Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.

Oleanolic acid (OA) and ursolic acid (UA) are isomeric triterpenic acids and only one methyl's position is different between them. OA and UA always exist in the same plant, so it is difficult to separate them when determining contents by RP-HPLC. In this study, a very simple mobile phase for HPLC was developed to simultaneously determine UA and OA, and the factors affecting separation were also discussed. The mobile phase is methanol: water (95:5) with flow rate 0.4 mL/min. The retention time for OA and UA was 20.58 and 21.57 min, respectively, the resolution was 1.61. The average contents of OA and UA of three Loquat leaves sets were 1.4 mg/g and 5.6 mg/g, respectively. Regarding the HPLC, we found that changing mobile phase, adjusting the pH value or adding ion-pairing agent could not affect the separation between UA and OA greatly. While adjustment of the flow rate and column temperature could improve the resolution greatly.

Epidemiological studies on the association between SULT1A1 codon 213 polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was conducted in this article. Sixteen studies including 9,881 cases and 13,564 controls were collected for SULT1A1 codon 213 polymorphism by searching the databases of Medline, PubMed, Embase, and ISI Web of Knowledge. The strength of association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 21 studies were pooled into the meta-analysis, there was no evidence for significant association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility (for Arg/Arg versus Arg/His: OR = 0.999, 95% CI = 0.941-1.061; for Arg/Arg versus His/His: OR = 1.121, 95% CI = 1.013-1.242; for dominant model: OR = 1.128, 95% CI = 1.01-1.26; for recessive model: OR = 1.151, 95% CI = 0.950-1.394). In the subgroup analysis by the source of controls, significant increased risk was found for hospital-based studies (for Arg/Arg versus Arg/His: OR = 1.173, 95% CI = 1.000-1.376; for Arg/Arg versus His/His: OR = 1.600, 95% CI = 1.134-2.256; for dominant model: OR = 1.269, 95% CI = 1.134-2.256; for recessive model: OR = 1.664, 95% CI = 1.070-2.588). In summary, the meta-analysis suggests that SULT1A1 codon 213 polymorphism may be associated with the hospital-based studies. However, large number of samples and representative hospital-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

Chronic pharyngitis, a chronic inflammation of the pharyngeal mucous membrane and submucous lymphoid tissues, is often caused by unsatisfactory treatment of acute pharyngitis or repeated occurrences of upper respiratory tract infection and is related to a high-dust environment. Traditional herbal pharmacotherapy is well known for combining plant species to create complex phytochemical mixtures in the attempt to ameliorate pathophysiological processes. The aim of current study is to investigate the effect of immunoregulation and anti-inflammation with the traditional Chinese medicine (TCM) "Li-Yan Zhi-Ke Granule" in rats. Determination of serum hemolysin and the carbon particle clearance test were performed. The results demonstrate that administration of the TCM "Li-Yan Zhi-Ke Granule" may improve the effect of phagocytosis by mononuclear macrophages and immune function in rats, and may also increase the immunoregulatory and anti-inflammatory responses of rats with chronic pharyngitis. This traditional drug could relieve the symptoms of sore throat and cough in rats with chronic pharyngitis.

The E3 ubiquitin protein ligase Casitas B-lineage Lymphoma (Cbl) proteins and their binding partners play an important role in regulating signal transduction pathways. It is important to utilize regulators to study the protein-protein interactions (PPIs) between these proteins. However, finding specific small-molecule regulators of PPIs remains a significant challenge due to the fact that the interfaces involved in PPIs are not well suited for effective small molecule binding. We report the development of a competitive, homogeneous, high-throughput fluorescence polarization (FP) assay to identify small molecule regulators of Cbl (RING) domain. The FP assay was used to measure binding affinities and inhibition constants of UbCH7 peptides and small molecule regulators of Cbl (RING) domains, respectively. In order to rule out promiscuous, aggregation-based inhibition, two assay conditions were developed and compared side by side. Under optimized conditions, we screened a 10,000 natural compound library in detergent-free and detergent-present (0.01% Triton X-100) systems. The results indicate that the detergent-present system is more suitable for high-throughput screens. Three potential compounds, methylprotodioscin, leonuride and catalpol, have been identified that bind to Cbl (RING) domain and interfere with the Cbl (RING)-UbCH7 protein-protein interaction.