Discovery of a novel small molecule PT109 with multi-targeted effects against Alzheimer's disease in vitro and in vivo
EUROPEAN JOURNAL OF PHARMACOLOGY
Authors: Chen, Qiuhe; Tu, Yalin; Mak, Shinghung; Chen, Jingkao; Lu, Junfeng; Chen, Chen; Yang, Xiaohong; Wang, Shengnan; Wen, Shijun; Ma, Shanshan; Li, Mingtao; Han, Yifan; Tism, Karl Wah-Keung; Pi, Rongbiao
Abstract
Alzheimer's disease (AD), which is characterized by impairment of cognitive functions, is a chronic neurodegenerative disease that mainly affects the elderly. Currently available anti-AD drugs can only offer limited symptom-relieving effects. "One-compound-Multitargeted Strategy" have been recognized as the promising way to win the war against AD. Herein we report a potential anti-AD agent PT109 with multi-functions. First, an 81-kinase screening was carried out and results showed that PT109 potently inhibited c-Jun N-terminal kinases and Serum and glucocorticoid-inducible kinase 1, which are the important signaling molecules involved in neurogenesis, neuroprotection and neuro-inflammation and mildly inhibit glycogen synthase kinase-3 beta as well as protein kinase C gamma, both are involved in AD pathological processes. In addition, in vitro studies of immunofluorescent staining and Western blot showed that PT109 might promote the neurogenesis of C17.2 cells and induce synaptogenesis in primary cultured rat hippocampal neurons. We detected and confirmed the neuroprotective effect of PT109 in cultured HT22 cells by MTT assay, dehydrogenase assay, glutathione assay and reactive oxygen species assay. Furthermore, the results of Western blot, ELISA assay and immunofluorescent staining indicated that PT109 attenuated lipopolysaccharide-induced inflammation in BV2 cells and primary astrocytes. The results of Morris water maze and Step-through test indicated that PT109 improved the spatial learning ability in APP/PS1 mice. More importantly, the in vivo pharmacokinetic parameters indicated that PT109 had better medicinal properties. Taken together, our findings suggest that PT109 may be a promising candidate for treating AD through multiple targets although further studies are ought to be conducted.
Association between Facebook Use, Depression and Family Satisfaction: A Cross-Sectional Study of Romanian Youth
IRANIAN JOURNAL OF PUBLIC HEALTH
Authors: Iovu, Mihai-Bogdan; Runcan, Remus; Runcan, Patricia-Luciana; Andrioni, Felicia
Abstract
Background: In recent years, Facebook has increasingly become an essential part of the lives of people, particularly youths, thus many research efforts have been focused on investigating the potential connection between social networking and mental health issues. This study aimed to examine the relationship between Face book use, emotional state of depression, and family satisfaction. Methods: This study used the online survey created in Google Docs on the Facebook 'wall', as research method. The survey was available during Jun Jul2015 in Romania. In our cross-sectional study on a sample of 708 young Facebook users (aged 13-35), we divided the sample into 3 groups: ordinary, middle, and intense Face book users. Materials and instruments: the survey comprised a series of basic demographic as well as some measures of Facebook addiction, depression, and family satisfaction. We used two methods connected with extensive Facebook usage, the first one measuring only the intensity of use, and the second one measuring not only the intensity but also the consequences of this use. Results: Facebook engagement is negatively related to family satisfaction. Moreover, Facebook engagement is positively related to depression symptoms. The Pearson correlations showed that higher Facebook intensity is positively associated with Facebook addiction. Conclusion: The study confirm previously published findings of other authors in the fields of social networking psychology. The study examined the relationship between Facebook use, depression, and life satisfaction and the hypotheses were supported.