Inhibitory Effect of Curcumol on Jak2-STAT Signal Pathway Molecules of Fibroblast-Like Synoviocytes in Patients with Rheumatoid Arthritis

Hyperplasia of synovial membrane in rheumatoid arthritis (RA) is a critical pathological foundation for inducing articular injury. The janus kinase and signal transducer and activator of transcription (Jak-STAT) pathway plays a critical role in synovial membrane proliferation induced by platelet-derived growth factor (PDGF). To explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant zedoary rhizome, the changes of Jak2-STAT1/3 signal pathway-related molecules in synoviocytes were observed in vitro. In this study, the fibroblast-like synoviocytes (FLS) in patients with RA were collected and cultured. The following parameters were measured: cell proliferation (WST-1 assay), cell cycles (fluorescence-activated cell sorting, FACS), STAT1 and STAT3 activities (electrophoretic mobility shift assay, EMSA), and the protein expressions of phosphorylated Jak2, STAT1, and STAT3 (Western blot). It was shown that curcumol could inhibit the RA-FLS proliferation and DNA synthesis induced by PDGF-BB in a dose-dependent manner in vitro. The transcription factors activities of STAT1 and STAT3 were obviously elevated after PDGF-BB stimulation (P < 0.05). Super-shift experiments identified the STAT1 or STAT3 proteins in the complex. Furthermore, the different concentration curcumol could downregulate the DNA binding activities of STAT1 and STAT3 (P < 0.05) and inhibit the phosphorylation of Jak2 while it had no effect on the protein expressions of STAT1 and STAT3. Positive correlations were found between changes of cell proliferation and DNA-binding activities of STAT1 and STAT3, respectively (P < 0.01). In conclusion, curcumol might suppress the FLS proliferation and DNA synthesis induced by PDGF-BB through attenuating Jak2 phosphorylation, downregulating STAT1 and STAT3 DNA-binding activities, which could provide theoretical foundation for clinical treatment of RA

CoFe nanoparticles dispersed in Co/Fe-N-C support with meso- and macroporous structures as the high-performance catalyst boosting the oxygen reduction reaction for Al/Mg-air batteries

Constructing the M-N-C (M = Fe, Co, etc.) with meso- and macroporous structures is an effective strategy for designing the high-performance catalysts towards oxygen reduction reaction (ORR). However, these structures can hardly be achieved via the pyrolysis of classic metal-organic frameworks. Herein, we prepare the CoFe nanoparticles with surface oxides dispersed in Co/Fe-N-C support via carbonizing melamine and ethylenediaminetetraacetic acid chelated with metal ions. This hybrid exhibits high proportions of meso- and macropores along with excellent ORR catalytic activity, as evidenced by the half-wave potentials of 0.91 and 0.61 V (vs. RHE) in 0.1 M KOH and 3.5 wt% NaCl, respectively. The Al/Mg-air batteries with this catalyst exhibit superior performance to those employing Pt/C, primarily derived from the enlarged pore diameters and the exposed ORR active sites substantially enhancing the air-electrode performance. Our study provides an avenue to broaden the pore sizes of M-N-C for boosting its ORR catalytic activity.•The hybrid catalyst composed of CoFe nanoparticles and Co/Fe-N-C support is prepared.•This hybrid has high ratios of meso- and macropores with exposed ORR active sites.•Excellent ORR catalytic activity is achieved due to the unique structure of hybrid.•The Al/Mg-air batteries with hybrid exhibit better performance than those with Pt/C