Biological Relevance of the Interaction Between Resveratrol and Insulin

In view of synergistic effect of resveratrol and insulin in the prevention and treatment of many chronic diseases, the interaction between them was studied and its biological implication was further discussed. Insulin could interact with resveratrol to form 1:1 complex with the binding constant of 1.03?×?10³ M^?1 at 298 K. The binding was spontaneous and insulin/resveratrol complex formation was an exothermal reaction. Hydrogen bond and van der Waals force played key roles in the binding process. Kinetic study indicates that resveratrol binding to insulin conformed to the first-order exponential decay function. The interaction decreased the polarity around tyrosine residue and α-helical content, destroyed the disulfide bridges, depolymerized insulin dimers to monomer, and altered the orientation of aromatic side chains in the insulin. Additionally, insulin increased resveratrol stability. These results well confirm synergistic effect of resveratrol and insulin in vitro. It would give a deeper insight into resveratrol as a kind of food functional factor.     

Prediction of Drug-Target Interactions for Drug Repositioning Only Based on Genomic Expression Similarity

Small drug molecules usually bind to multiple protein targets or even unintended off-targets. Such drug promiscuity has often led to unwanted or unexplained drug reactions, resulting in side effects or drug repositioning opportunities. So it is always an important issue in pharmacology to identify potential drug-target interactions (DTI). However, DTI discovery by experiment remains a challenging task, due to high expense of time and resources. Many computational methods are therefore developed to predict DTI with high throughput biological and clinical data. Here, we initiatively demonstrate that the on-target and off-target effects could be characterized by drug-induced in vitro genomic expression changes, e.g. the data in Connectivity Map (CMap). Thus, unknown ligands of a certain target can be found from the compounds showing high gene-expression similarity to the known ligands. Then to clarify the detailed practice of CMap based DTI prediction, we objectively evaluate how well each target is characterized by CMap. The results suggest that (1) some targets are better characterized than others, so the prediction models specific to these well characterized targets would be more accurate and reliable; (2) in some cases, a family of ligands for the same target tend to interact with common off-targets, which may help increase the efficiency of DTI discovery and explain the mechanisms of complicated drug actions. In the present study, CMap expression similarity is proposed as a novel indicator of drug-target interactions. The detailed strategies of improving data quality by decreasing the batch effect and building prediction models are also effectively established. We believe the success in CMap can be further translated into other public and commercial data of genomic expression, thus increasing research productivity towards valid drug repositioning and minimal side effects.     

A novel Aurora-A-mediated phosphorylation of p53 inhibits its interaction with MDM2

Purpose: Crosstalk between Aurora-A kinase and p53 has been proposed. While the genetic amplification of Aurora-A has been observed in many human cancers, how p53 is regulated by Aurora-A remains ambiguous. In this study, Aurora-A-mediated phosphorylation of p53 was analyzed by mass spectrometry in order to identify a new phosphorylation site. Subsequently, the functional consequences of such phosphorylation were examined. Experimental design: In vitro phosphorylation of p53 by Aurora-A was performed and the phosphorylated protein was then digested with trypsin and enriched for phosphopeptides by immobilized metal affinity chromatography. Subsequently, a combination of β-elimination and Michael addition was applied to the phosphopeptides in order to facilitate the identification of phosphorylation sites by MS. The functional consequences of the novel phosphorylation of p53 on the protein–protein interactions, protein stability and transactivation activity were then examined using co-immunoprecipitation, Western blotting and reporter assays. Results: Ser-106 of p53 was identified as a novel site phosphorylated by Aurora-A. A serine-to-alanine mutation at this site was found to attenuate Aurora-A-mediated phosphorylation in vitro. In addition, phosphate-sensitive Phos-tag SDS-PAGE was used to confirm that the Ser-106 of p53 is in vivo phosphorylated by Aurora-A. Finally, co-immunoprecipitation studies suggested that Ser-106 phosphorylation of p53 decreases its interaction with MDM2 and prolongs the half-life of p53. Conclusions: The inhibition of the interaction between p53 and MDM2 by a novel Aurora-A-mediated p53 phosphorylation was identified in this study and this provides important information for further investigations into the interaction between p53 and Aurora-A in terms of cancer biology.     

复方玄驹胶囊治疗精液液化异常的临床研究

目的：观察复方玄驹胶囊治疗精液液化异常的临床疗效。方法：选择2010年1月至2012年1月在广西医科大学第四附属医院男性科门诊精液液化异常患者182例,采用简单随机分组,其中100例口服复方玄驹胶囊,82例口服生精胶囊为对照组,观察患者治疗前后精子质量及精液液化状态。结果：两组患者在治疗少、弱精方面均较同组治疗前差异有统计学意义（P〈0.05）,在治疗精液液化异常方面,复方玄驹胶囊治疗组总有效率及治愈率较生精胶囊对照组差异均有统计学意义（P〈0.05）。结论：复方玄驹胶囊对少、弱精子症并精液液化异常具有较好的疗效,可作为治疗男性不育症的一种有效治疗方法。     

Tangshenosides from Codonopsis lanceolata roots

A new symmetrical phenylpropanoid glycoside, tangshenoside VIII (1), together with six known tangshenosides (2–7) were isolated from the roots of Codonopsis lanceolata (Campanulaceae). Their structures were established on the basis of spectroscopic data, including two-dimensional NMR analyses. Tangshenosides have chemotaxonomic significance.     

Cancer survival in patients with HIV/AIDS in the era of highly active antiretroviral therapy in Taiwan: A population-based cohort study

Objectives: HIV-related immunosuppression has been associated with the development of AIDS-defining malignancies. We examined the overall survival of HIV-infected patients who developed cancer. Design: A retrospective cohort study. Methods: Using the Taiwan Longitudinal Health Insurance Database, we compared patients diagnosed with HIV (n = 9918) between January 1, 2002, and December 31, 2007 with age-matched controls (n = 99,180). Each patient was followed until the end of 2009 (least 2 years after the initial HIV diagnosis) to evaluate the incidence of malignancies. Results: The risk of overall malignancies in the HIV-infected cohort was 1.88 times higher than the risk of a first malignancy in the age-matched non-HIV infected cohort (incidence rate ratio [IRR]) = 2.05, p < 0.0001). The diagnosis of a malignancy was negatively correlated with survival in the HIV-infected cohort (p < 0.0011), and HIV infection had a synergistic effect on the survival of patients with malignancies compared with the non-HIV infected cohort, all of who had been newly diagnosed with cancer (p < 0.0001). However, the difference in the risk of developing nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Taiwan, between the two cohorts was not significant (IRR = 0.22, 95% CI = 0.03–1.65). Conclusions: The risk of cancer in HIV-infected patients in Taiwan has increased significantly in the era of highly active antiretroviral therapy. A history of HIV significantly affected the survival of the patients in our study cohort after they developed cancer.Evidence level: 2B.