Fig 2: In vivo antidepressive effects of nanocapsules. A In vivo Cy7.5 fluorescence of C57BL/6J mice and CUMS mice after intravenous injection with VCNCs-Cy7.5, CNCs-Cy7.5, and VNCs-Cy7.5 at 400 μg 5-HT/kg for 3 h and 7 h. Living Cy 5.5 fluorescence images of mice after treatment with VCNCs-Cy5.5, CNCs-Cy5.5, and VNCs -Cy5.5 (C5-HT: 400 μg /kg) for 3 h. The representative western blot analysis of B Nrf 2 in the hippocampus of brain across all groups. The other two replicates were presented in Additional file 1: Fig. S38. Reverse transcription quantitative polymerase chain reaction analysis (RT-qPCR) of relative mRNA levels of C NLRP3 in the hippocampi of mice in all groups (n = 3). The levels of hippocampal D IL-6 in the mice hippocampi after treatment were detected using ELISA kits. The results were normalized by the protein concentration of each sample (n = 3). E ROS/DAPI staining and F GFAP / DAPI staining brains in groups subjected to different treatments. Analysis of hippocampal BDNF expression using G western blot, H RT-qPCR, I ELISA kits and J immunohistochemistry slides. The significant differences between groups were analyzed using the one-way ANOVA method, *P < 0.05, **P < 0.01, *** P < 0.001

Fig 3: GA reverse SD-induced synaptic impairment and the change of oxidative stress factor. (A) Sample traces showing sEPSCs. (B) There are no changes of average sEPSC amplitude both in each group. Kolmogorov-Smirnov test, Control vs. SD+Saline, p=0.819; SD+Saline vs. SD+GA, p=0.819. Saline, SD+Saline, SD+GA group, n=20 cells in 5 mice of each group. Control+GA group, n=10 cells in 4 mice. (C)The frequency of sEPSCs is decreased by SD and GA reversed this to control level. One-way ANOVA with Tukey’s multiple comparisons test. Control vs. SD+Saline, p =0.05; SD+Saline vs. SD+GA, p =0.04; Control vs. Control+GA, p=0.762. Control, SD+Saline, SD+GA group, n=20 cells in 5 mice of each group. Control+GA group, n=10 cells in 4 mice (D) Sample traces showing sIPSCs. (E, F) The inhibition synaptic transmission in pyramidal neurons is not affected by SD and GA. Amplitude: Kolmogorov-Smirnov test, Control vs. SD+Saline, p=0.847; SD+Saline vs. SD+GA, p=0.99. Frequency: one-way ANOVA with Tukey’s test. Control vs. SD+Saline, p=0.739; SD+Saline vs. SD+GA, p=0.996; Control vs. Control+GA, p=0.443. n=12 cells in 4 Control mice, n=12 cells in 4 SD+Saline mice, n=9 cells in 4 SD+GA mice, n=10 cells in 4 Control+GA mice. (G, H) The levels of MDA and the activity of SOD detected by spectrophotometric method. One-way ANOVA with Tukey’s test. MDA: Control vs. Control+SD, p=0.047; Control+SD vs. SD+GA, p<0.001. n=16 mice per group. SOD: Control vs. Control+SD, p<0.001; Control+SD vs. SD+GA, p<0.001. n=15 mice per group. (I) The expression of Nrf2 in the cortex detected by Elisa. One-way ANOVA with Tukey’s test. Control vs. Control+SD, p=0.049; Control+SD vs. SD+GA, p=0.005. n=a. All data are shown as mean±SEM. ***p<0.001, **p<0.01, *p<0.05, ns, not significant.

Fig 4: DEXA-treated BM-MSCs conditioned media decreased glucose uptake in hepatoma cells and reduced levels of hepatic inflammatory, angiogenic, and oxidative stress markers in mice. HepG2 cells treated with BM-MSC/DEXA-S significantly consumed less glucose compared with untreated control cells (P < 0.001) (A). Transfusion of BM-MSC-S in ALF mice variably reduced the inflammatory (TNF-α), and the angiogenic (VEGF) markers, and ameliorated the oxidative stress markers (Nrf2 and SOD) (C&D, respectively). Data are presented as mean (± SD)