Elaiophylin reduces body weight and lowers glucose levels in obese mice by activating AMPK.

Obesity is an epidemic affecting 13% of the global population and increasing the risk of many chronic diseases. However, only several drugs are licensed for pharmacological intervention for the treatment of obesity. As a master regulator of metabolism, the therapeutic potential of AMPK is widely recognized and aggressively pursued for the treatment of metabolic diseases. We found that elaiophylin (Ela) rapidly activates AMPK in a panel of cancer-cell lines, as well as primary hepatocytes and adipocytes. Meanwhile, Ela inhibits the mTORC1 complex, turning on catabolism and turning off anabolism together with AMPK. In vitro and in vivo studies showed that Ela does not activate AMPK directly, instead, it increases cellular AMP/ATP and ADP/ATP ratios, leading to AMPK phosphorylation in a LKB1-dependent manner. AMPK activation induced by Ela caused changes in diverse metabolic genes, thereby promoting glucose consumption and fatty acid oxidation. Importantly, Ela activates AMPK in mouse liver and adipose tissue. As a consequence, it reduces body weight and blood glucose levels and improves glucose and insulin tolerance in both ob/ob and high-fat diet-induced obese mouse models. Our study has identified a novel AMPK activator as a candidate drug for the treatment of obesity and its associated chronic diseases.

[Diagnosis and treatment rule of traditional Chinese medicine for syndrome factors of chronic congestive heart failure: a study based on Shannon entropy method].

OBJECTIVE: The primary aim of this research is to systematically sort out and analyze available clinical documents for chronic congestive heart failure in traditional Chinese medicine (TCM) and integrated traditional Chinese and Western medicine, and to explore the diagnosis and treatment rule of TCM syndrome factors with data mining method. METHODS: Based on the China National Knowledge Internet (CNKI) and Chinese Biomedical Literature Database (CBM), using "chronic heart failure" or "chronic congestive heart failure" or "chronic cardiac insufficiency" and "traditional Chinese medicine" or "syndrome" or "integrated traditional Chinese and Western medicine" as keywords for literature selection, we used Shannon entropy nonlinear complex system method for the feature extraction after data preprocessing. RESULTS: The statistics showed that yang deficiency, qi deficiency, blood stasis, water retention, yin deficiency, and turbid phlegm were principal TCM syndrome factors; herbs of qi-tonifying, blood-activating, water-draining, phlegm-dispelling, exterior-releasing, interior-warming were main drugs for clinical application. The symptoms and Chinese herbs which intimately connect with TCM syndrome factors were extracted, while their diagnostic contribution degrees were quantified by correlation coefficient. The symptoms which had high scores were general syndromes while the symptoms which had low scores were specific manifestations of a certain patient. Common Chinese herbs corresponding to each syndrome factor were picked out, indirectly reflecting their frequencies in clinical application. CONCLUSION: Based on data mining of the relationship among the four diagnostic methods of TCM, syndrome factors and herbs, this study provided references for differentiation of TCM syndrome and selection of Chinese medicine according to clinical syndrome factors.

Development of new rabbit monoclonal antibody to progesterone receptor (Clone SP2): no heat pretreatment but effective for paraffin section immunohistochemistry.

Evaluation of estrogen and progesterone receptor (ER, PgR) status in breast cancer is widely used for the prediction of the response to endocrine therapy and as a biologic parameter closely related to disease prognosis. The IHC method is considered to be a specific, sensitive, and economical method for determining ER and PgR status. The authors developed the first rabbit anti-PgR mAb (clone SP2) used in IHC on formalin-fixed, paraffin-embedded tissue sections from breast carcinomas. This new antibody, compared with currently available anti-PgR antibodies, has important advantages, including its reactivity even without heat-based antigen retrieval of fixed-embedded tissue sections in IHC and the predominance of nuclear immunostaining with only very low cytoplasmic signal. A comparative study of IHC on 107 histologic specimens from breast cancer cases showed that SP2 yields the same results as the wellknown mouse mAb to PgR (clone 1A6). The antibody affinity of SP2 is 12 times higher than that of 1A6. Thus, SP2 may prove of great value in the assessment of PgR status in human breast cancer.