsic clearance values of most variants were significantly altered. Among these variants, CYP2D6*92 and CYP2D6*96/Q424X were found to be catalytically inactive for fluoxetine metabolism, five variants (CYP2D6*89/L142S, *97/F457L, *R497, *V342M and *R344Q) exhibited markedly increased clearance values (>125.07%) and seven variants (CYP2D6*2, *10, *87/A5V, *93/T249P, *E215K, *R25Q and *R440C) exhibited significantly decreased clearance values (from 6.62% to 66.79%) compared to those of the wild-type. Conclusion: Our results suggest that more attention should be given to subjects in the clinic who take fluoxetine and also carry one of these infrequent CYP2D6 alleles or are coadministered drugs containing miltirone.

Can Priming Multiple Identities Enhance Divergent Thinking for Middle School Students?

Previous studies have found that promoting multiple identities can improve children's creative performance (divergent thinking). The present study employed a priming paradigm to design two experiments and investigate whether promoting a sense of multiple identities in middle school students could enhance their divergent thinking, a key component of creativity. In Experiment 1, 77 junior high school students were divided into multiple identities and physical trait condition groups. They were instructed to think about a child with multiple identities or physical traits. The results showed that there were no differences in divergent thinking (DT) scores between the two groups. In Experiment 2, we modified the priming method by asking participants to think about and write a description of the various identities or physical traits and employed a subjective top-scoring method to make up for shortcomings in the traditional scoring method when applied to originality. The results still showed no significant difference in scores between the identity and physical trait groups. Thus, the results of this study contradict those of previous research, which found that the identity group demonstrated significantly higher scores on a creativity test than did those in the physical trait group. Several potential factors affect this outcome, but it seems that priming to enhance divergent thinking is not particularly effective. Thus, the social priming effect should be pursued with caution regarding both replicability and generalizability.

Impact of aerobic exercise on cognitive function in patients with schizophrenia during daily nursing: A protocol for systematic review and meta-analysis.

OBJECTIVES: To assess the effect of aerobic exercise (AE) on cognition function in people with schizophrenia (SZ) during daily nursing. METHODS: The literature search will be conducted via PubMed, Embase, Cochrane Library, and Web of Science. Weighted mean difference (WMD) or standardized mean difference (SMD) and 95% confidence intervals (CIs) will be adopted to calculate the association between AE and cognitive function in patients with SZ. Publication bias will be performed by Begg test. When there is publication bias, "cut-and-fill method" will be adopted to adjust publication bias. Sensitivity analysis will be used to test the stability of the result. When the heterogeneity is large (I2 ≥ 50%), meta regression will be used to explore the source of inter-study heterogeneity. When the heterogeneity is large (I2 ≥ 50%) and the results are statistically significant (P < .05), age, sex, duration of disease, duration of intervention, amount of exercise per week, improvement of cardiopulmonary health, and other factors will be sub-analyzed. CONCLUSION: This meta-analysis will evaluate the impact of aerobic exercise on cognitive function in patients with SZ during daily nursing on the basis of existing evidence. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/C8ABX.

Antipsychotics With Different Chemical Structures Cause Different Degrees of Functional Impairments in the Primary Visual Cortex in a Murine Model: A Pilot Study.

Background: Antipsychotic medications can impair vision in patients with schizophrenia. However, little is known regarding the pharmacodynamics of antipsychotics in the primary visual cortex. We aimed to study the pharmacodynamics of antipsychotics in the visual cortex in a murine model. Methods: We used an adapted 2-photon imaging technique to observe changes in calcium dynamics induced by 4 antipsychotics (olanzapine, risperidone, aripiprazole, and amisulpride) in the primary visual cortex of healthy and schizophrenic C57BL/6 mice. Visual function was further assessed by using a novel object recognition test. Results: All 4 antipsychotics decreased calcium activity in the primary visual cortex and reduced visual recognition test scores in healthy and schizophrenic mice. The most potent drug was olanzapine, followed by risperidone, aripiprazole, and amisulpride. All drugs showed significant differences between groups. Conclusion: Our pilot study demonstrated that antipsychotics impair visual cortical function. This finding underscores the importance of monitoring for visual adverse events in patients receiving antipsychotic medications to treat schizophrenia.

Association of CSF CD40 levels and synaptic degeneration across the Alzheimer's disease spectrum.

The CD40 pathway has been implicated in microglial activation, which is considered as a key factor in the pathogenesis of Alzheimer's disease (AD). However, the association of CSF CD40 and synaptic degeneration in living human is not clear. A total of 294 subjects with different severities of cognitive impairments were included in this study: 84 participants with normal cognition, 143 patients with mild cognitive impairment (MCI) and 67 patients with mild AD. Levels of CD40 in CSF were compared among the three groups. Further, several linear regression models were conducted to explore the associations of CSF CD40 and neurogranin levels (reflecting synaptic degeneration) when controlling for age, gender, educational attainment, APOE4 genotype, clinical diagnosis, CSF Aß42 and tau proteins. We found that CSF CD40 levels were significantly decreased in patients with mild AD compared with healthy controls and MCI patients (control vs. AD, p = 0.0026; MCI vs. AD, p = 0.0268). However, there were no significant differences in CSF CD40 levels between controls and patients with MCI (p = 0.37). In addition, CSF CD40 levels were associated with neurogranin in the pooled sample when controlling for age, gender, educational attainment, APOE4 genotype and diagnosis. In summary, our findings support the notion that the CD40 pathway may contribute to an important mechanism underlying synaptic degeneration in AD.