OBJECTIVES: To investigate the role of the calcium/calmodulin (CaM)-mediated activation of calcineurin (CN)-nuclear factor of activated T cells (NFAT) signaling pathway in mediating the regulatory effect of hyperforin (HY) on stress-induced depression-like disorder (DP) in mice. METHODS: C57BL/6J mice were randomly divided into control group, DP model group, and hyperforin treatment group (n=15). Behavioral changes of the mice were assessed using open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), light/dark box test (LDB), and novel object suppression test (NSFT). Immunohistochemistry was used to detect tyrosine hydroxylase (TH) expression in the CA1 region of the hippocampus, and serum serotonin (5-HT) and norepinephrine (NA) levels were detected with ELISA. Western blotting was used to analyze the expressions of TNF-α, IL-1β, IL-2, and CN-NFAT pathway proteins. In cultured BV-2 microglial cells with lipopolysaccharide (LPS) stimulation, the effects of hyperforin and CN inhibitor (CNIS) on expressions of ionized calcium-binding adapter molecule 1 (IBA-1), 5-HT, NA, inflammatory cytokines and CN-NFAT pathway proteins were examined using immunofluorescence assay, ELISA or Western blotting. RESULTS: Compared with the control mice, the mice in DP group showed significantly reduced activity in OFT, decreased sucrose consumption in SPT, reduced shuttle crossing in LDB, and lowered food intake in NSFT with significantly increased immobility in TST. The mice with DP showed significantly decreased TH-positive neurons, lowered 5-HT and NA levels, and increased expressions of TNF-α, IL-1β, IL-2 and CaM-CN-NFAT pathway proteins. In cultured BV-2 cells, LPS stimulation strongly increased cellular IBA-1 expression, decreased the levels of neurotransmitters (5-HT and NA), and increased the levels of inflammatory cytokines and CN-NFAT signaling, and these changes were effectively reversed by treatment with hyperforin or CNIS. CONCLUSIONS Hyperforin improves stress-induced depression-like behaviors in mice and activated BV-2 cells by targeting the CN-NFAT signaling pathway.
Animals ; Mice, Inbred C57BL ; Mice ; Microglia/drug effects* ; Depression/etiology* ; Perylene/pharmacology* ; Calcineurin/metabolism* ; NFATC Transcription Factors/metabolism* ; Calcium Signaling/drug effects* ; Stress, Psychological ; Phloroglucinol/pharmacology* ; Signal Transduction ; Male ; Behavior, Animal/drug effects* ; Terpenes

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder that is more common in women of childbearing age, which seriously affects women's quality of life and fertility, taking a toll on both physical and mental health as well as economic capacity. At present, the problems of thin ovulation and endocrine disorders in PCOS patients can be corrected by fertility drugs, but the endometrial receptivity of the patients is still in a poor state, and there is still a situation of inability to conceive. Current studies have shown that endometrial receptivity defects in PCOS patients are closely related to abnormal expression of metabolism, immunity, hormones and their receptors, etc. However, the specific pathological mechanism and etiology have not been fully clarified. This paper mainly discusses the factors of endometrial receptivity defects in patients with PCOS, and focuses on three aspects: genetic and epigenetic abnormalities, metabolic abnormalities, and immune disorders, trying to provide some clues for future treatment options and new drug targets for PCOS patients.

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder that is more common in women of childbearing age, which seriously affects women's quality of life and fertility, taking a toll on both physical and mental health as well as economic capacity. At present, the problems of thin ovulation and endocrine disorders in PCOS patients can be corrected by fertility drugs, but the endometrial receptivity of the patients is still in a poor state, and there is still a situation of inability to conceive. Current studies have shown that endometrial receptivity defects in PCOS patients are closely related to abnormal expression of metabolism, immunity, hormones and their receptors, etc. However, the specific pathological mechanism and etiology have not been fully clarified. This paper mainly discusses the factors of endometrial receptivity defects in patients with PCOS, and focuses on three aspects: genetic and epigenetic abnormalities, metabolic abnormalities, and immune disorders, trying to provide some clues for future treatment options and new drug targets for PCOS patients.

Objective:To find out a specific group of patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) who can benefit from endometrial microstimulation (EM) and how to maximize the effect. Methods:A retrospective case-control study on 1916 cycles from women who underwent EM in Center for Reproductive Medicine, Shandong University between 2006 to 2018. Their baseline characteristics and cycle parameters were analyzed as well as the differences in EM procedures. Results:There were 1435 cycles from women ≤35 years old (867 succeeded in implantation and 568 failed) and 481 cycles from women >35 years old (179 succeeded in implantation and 302 failed). Among women ≤35 years old, compared with those who failed to implant, those who succeeded had thicker endometrium [(1.07±0.20) cm vs. (1.02±0.20) cm, OR=5.01, P<0.001] and a larger proportion of A/A- endometrial type (91.3% vs. 85.3%, OR=1.88, P=0.01) observed on trigger day. As for patients >35 years old, women who succeeded in implantation had thicker endometrium than those who failed in implantation [(1.05±0.19) cm vs. (0.96±0.22) cm, OR=8.73, P<0.001]. In addition, EM in luteal phase resulted in a significantly higher implantation rate in the >35 years old group compared with that when EM in follicular phase (42.9% vs. 32.7%, P=0.02). Conclusion:As for patients who were suggested to do the EM therapy, those ≤ 35 years old with better endometrium condition (thicker and A/A- endometrial type) or women >35 years old with thicker endometrium may benefit from EM, and EM in luteal phase increases implantation rates among >35-year-old patients compared with that when EM in follicular phase.

Objective:To find out a specific group of patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) who can benefit from endometrial microstimulation (EM) and how to maximize the effect. Methods:A retrospective case-control study on 1916 cycles from women who underwent EM in Center for Reproductive Medicine, Shandong University between 2006 to 2018. Their baseline characteristics and cycle parameters were analyzed as well as the differences in EM procedures. Results:There were 1435 cycles from women ≤35 years old (867 succeeded in implantation and 568 failed) and 481 cycles from women >35 years old (179 succeeded in implantation and 302 failed). Among women ≤35 years old, compared with those who failed to implant, those who succeeded had thicker endometrium [(1.07±0.20) cm vs. (1.02±0.20) cm, OR=5.01, P<0.001] and a larger proportion of A/A- endometrial type (91.3% vs. 85.3%, OR=1.88, P=0.01) observed on trigger day. As for patients >35 years old, women who succeeded in implantation had thicker endometrium than those who failed in implantation [(1.05±0.19) cm vs. (0.96±0.22) cm, OR=8.73, P<0.001]. In addition, EM in luteal phase resulted in a significantly higher implantation rate in the >35 years old group compared with that when EM in follicular phase (42.9% vs. 32.7%, P=0.02). Conclusion:As for patients who were suggested to do the EM therapy, those ≤ 35 years old with better endometrium condition (thicker and A/A- endometrial type) or women >35 years old with thicker endometrium may benefit from EM, and EM in luteal phase increases implantation rates among >35-year-old patients compared with that when EM in follicular phase.