Discovery of potent α1L-adrenoceptor agonists: Design and synthesis of bicyclic derivatives.

We aimed to create a novel and potent α(1L)-adrenoceptor agonist because such agonists are possible drug candidates for stress urinary incontinence. We used ligand-based drug design and evaluated the α(1L)-adrenoceptor agonist activity of the designed compounds. Among them, tetrahydroquinoline derivative 50 showed the most potent activity (ratio of noradrenaline half maximal effective concentration, 0.0028) and effectively induced contraction of rat bladder neck.

Cyclic mechanical strain maintains Nanog expression through PI3K/Akt signaling in mouse embryonic stem cells.

Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17 Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling.

The Role of Food Antioxidants, Benefits of Functional Foods, and Influence of Feeding Habits on the Health of the Older Person: An Overview.

This overview was directed towards understanding the relationship of brain functions with dietary choices mainly by older humans. This included food color, flavor, and aroma, as they relate to dietary sufficiency or the association of antioxidants with neurodegenerative diseases such as dementia and Alzheimer's disease. Impairment of olfactory and gustatory function in relation to these diseases was also explored. The role of functional foods was considered as a potential treatment of dementia and Alzheimer's disease through inhibition of acetylcholinesterase as well as similar treatments based on herbs, spices and antioxidants therein. The importance of antioxidants for maintaining the physiological functions of liver, kidney, digestive system, and prevention of cardiovascular diseases and cancer has also been highlighted. Detailed discussion was focused on health promotion of the older person through the frequency and patterns of dietary intake, and a human ecology framework to estimate adverse risk factors for health. Finally, the role of the food industry, mass media, and apps were explored for today's new older person generation.