Soluble 3',6-substituted indirubins with enhanced selectivity toward glycogen synthase kinase -3 alter circadian period

Glycogen synthase kinase -3 (GSK-3) is a key enzyme involved in numerous physiological events and in major diseases, such as Alzheimer's disease, diabetes, and cardiac hypertrophy. Indirubins are bis-indoles that can be generated from various natural sources or chemically synthesized. While rather potent and selective as GSK-3 inhibitors, most indirubins exhibit low water solubility. To address the issue of solubility, we have designed novel analogues of 6-bromo-indirubin-3'-oxime with increased hydrophilicity based on the GSK-3/indirubins cocrystal structures. The new derivatives with an extended amino side chain attached at position 3' showed potent GSK-3 inhibitory activity, enhanced selectivity, and dramatically increased water solubility. Furthermore, some of them displayed little or no cytotoxicity. The new indirubins inhibit GSK-3 in a cellular reporter model. They alter the circadian period measured in rhythmically expressing cell cultures, suggesting that they might constitute tools to investigate circadian rhythm regulation.     

人工牛黄与几种新配方的药理学比较研究（Ⅱ）

用比较药理学研究方法，对人工牛黄新配方Ｅ、Ｆ和Ｇ与现在药用人工牛黄的主要药效学在同等条件下进行了比较。结果表明，与现在药用人工牛黄一样，人工牛黄新配方Ｅ、Ｆ和Ｇ具有镇静、抗惊厥、解热、抗炎、增强非特异性免疫、护肝作用，作用强度与现在药用人工牛黄相近，或更强。     

Proposal for a Combined Histomolecular Algorithm to Distinguish Multiple Primary Adenocarcinomas from Intrapulmonary Metastasis in Patients with Multiple Lung Tumors

Introduction

Multiple nodules in the lung are being diagnosed with an increasing frequency thanks to high-quality computed tomography imaging. In patients with lung cancer, this situation represents up to 10% of patients who have an operation. For clinical management, it is important to classify the disease as intrapulmonary metastasis or multiple primary lung carcinoma to define TNM classification and optimize therapeutic options. In the present study, we evaluated the respective and combined input of histological and molecular classification to propose a classification algorithm for multiple nodules.