Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study.

Objective: Inflammatory cytokines disturbance is the main result of immune dysregulation, which is widely described in major depressive disorder (MDD). However, the potential causal relationship between these two factors has not been discovered. Therefore, the purpose of this study was to investigate the causal relationship between inflammatory cytokines and MDD risk by using the two-sample Mendelian randomization (MR) analysis. Method: Two genetic instruments obtained from publicly available gene profile data were utilized for the analysis. We obtained the genetic variation data of 41 inflammatory cytokines from genome-wide association studies (GWAS) meta-analysis of 8293 individuals of Finnish descent. The MDD data, including 135,458 MDD cases and 344,901 controls, were obtained from the Psychiatric Genomics Consortium Database. For the Mendelian randomization (MR) estimation, several methods were employed, namely, MR-Egger regression, inverse-variance weighted (IVW), weighted median, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods. Result: A causal relationship was identified between the genetically proxied levels of Interleukin (IL) -18, IL-1ß, and Regulated upon activation normal T cell expressed and secreted (RANTES) and the risk of MDD (OR = 0.968, 95%CI = 0.938, 0.998, p = 0.036; OR = 0.875, 95%CI = 0.787, 0.971, p = 0.012; OR = 0.947, 95%CI = 0.902, 0.995, p = 0.03; respectively). However, our Mendelian randomization (MR) estimates provided no causality of MDD on inflammatory cytokines. Conclusion: Our study elucidates the connection between inflammatory cytokines and MDD by using MR analysis, thereby enhancing our comprehension of the potential mechanisms. By identifying these associations, our findings hold substantial implications for the development of more effective treatments aimed at improving patient outcomes. However, further investigation is required to fully comprehend the exact biological mechanisms involved.

Efficacy of Smart Speaker-Based Metamemory Training in Older Adults: Case-Control Cohort Study.

BACKGROUND: Metamemory training (MMT) is a useful training strategy for improving cognitive functioning in the older adult population. Despite the advantages, there are limitations imposed by location and time constraints. OBJECTIVE: This study aimed to develop a smart speaker-based MMT program and evaluate the efficacy of the program in older adults without cognitive impairment. METHODS: This study used a case-control cohort design. The smart speaker-based MMT program comprised 3 training sessions per day, 5 days a week, for 8 weeks. Each training session took approximately 15 minutes. This program was implemented using smart speakers, not human trainers. All participants completed the Mini-Mental State Examination, Subjective Memory Complaints Questionnaire, Verbal Learning Test, Digit Span Test, fluency tests, and a short-form version of the Geriatric Depression Scale before and after training. RESULTS: A total of 60 subjects (29 in the MMT group and 31 in the control group) participated in the study. The training group showed significant increases in the delayed free recall, digit span forward, digit span backward, and fluency test scores compared with the control group. CONCLUSIONS: This study confirmed the efficacy of smart speaker-based MMT in older adults. Home-based smart speaker-based MMT is not limited with respect to location or constrained by space and may help older adults with subjective cognitive decline without requiring intervention by human professionals.

Synthesis and SAR of bis-statine based peptides as BACE 1 inhibitors.

A new series of bis-statine based peptidomimetic inhibitors of human beta-secretase (BACE 1) was developed by structure-based modification of the three regions to the initial lead 3: an N-terminus, a central bis-statine core, and a C-terminus. Introduction of a 4-aminomethylbenzoic acid on the C-terminus resulted in a potent BACE 1 inhibitor with an IC50 value of 21 nM. The general requirements for the optimal substrate-enzyme interaction are disclosed herein.