RESUMEN
BACKGROUND: Chronic stress has been known to impair the female reproductive function, but the mechanism remains to be further investigated. Chaiyu-Dixian Formula (CYDXF) has been reported to regulate human endocrine disorders clinically. However, whether this formula can affect chronic stress-induced ovarian follicular development is not clear. AIM OF THE STUDY: To examine effects of CYDXF on follicular development and explore possible mech anisms in a chronic unpredictable mild stress (CUMS) model. MATERIALS AND METHODS: Adult female rats were randomly divided into 5 groups control group, CUMS group (saline treatment), CUMS+Estradiol (E2) (0.1 mg/kg) group, CUMS+CYDXF (2.73 g/kg) group, and CUMS+CYDXF (5.46 g/kg) group. Body weights and behavioral tests were documented. Serum hormone levels were determined by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the protein levels in the PI3K/Akt pathway and brain-derived neurotrophic factor (BDNF). The follicles were analyzed and classified according to their morphological characterization. RESULTS: CYDXF relieved depression-like behaviors and ameliorated the abnormality in rat estrous cycle within the rat model of CUMS. Moreover, CYDXF could regulate endocrine disorders, increase the proportion of antral follicles as well as decrease the proportion of follicular atresia, which suggested that CYDXF could alleviate abnormal follicular development and improve overall ovarian function. Furthermore, CYDXF also activated the BDNF-mediated PI3K/Akt signaling pathway. CONCLUSIONS: CYDXF (at dose of both 2.73 and 5.46 g/kg) attenuated chronic stress-induced abnormal ovarian follicular development by relieving depression-like behaviors and improving ovarian function through partly the regulation of the BDNF-mediated PI3K/Akt pathway.
RESUMEN
The prognostic significance of tumor-associated macrophages (TAMs) in multiple myeloma (MM) in the era of novel drugs remains unclear. CD163 expression was detected by immunohistochemistry to determine the number of TAMs in 198 MM patients receiving bortezomib-based regimens and the data were used to evaluate its relevance with clinical characteristics, treatment response, and prognosis. Patients with high levels of infiltrated CD163+ TAMs (>55/HPF) at diagnosis tended to have more adverse clinical characteristics. Patients with high CD163+ TAM content (>55/HPF) at diagnosis had worse progression-free survival (PFS) (P<0.001) and overall survival (OS) (P<0.001),and achieved lower complete remission (CR)/near-CR rate (P<0.001), than patients with low CD163+ TAM levels. Multivariate analysis revealed that CD163+ TAM content was an independent adverse prognostic factor for PFS and OS. Our data indicated that CD163+ TAM content at diagnosis is a powerful predictor of prognosis for MM in the era of novel drugs, and this discovery offers new insight into potential therapeutic strategies.
