As human-origin cells, human dental pulp stem cells (hDPSCs) are thought to be potentially useful for biological and medical experiments. They are easily obtained from lost primary teeth or extracted wisdom teeth, and they are mesenchymal stem cells that are known to differentiate into osteoblasts, chondrocytes, and adipocytes. Although hDPSCs originate from neural crest cells, it is difficult to induce hDPSCs to differentiate into neuron-like cells. To facilitate their differentiation into neuron-like cells, we evaluated various differentiation conditions. Activation of K + channels is thought to regulate the intracellular Ca 2+ concentration, allowing for manipulation of the cell cycle to induce the differentiation of hDPSCs. Therefore, in addition to a conventional neural cell differentiation protocol, we activated K + channels in hDPSCs. Immunocyto­chemistry and real-time PCR revealed that applying a combination of 3 stimuli (high K + solution, epigenetic reprogramming solution, and neural differentiation solution) to hDPSCs increased their expression of neuronal markers, such as β3-tubulin, postsynaptic density protein 95, and nestin within 5 days, which led to their rapid differentiation into neuron-like cells. Our findings indicate that epigenetic reprogramming along with cell cycle regulation by stimulation with high K + accelerated the differentiation of hDPSCs into neuron-like cells. Therefore, hDPSCs can be used in various ways as neuron-like cells by manipulating their cell cycle.

Background and PurposeNeuropsychiatric symptoms in Parkinson's disease (PD) have been shown to significantly affect quality of life (QOL). We investigated the impact of safinamide on depression and apathy when administered as an adjunct to levodopa in Japanese patients with PD.MethodsThis was a post-hoc analysis of data from a phase 2/3 clinical study of safinamide in Japanese patients with PD experiencing wearing-off (JapicCTI-153056; https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-153056). Patients received placebo, safinamide 50 mg, or safinamide 100 mg as an adjunct therapy. The endpoints for this analysis were changes from baseline to Week 24 in the Unified Parkinson's Disease Rating Scale (UPDRS) Part I item 3 (depression) and item 4 (apathy) scores and the Parkinson's Disease Questionnaire (PDQ-39) “emotional well-being” domain score. Subgroup analyses investigated the relationship between neuropsychologic symptoms and improvements in motor fluctuation and assessed which patient populations might be expected to obtain neuropsychologic benefit from safinamide.ResultsCompared with placebo, safinamide (both doses) significantly improved UPDRS Part I item 3 scores in the overall analysis population, and the 100-mg dose improved UPDRS Part I item 4 scores in the population with apathy at baseline. Changes in the PDQ-39 “emotional well-being” score showed numerical, but not significant, dose-related improvements. Notable reductions in depression were associated with a change in daily ON-time ≥1 h, pain during OFF-time at baseline, and female sex.ConclusionsThe results from this post-hoc analysis of the Japanese phase 2/3 study suggest that safinamide could bring benefits to patients with PD who have mild depression, pain during the OFF phase. In addition, safinamide might provide particular benefits for patients with PD who have mild apathy and female.

The non-dopaminergic and dopaminergic actions of safinamide may alleviate pain in patients with Parkinson's disease (PD). We investigated the efficacy of safinamide for pain when administered as an adjunct to levodopa in Japanese patients with PD. Methods: This was a post hoc analysis of a phase 2/3 clinical study of safinamide in Japanese patients with PD who were experiencing wearing-off. Pain was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) Part II 'sensory symptoms' item 17, on a scale of 0-4, and the 39-item Parkinson's Disease Questionnaire (PDQ-39) 'bodily discomfort' domain score. Subgroup analyses, according to baseline symptoms and concomitant medications, were also performed. Results: Least square (LS) mean changes in the UPDRS item 17 score from baseline to Week 24 in the placebo, safinamide 50-mg and safinamide 100-mg groups during the OFF phase were 0.08, − 0.15 (p = 0.0133 vs placebo) and − 0.18 (p = 0.0054), respectively, and during the ON phase were 0.04, − 0.08 (p = 0.0529) and − 0.08 (p = 0.0505), respectively. Changes from baseline to Week 24 in PDQ-39 'bodily discomfort' scores were not significantly different in safinamide groups vs placebo. The presence of moderate-to-severe bradykinesia or earlymorning dystonia at baseline resulted in numerically greater effect sizes in UPDRS item 17 scores during the OFF phase. Conclusions: Safinamide 50 mg and 100 mg reduced the UPDRS item 17 score in patients with PD, especially during the OFF phase. Patients with moderate-to-severe bradykinesia and early-morning dystonia may benefit from safinamide treatment.

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Introduction In the treatment of insomnia, both subjective and objective evaluations are essential. The orexin receptor antagonist, lemborexant, has a favorable profile in terms of efficacy, acceptability, and tolerability for adults diagnosed with insomnia. To date, the long-term efficacy of lemborexant has been evaluated solely on a subjective basis, with no long-term objective measures under natural sleeping conditions. Therefore, a small, lightweight sleep electroencephalograph monitor was used to evaluate sleep objectively at home after 4 and 12 weeks of lemborexant treatment. Methods Adults and elderly subjects with insomnia disorder per DSM-5 were enrolled in an open-label, single-arm, single-center trial. Participants took lemborexant (5/10 mg) at bedtime for 12 weeks. In addition, they underwent a home-based sleep study at baseline and weeks 4 and 12. Sleep ­efficiency (SE), total sleep time (TST), latency to persistent sleep (LPS), and wake after sleep onset (WASO) were ­evaluated at home. Sleep disturbance (Pittsburgh sleep quality index: PSQI), ­sleepiness (Epworth sleepiness scale: ESS), and depressive symptoms (Beck depression index: BDI) were examined. Results 31 subjects completed the 4-week and 29 completed the 12-week assessments. Subjects showed significant improvements in objective SE at weeks 4 and 12 of treatment compared to untreated baseline. Objective TST tended to increase with the treatment at week 12. Mixed-effects linear analysis revealed that the poorer the sleep measures (SE, TST, LPS, and WASO) were at baseline, the more these measures improved with lemborexant. Scores of PSQI, ESS, and BDI significantly decreased (improved) with lemborexant treatment compared to those at baseline. Conclusion The findings from the analyses demonstrate objective improvement of SE with lemborexant treatment across 12 weeks and support the previously reported benefit of lemborexant using polysomnography. Support (if any)