Discovery of substituted (4-phenyl-1H-imidazol-2-yl)methanamine as potent somatostatin receptor 3 agonists.

We report SAR studies on a novel non-peptidic somatostatin receptor 3 (SSTR3) agonist lead series derived from (4-phenyl-1H-imidazol-2-yl)methanamine. This effort led to the discovery of a highly potent low molecular weight SSTR3 agonist 5c (EC50=5.2 nM, MW=359). The results from molecular overlays of 5c onto the L-129 structure indicate good alignment, and two main differences of the proposed overlays of the antagonist MK-4256 onto the conformation of 5c lead to inversion of antagonism to agonism.

Coix lacryma-jobi Seed Oil Reduces Fat Accumulation in Nonalcoholic Fatty Liver Disease by Inhibiting the Activation of the p-AMPK/SePP1/apoER2 Pathway.

The lipid metabolism disorder is the key role of Nonalcoholic fatty liver disease (NAFLD). Selenoprotein P plays an important role in the pathological process of lipid accumulation. Coix lacryma-jboi seed oil (CLSO) is an active component extracted from Coix lacryma-jobi seed (CLS) which has been found to be effective of reducing blood fat and antioxidative. But the effect and mechanism of CLSO on NAFLD are not clear. The aim of this study was to explore the therapeutic effect and mechanism of CLSO in the treatment of NAFLD. Our result showed that CLSO decreased the liver/body weight ratio, lowered the total cholesterol (TC) and triacylglycerol (TG), and elevated the high density lipoprotein (HDL) in serum. CLSO reduced the lipid deposition in the liver of NAFLD rats. In addition, CLSO could bring down the abnormal expression of superoxide dismutase (SOD) and malondialdehyde (MDA). Moreover, CLSO significantly declined the liver apolipoprotein E (apoE), apolipoprotein E receptor (apoER) and selenoprotein P 1 (SePP1) expression. In vivo, CLSO decreased the lipid droplets and TG level, reduced the protein expression of SePP1, apoER, phosphor-adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) in the cytoplasm of HepG2 cells induced by oleic acid and palmitic acid (OP). At the same time, lipid accumulation was observed in the Sepp1 high expression cells induced by endoplasmic reticulum (ER) activator tunicamycin (Tm). CLSO could identically reduce the protein expression of SePP1, apoER, p-AMPK in the cytoplasm of HepG2 cells induced by Tm. This result not only proved the CLSO had therapeutic effect on NAFLD, but also confirmed its mechanism associated with degrading the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) which led to the decrease of the expression SePP1/apoER2 in order to reduce lipid accumulation. The study suggests CLSO has great medicinal value in treating NAFLD besides its edibility.

The top 100 most cited scientific reports focused on diabetes research.

AIMS: The number of citations that a paper has received reflects the impact of the article within a particular medical research area. However, which articles are cited most frequently in diabetes research is unknown. We aimed to identify the most frequently cited 100 articles that describe advances focused on diabetes research. METHODS: Science Citation Index Expanded database was used to determine the 100 most cited articles in diabetes research. The key characteristics of the top 100 cited articles, including citation ranking, year of publication, publishing journal, type of study, h-index, PMC citation, patent citation, country of origin, funding source, and authorship, were analyzed. RESULTS: The number of citations ranged from 10292 to 1121. The 100 most cited articles were published between 1962 and 2010. New England Journal of Medicine published the largest number of the most cited articles (n = 23), followed by Diabetes Care (n = 14) and Nature (n = 12). The greatest number of contributions came from the USA, followed by the UK and Canada. RCT was the most popular article type, followed by basic science studies and observational studies. There was a positive correlation between total citations and h-indexes and PMC citations, while there was no correlation with patent citations. CONCLUSIONS: The most influential report in diabetes research seems to be RCT, which is performed to confirm the effectiveness and outcome of anti-diabetes drugs in patients with diabetes. This study presents insight into the historical development of diabetes research, and provides foundations for further investigations.

Growing Trend of China's Contribution to Global Diabetes Research: A Systematic Literature Review.

China, as a rapidly developing country with the largest population in the world, is playing an increasingly important role in diabetes research. There are >10,000 diabetes doctors who care for a large population of diabetic patients. The quantity and quality of research on diabetes from 3 major regions of China, including Mainland China (ML), Taiwan (TW), and Hong Kong (HK), is unknown. We aimed to analyze the contributions of each of these 3 regions to diabetes research.Articles on diabetes originating from ML, TW, and HK that were published from 2005 to 2014 were retrieved from the Web of Science. The quantity of articles, citations, article types, and articles published in high-impact journals were analyzed.A total of 9302 articles were retrieved from the 3 regions of China. There were 6775 from ML, 1993 from TW, and 534 from HK, with an increasing trend in publications from 2005 to 2014. After 2006, the number of publications from ML exceeded TW and HK. The largest total number of citations (48,296) was from ML. The highest mean citations, however, were from HK (15.90). PLoS One was the most popular journal in all 3 regions. The greatest number of RCTs, clinical trials, meta-analyses, and articles published in high-impact journals were from ML.There has been a significant increase in the number of articles published on diabetes research from China during the past 10 years. Most of the articles were published by authors in ML, and an increasing trend began in 2006. HK had the highest quality research output in terms of mean citations per article.