No abstract

Tyrosine kinase inhibitors (TKIs) provide more effective targeted treatments for cancer, but are subject to a variety of adverse effects, such as hypothyroidism. TKI-induced hypothyroidism is a highly complicated issue, because of not only the unrealized toxicological mechanisms, but also different incidences of individual TKI drugs. While sunitinib is suspected for causing thyroid dysfunction more often than other TKIs, sorafenib is believed to be less risky. Here we integrated clinical data and in silico drug-protein interactions to examine the pharmacological distinction between sunitinib and sorafenib. Statistical analysis on the FDA Adverse Event Reporting System (FAERS) confirmed that sunitinib is more concurrent with hypothyroidism than sorafenib, which was observed in both female and male patients. Then, we used docking method and identified 3 proteins specifically binding to sunitinib but not sorafenib, i.e., retinoid X receptor alpha, retinoic acid receptors beta and gamma. As potential off-targets of sunitinib, these proteins are well known to assemble with thyroid hormone receptors, which can explain the profound impact of sunitinib on thyroid function. Taken together, we established a strategy of integrated analysis on clinical records and drug off-targets, which can be applied to explore the molecular basis of various adverse drug reactions.

PurposeThe purpose of this paper is to explore the structure, implicit attitude and consequences of followers' implicit followership theories in the Chinese cultural context through three studies. Study 1 explores the structure of followers' implicit followership theories. Study 2 examines the implicit attitude of followers towards followers' implicit followership theories. Study 3 verifies the impact of followers' implicit followership theories on the quality of collegial relationships.Design/methodology/approachThe data for study 1 (n = 321) and study 3 (n = 243) were collected through an online self-report questionnaire, and the data for study 2 (n = 30) were collected through the go/no-go association task.FindingsThe structure of followers' implicit followership theories includes two dimensions: positive followership prototypes and negative followership prototypes. Followers' implicit attitudes were more likely to match positive followership prototypes than negative followership prototypes. Positive followership prototypes had a significantly positive impact on the quality of collegial relationships, whereas negative followership prototypes had a significantly negative impact on the quality of collegial relationships.Research limitations/implicationsThe psychology and behaviour of employees can be better understood by exploring followers' implicit followership theories.Practical implicationsEmployees hold a relatively positive implicit attitude towards followers. Therefore, managers should provide positive feedback to improve employees' positive self-cognition so that employees can better serve the organization and better promote its development.Originality/valueThe paper is one of the few studies to explore followers' implicit followership theories in the Chinese cultural context.

No abstract

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) is one of the key targets of insulin resistance research, in addition to being ligand-activated transcription factors of the nuclear hormone receptor superfamily with a leading role in adiposeness activation and insulin sensitivity. They regulate cholesterol and carbohydrate metabolism through direct actions on gene expression. Despite their therapeutic importance, there are dose limiting side effects associated with PPARγ drug treatments, thus a new generation of safer PPARγ drugs are being actively sought after treatment. Methods: In this study, we used computer aided drug design to screen new series of PPARγ ligands, and synthesized a series of potential thiazolidinedione derivatives such as 5,7- dibenzyloxybenzyl-3-hydroxymethyl-4H-coumarin-4-ketone, using 4-steps to synthesize the target compounds and built streptozotocin (STZ) induced insulin resistance rat model to measure their antidiabetic activity. Results: We found that 10 mg/kg concentration of compound 0701C could significantly decrease blood glucose and serum PPARγ, serum insulin levels in insulin resistance model rat. Conclusion: We would conclude that compound 0701C might serve as a potential PPARγ partial agonist.