For a long time, how anti-inflammatory factors evolved was largely unknown. In this study, we chose a marine invertebrate, Litopenaeus vannamei, as a model and identified that shrimp mesencephalic astrocyte-derived neurotrophic factor (MANF) was an LPS-induced plasma protein, which exerted its anti-inflammatory roles on shrimp hemocytes by suppressing ERK phosphorylation and Dorsal expression. In addition, we demonstrated that shrimp MANF could be associated with a receptor protein tyrosine phosphatase (RPTP) to mediate negative regulation of ERK activation and Dorsal expression. More interestingly, shrimp RPTP-S overexpression in 293T cells could switch shrimp and human MANF-mediated ERK pathway activation to inhibition. In general, our results indicate that this conserved RPTP is the key component for extracellular MANF-mediated ERK pathway inhibition, which gives a possible explanation about why this neurotropic factor could both protect neuron cells from apoptosis and inhibit immune cell M1 activation in various species.
Due to the complexity of surgery for large-area bone injuries, implanting a large volume of materials into the injury site remains a big challenge in orthopedics. To solve this difficulty, in this study, a series of biomimetic hydroxyapatite/shape-memory composite scaffolds were designed and synthesized with programmable pore structures, based on poly(ε-caprolactone) (PCL), polytetrahydrofuran (PTMG) and the osteoconductive hydroxyapatite (HA). The obtained scaffolds presented various pore structures, high connectivity, tunable mechanical properties, and excellent shape memory performance. Moreover, the mineralization activity of the developed scaffolds could enhance the formation of hydroxyapatite and they showed good biocompatibility in vitro. The in vivo experiments show that scaffolds could promote the formation of new bone in critical size cranial defects. The programmable porous scaffold biomaterials exhibited potential application promise in bone regeneration.