Design of Diarylheptanoid Derivatives as Dual Inhibitors Against Class IIa Histone Deacetylase and β-amyloid Aggregation

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with multiple etiologies. Beta-amyloid (Aβ) self-aggregation and overexpression of class IIa histone deacetylases (HDACs) are strongly implicated with AD pathogenesis. In this study, a series of novel diarylheptanoid derivatives were designed, synthesized and evaluated for use as dual Aβ self-aggregation and class IIa HDAC inhibitors. Among these compounds, 4j, 5c, and 5e displayed effective inhibitions for Aβ self-aggregation, HDAC5 activity and HDAC7 activity with IC50 values of <10 μM. The compounds contain three common features: (1) a catechol or pyrogallol moiety, (2) a carbonyl linker and (3) an aromatic ring that can function as an HDAC cap and create hydrophobic interactions with Aβ1-42. Furthermore, compounds 4j, 5c, and 5e showed no significant cytotoxicity to human neuroblastoma SH-SY5Y cells and also exhibited neuroprotective effect against H2O2-induced toxicity. Overall, these promising in vitro data highlighted compounds 4j, 5c, and 5e as lead compounds that are worthy for further investigation

護生綜合 實習前後護理能力分析

The purpose of the study is to analyze the senior nursing students’ clinical competence pre-and post-clinical practice and its relationship with clinical settings. Yu’squestionnaire, the Scale of Nursing Competence, was adopted for data collection and was self-administered by 898 senior students (4 th to 5 th year).A total of 798 pre test and 689 post test questionnaire were returned. The results showed:( 1) The students’ overall competence ranked between “competent” and “somewhat competent” both pre-and post- clinical practice. (2) Among the six sub- scales, interpersonal relationship (IPR) / communication was the highest and the critical care the lowest on both pre and post tests. (3) After practice, all students had higher clinical competence score with statistical significance in overall competence, planning/evaluation, teaching/ collaboration, IPR/communication, leadership and professional development. (4)The students’ practice in medical centers showed improvement in teaching/collab oration and IPR/communication. In regional hospitals there was improvement in overall nursing professional competence , planning/evaluation, teaching/collaboration, IPR/ communication and leadership. Students who rotated between hospitals showed improvement in overall competence and in all sub-scales except critical care. (5) Except for leadership competence, there were no significant relationship between the competence improvement and the clinical setting