Tip60-FOXO regulates JNK signaling mediated apoptosis in Drosophila.

The JNK signaling pathway plays crucial roles in various physiological processes, including cell proliferation, differentiation, migration, apoptosis, and stress response. Dysregulation of this pathway is closely linked to the onset and progression of numerous major diseases, such as developmental defects and tumors. Identifying and characterizing novel components of the JNK signaling pathway to enhance and refine its network hold significant scientific and clinical importance for the prevention and treatment of associated cancers. This study utilized the model organism Drosophila and employed multidisciplinary approaches encompassing genetics, developmental biology, biochemistry, and molecular biology to investigate the interplay between Tip60 and the JNK signaling pathway, and elucidated its regulatory mechanisms. Our findings suggest that loss of Tip60 acetyltransferase activity results in JNK signaling pathway activation and subsequent induction of JNK-dependent apoptosis. Genetic epistasis analysis reveals that Tip60 acts downstream of JNK, paralleling with the transcription factor FOXO. The biochemical results confirm that Tip60 can bind to FOXO and acetylate it. Introduction of human Tip60 into Drosophila effectively mitigates apoptosis induced by JNK signaling activation, underscoring conserved regulatory role of Tip60 in the JNK signaling pathway from Drosophila to humans. This study further enhances our understanding of the regulatory network of the JNK signaling pathway. By revealing the role and mechanism of Tip60 in JNK-dependent apoptosis, it unveils new insights and potential therapeutic avenues for preventing and treating associated cancers.

Associations of oxytocin with metabolic parameters in obese women of childbearing age.

INTRODUCTION: The aim of this study was to compare plasma oxytocin levels in obese women of childbearing age with non-obese women of childbearing age, and to investigate the relationship between plasma oxytocin levels and metabolic parameters (including blood glucose, insulin resistance, blood lipid, and blood pressure). MATERIAL AND METHODS: A total of 151 obese women of childbearing age and 160 non-obese women of childbearing age were enrolled in this study. Plasma oxytocin levels were measured by electrochemiluminescence immunoassays. Height, body weight, body mass index (BMI), fasting blood glucose (FBG), fasting insulin (FI), homeostasis model assessment for insulin resistance (HOMA-IR), total triglycerides (TG), total cholesterol (TC), low-density lipoprotein-C (LDL-C), high-density lipoprotein-C (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured in all subjects. Quantile regression analysis was used to analyse the associations of plasma oxytocin levels with FBG, FI, HOMA-IR, TG, TC, LDL-C, HDL-C, SBP, and DBP. RESULTS: In obese women of childbearing age, plasma oxytocin levels were lower compared with non-obese controls. After adjusting for age, quantile regression analysis showed that the plasma oxytocin levels were inversely associated with HOMA-IR at the quantile level between 0.27 and 0.79 (i.e. the HOMA-IR level of 2.11 and 3.07, respectively), the plasma oxytocin levels were inversely associated with TC after the quantile level of 0.21 (i.e. the TC level of 3.78 ), and the plasma oxytocin levels were inversely associated with LDL-C at all quantile levels of LDL-C. In addition, the plasma oxytocin levels showed a positive association with HDL-C at all quantile levels of HDL-C. No significant associations were found between the plasma oxytocin levels and FBG, FI, TG, SBP, and DBP. CONCLUSIONS: Oxytocin deficiency was common in obese women of childbearing age. Oxytocin showed negative correlation with HOMA-IR, TC, and LDL-C, while it showed positive association with HDL-C. Our findings suggest that oxytocin played an important role in inhibiting metabolic disorders associated with obesity in women of childbearing age.