Cyproterone Acetate/Ethinylestradiol

Alzheimer's disease (AD), the most common contributor to dementia, is a growing global health problem. This study aimed to investigate the role of lemur tyrosine kinase 2 (LMTK2) in AD as well as its relevant mechanism. To establish an in vitro cell model, PC12 cells were challenged with 20 µmol/l Ab 25-35 for 24 h. RT-qPCR and western blot examined LMTK2 mRNA and protein expressions. With the application of CCK-8, TUNEL, iron colorimetric assay kit and DCFH-DA, the viability, apoptosis, Fe 2+ and ROS content in PC12 cells were assessed. Besides, the expressions of oxidative stress-, apoptosis-, ferroptosis- and Nrf2/ARE signalling-related proteins were evaluated with western blot. Moreover, commercial kits examined SOD, MDA and CAT contents. The results manifested that LMTK2 expression was noticeably downregulated in Ab 25-35 -treated PC12 cells. Notably, LMTK2 overexpression exhibited inhibitory effects on oxidative stress, apoptosis and ferroptosis in PC12 cells exposed to Ab 25-35 . The upregulated Nrf2, NQO1 and HO-1 expressions in LMTK2 overexpressed-PC12 cells with Ab 25-35 induction revealed that LMTK2 overexpression could activate the Nrf2/ARE signalling pathway. What is more, a series of cellular experiments further testified that ML385, a specific Nrf2 inhibitor, partly hindered the protective role of LMTK2 overexpression against Ab 25-35 -triggered oxidative stress, apoptosis and ferroptosis in PC12 cells. In conclusion, LMTK2 overexpression alleviated the ferroptosis, oxidant damage and apoptosis in PC12 cells exposed to Ab 25-35 through the activation of the Nrf2/ARE signalling pathway, indicating the potential target of LMTK2 in the treatment of AD.

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disorder that is closely associated with the proliferation and apoptosis of ovarian granulosa cells (GCs). Ampelopsis japonica (AJ) is the dried tuberous root of Ampelopsis japonica (Thunb.) Makino (A. japonica), with anti-inflammatory, antioxidant, antibacterial, antiviral, wound-healing, and antitumor properties; however, it is unclear whether this herb has a therapeutic effect on PCOS. Therefore, this study aimed to investigate the pharmacological effect of AJ on PCOS and reveal its potential mechanism of action. A PCOS rat model was established using letrozole. After establishing the PCOS model, the rats received oral treatment of AJ and Diane-35 (Positive drug: ethinylestradiol + cyproterone tablets) for 2 weeks. Lipidomics was conducted using liquid-phase mass spectrometry and chromatography. AJ significantly regulated serum hormone levels and attenuated pathological variants in the ovaries of rats with PCOS. Furthermore, AJ significantly reduced the apoptotic rate of ovarian GCs. Lipidomic analysis revealed that AJ modulated glycerolipid and glycerophospholipid metabolic pathways mediated by lipoprotein lipase (Lpl), diacylglycerol choline phosphotransferase (Chpt1), and choline/ethanolamine phosphotransferase (Cept1). Therefore, we established that AJ may reduce ovarian GC apoptosis by modulating lipid metabolism, ultimately improving ovulatory dysfunction in PCOS. Therefore, AJ is a novel candidate for PCOS treatment.