Ai-Lin Liu completed her PhD in 2009 from the University of Macau. She has engaged in anti-AD drug discovery and mechanism researh, anti-influenza drug discovery and mechanism research, drug informatics and computational pharmacology for more than 10 years. She has published more than 50 papers in the international reputed journals, applied more than 10 patents and obtained 4 prizes for her outstanding scientific research.
Alzheimer’s disease (AD) treatment is a worldwide difficult problem, since the therapeutic effect of the present anti-AD drugs are not very ideal, and the development of new drugs is still facing various dificulties. DL0410, which is a candidate drug targeting multi-target, is undergoing a systematic preclinical studies, incluing pilot-scale synthesis, crystal polymorphism and bioavailability evaluation, preparation formulation, quality control, stability studies, pharmadynamics, action mechanisms, pharmacokinetics and safety evaluation. Compared with the clinical first-line anti-AD drugs, such as Donepezil and Rivastigmine, its advantages lie in the following aspects. Firstly, DL0410 displays stronger efficacy, and possesses polypharmacology features. It can regulate not only the balance of cholinesterases, improve the function of cholinergic system, but also acetylcholine mediated ion channel receptor α7nAChR. Meanwhile, it can not only block a lot of neuropathies caused by various pathogenic factors including Aβ aggregation, oxidation stress and inflammatory factors, but also increase the long term potential to improve the ability of memory and learning. The studies to explain these bioactivities and reveal their relationship will be performed in the future. Secongdly, DL0410 is very safe. The acute toxic effect of oral administration in mice showed its LD50 as 977 mg/kg, while its optimal effective dose is around 3~10 mg/kg, so its therapy index is more than 97.7. Thirdly, DL0410 without choral atom is easily synthesized and cheap. It can be widely used in clinic after the approval for AD treatment. In conclusion, DL0410 is a promising candidate for the future AD treatment.
Minyoung Lee has completed his PhD at the age of 34 years from college of medicine, Kyunghee University. Shee is the senior researcher of Korea institue of Radiological and medical sciences. She has published more than 25 papers in reputed journals until 2000.
Treatments of cancer try to destroy the entire tumor, but this tends to require lethal compounds and high doses of radiation. Recently, considerable attention has focused on therapy-induced senescence (TIS), which can be induced in tumor cells by low doses of therapeutic drugs or radiation, and provides a barrier to cancer development. However, the molecular mechanisms governing TIS remain unclear. Special attention has been paid to the potential anti-cancer effect of aspirin against human colorectal cancer (CRC). In this study, we investigated the effects of aspirin on TIS of CRC cells, and show that it occurs via sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK), two key regulators of cellular energy metabolism. Aspirin increased the senescence of CRC cells, increased the protein levels of SIRT1, phospho-AMPK (T172), and phospho-acetyl CoA carboxylase (S79), and reduced the cellular level of ATP. SiRNA-mediated down-regulation or pharmacological inhibition of SIRT1 or AMPK considerably reduced the aspirin-induced cellular senescence in CRC cells. In contrast, treatment with a SIRT1 agonist or an AMP analog (AICAR) induced cellular senescence. Remarkably, knockdown of SIRT1 abolished the aspirin-induced activation of AMPK, and vice versa. During the progress of aspirin-induced cellular senescence in CRC cells, SIRT1 showed increased deacetylase activity at an early time point, but was characterized by decreased activity with increased cytoplasmic localization at a later time point. Taken together, these results suggest that aspirin could provide anti-cancer effects by inducing senescence in CRC cells through the reciprocal regulation of SIRT1-AMPK signaling pathways.