Emerging evidence has demonstrated that melatonin (MT) plays a crucial role in regulating mammalian reproductive functions. It has been reported that MT has a protective effect on polycystic ovary syndrome (PCOS). However, the protective mechanisms of MT remain poorly understood. This study aims to explore the effect of MT on ovarian function in PCOS and to elucidate the relevant molecular mechanisms in vivo and in vitro. We first analysed MT expression levels in the follicular fluid of PCOS patients. A significant reduction in MT expression levels was noted in PCOS patients. Intriguingly, reduced MT levels correlated with serum testosterone and inflammatory cytokine levels in follicular fluid. Moreover, we confirmed the protective function of MT through regulating autophagy in a DHEA-induced PCOS rat model. Autophagy was activated in the ovarian tissue of the PCOS rat model, whereas additional MT inhibited autophagy by increasing PI3K−-Akt pathway expression. In addition, serum-free testosterone, inflammatory and apoptosis indexes were reduced after MT supplementation. Furthermore, we also found that MT suppressed autophagy and apoptosis by activating the PI3K-Akt pathway in the DHEA-exposed human granulosa cell line KGN. Our study showed that MT ameliorated ovarian dysfunction by regulating autophagy in DHEA-induced PCOS via the PI3K-Akt pathway, revealing a potential therapeutic drug target for PCOS.

The development and application of high-throughput omics technologies have enabled a more in-depth understanding of mitochondrial biosynthesis metabolism and the pathogenesis of mitochondrial diseases. In accordance with this, a host of new treatments for mitochondrial disease are emerging. As an essential pathway in maintaining mitochondrial proteostasis, the mitochondrial unfolded protein response (UPR^mt) is not only of considerable significance for mitochondrial substance metabolism but also plays a fundamental role in the development of mitochondrial diseases. Furthermore, in mammals, the integrated stress response (ISR) and UPR^mt are strongly coupled, functioning together to maintain mitochondrial function. Therefore, ISR and UPR^mt show great application prospects in the treatment of mitochondrial diseases. In this review, we provide an overview of the molecular mechanisms of ISR and UPR^mt and focus on them as potential targets for mitochondrial disease therapy.

Background: Immunocytochemistry and RT-PCR have been widely used for the detection of circulating tumor cells in patients with breast cancer but their specificity is limited. Our purpose is to utilize a convenient and specific technology to detect circulating tumor cells in breast cancer patients. Methods: To determine the sensitivity and specificity of our method, A431 cells were serially diluted with human peripheral blood leukocytes and stained with CK19. A total of 73 blood specimens including 25 healthy volunteers and 48 patients with breast carcinoma and benign tumor were tested by flow cytometry to quantify the expression of CK19. Results: The detectable upper limit of A431 cells was 1 cancer cell among 10⁴ human white blood cells. CK19 was detected in 27% of breast cancer patients but none control gives positive result. The number of cancer cells increased gradually along with the disease stages for it was the least in stage I (0%) and the most in stage IV (1.29%). Fifteen patients were observed during three month chemotherapy after surgery, and most of their CK19 expression levels declined after treatment. Conclusion: Our research convinces that the detection of CK19 in peripheral blood by flow cytometry is also a specific and feasible method to monitor circulating tumor cells in breast cancer.