Fig 2: Effect of Au NPs@polyphenols on the Ca2+ level in SH-SY5Y (a) and MCF-7 (b) cells after 24 h and 48 h of exposure to two doses (c1 and c2) of Au NPs@polyphenols at 37 °C and 43 °C, following the procedure described in the section, Materials. The data are reported as the mean ± SD from three independent experiments; * p < 0.05, compared with control (n = 8). (c,d) The effect of Au NPs@polyphenols on the ROS level in SH-SY5Y and MCF-7 cells after 24 h and 48 h of exposure to two doses (c1 and c2) of Au NPs@polyphenols at 37 °C and 43 °C, following the procedure described in the section, Materials. The ROS generation of NP-treated cells is expressed relative to non-treated control cells. As a positive control (P), the cells were incubated with 500 μM of H2O2, showing a ca. 300% DCFH-DA increase (not shown). The data are reported as the mean ± SD from three independent experimens; * p < 0.05, compared with the control (n = 8). (e–l) Representative fluorescence images of SH-SY-5Y and MCF-7 cells exposed to the c2 of Au NPs@polyphenols at 37 °C and 43 °C, following the procedure described in the section, Materials. (m) ELISA quantitative analyses of HSP70 in SH-SY5Y and MCF-7 cells treated with Au NPs@polyphenols at 37 °C and 43 °C at the c2 concentration, following the procedure described in the section, Materials. Histogram showing the levels of HSP70 expressed in ng/mL in SH-SY5Y (n) and MCF-7. The data are presented as the mean ± standard deviation of three independent experiments: * p < 0.05.

Fig 3: Sevoflurane exposure induced cognitive impairment and suppressed Hsp70 protein levels in aged mice. (a–d) Spatial learning and memory of aged mice were determined by the Morris water maze. Escape latencies (a) and average speed of swimming (b) were recorded in the three training sessions. The duration in the target quadrant (c) and the number of times crossing the platform site during the probe trial were recorded. The Hsp70 concentrations in plasma (e) and (f) were determined in mice at 48 h after sevoflurane anesthesia with different concentrations for 3 h. Twelve mice were used for each group. Data were represented by mean ± SD. *p < .05, **p < .01, ***p < .001

Fig 4: Exogenous rHsp70 restored Hsp70 expressions in aged mice under sevoflurane anesthesia. Enzyme‐linked immunosorbent assay (ELISA) was used to measure the Hsp70 levels in serum (a) and hippocampus (b). Quantitative reverse transcription polymerase chain reaction (RT‐qPCR) was used to measure the mRNA expression of Hsp70 in the hippocampus (c). Hippocampal Hsp70 protein expression was determined by Western blot analysis (d). Twelve mice were used for each group. For the experiments of RT‐qPCR and Western blotting, the hippocampal homogenate from 12 mice in each group was mixed, and the experiments were repeated for four times. Data were represented by mean ± SD. *p < .05, **p < .01, ***p < .001

Fig 5: Blockade of Nav1.7 regulates chondrocyte biology through enhancing HSP70 and midkine secretion.a, Peptide-spectrum match (PSM)-based abundance of proteins identified from the 30–100 kDa fraction of conditioned medium that are unique to (red dots) or increased with (blue dots) PF-04856264 and ProTx II treatment. b, PSM-based abundance of proteins (red dot) identified from the 10–30 kDa fraction of conditioned medium that are unique to PF-04856264 and ProTx II treatment. c, COL2 and ACAN mRNA levels in human C28I2 chondrocytes stimulated with conditioned medium collected from cells treated with ProTx II (Pro-CM) or PF-04856264 (PF-CM) in the absence or presence of IgG or anti-HSP70 antibodies (n = 4 biological replicates). d, MMP13 and ADAMTS5 mRNA levels in C28I2 chondrocytes stimulated with IL-1β and conditioned medium collected from cells treated with ProTx II (Pro-CM) or PF-04856264 (PF-CM) in the absence or presence of control IgG or anti-midkine antibodies (n = 4 biological replicates). e, Safranin O and Fast Green-stained knee joint sections (n = 8). Ver, VER 155008. Scale bar, 50 µm. f, OARSI score from images represented in e. g, Two-minute travel distance and von Frey testing at the indicated time points with indicated treatments after DMM surgery (n = 8). Data are mean ± 95% confidence interval, P values by two-way ANOVA with Bonferroni post hoc test. *Vehicle versus PF, P < 0.05; **vehicle versus PF, P < 0.01; #PF versus PF + Ver + iMDK, P < 0.05; ##PF versus PF + Ver + iMDK, P < 0.01. c,d,f, Data are mean ± s.d., P values by one way ANOVA with Bonferroni post hoc test.Source Data