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

Objective To evaluate the diagnostic value of one-stop cardiac CT (stress dynamic CT-MPI combining with CTA) in CAD. Methods Thirty patients underwent CCTA combined with stress dynamic CT-MPI and stress SPECT-MPI including 16 patients underwent ICA were retrospectively enrolled. All procedures were performed within 2 weeks without related treatment. CT-MPI and SPECT-MPI were evaluated visually and MBF was quantified according to dynamic CT-MPI which was compared through paired t test. The diagnostic value of CT-MPI for myocardial ischemia was evaluated with SPECT-MPI as the reference standard. The consistency between the two techniques was determined by Kappa test. With SPECT combined with ICA as the reference standard, we evaluated the value of CT-MPI and its combination with CCTA in the diagnosis of CAD with hemodynamic stenosis. Results On stress CT-MPI, 19 of 30 patients and 52 segments were evaluated with myocardial perfusion defects. There was a significant difference in MBF values between normal[(117.61±29.82)ml·100 ml-1·min-1] and hypoperfused [(80.60±22.15)ml·100 ml - 1 · min - 1] segments (t=15.764,P<0.001). With SPECT as reference standard, the sensitivity, specificity were 94.12% (32/34), 95.80% (456/476) on the vessel basis. The Kappa value of the two examinations was 0.772(P<0.001). As for the 16 patients who also underwent ICA, 15 patients with 22 vessel-areas had hemodynamic stenosis on CT-MPI. Compared with SPECT combined with ICA, the sensitivity, specificity for detecting hemodynamic stenosis were 92.31% (12/13), 71.43% (25/35) for CT-MPI;100%(13/13), 51.43%(18/35) for CTA and 92.31%(12/13), 82.86%(29/35) for CT-MPI combined with CTA, respectively. Moderate correlation was observed between the combination of CT-MPI and CCTA and reference standard (r=0.690,P<0.001). Conclusion Stress dynamic CT-MPI can detect myocardial perfusion defects and hemodynamic changes and improves the diagnostic ability of functional stenosis of CAD combined with CTA, which can finally achieve the one-stop mode of cardiac CT in CAD.

Objective To evaluate the efficacy and safety of REXEEDTM series highflux dialyzer. Methods A randomized cross-over study of 3×3 Latin square was designed based on the surface area of dialyzer membrane (1.5 m2 and 2.1 m2). Seventy-two stable maintenance hemodialysis (MHD) patients from Shanghai Renji Hospital and Ruijin Hospital were enrolled in this study for 3 consecutive weeks. REXEEDTM-15AC, 15UC, 21AC, 21UC dialyzers were used as trial group and APS-15U,BIO-HX100 dialyzers were used as control group. The clearances of urea, creatinine, phosphorus and β2-microglobulin were calculated. Adverse event and adverse reactions were recorded. Results There were significantly higher urea and creatinine clearance in 1SAC and 15UC dialyzers as compared to APS-15U dialyzer [(222.07±18.74) mi/min, (220.23±26.26) ml/min vs (199.56±14.21) ml/min; (176.73±16.41) ml/min, (175.22±25.94) ml/min vs (165.42±14.68) ml/min, all P<0.05]. There were significantly higher urea, creatinine and β2-microglobulin clearance in 21AC and 21UC dialyzer as compared to BIO-HX100 dialyzer [(230.59±15.24) ml/min, (233.96±7.06) ml/min vs (203.43±36.66) ml/min; (183.50±25.90) ml/min, (181.05±23.94) ml/min vs (166.25±29.82) ml/min; (111.77±53.42) ml/min, (125.54±51.99) ml/min vs (42.39±4.81) ml/min; all P<0.05]. There was no significant difference of phosphorus clearance between REXEEDTM series dialyzers and control dialyzers. The efficiency of urea clearance and urea reduction ratio could achieve clinical targets in REXEEDTM series. Conclusion REXEEDTM series highflux dialyzers are effective and safe for clinical application.