Nerve growth factor(Amgen, Inc.)

The fundamental issue of osteoporosis (OP) is osteoblast decrease due to oxidative stress and the subsequent disruption of the osteogenic and osteoclastic dynamic balance. How to promote the proliferation and osteogenic differentiation of osteoblast precursor cells (MC3T3-E1) in an oxidative microenvironment is a great challenge for improving OP. In this study, Prussian blue nanoparticles (PB NPs) were initially functionalized with a polydopamine (PDA) coating. Nerve growth factor (NGF) was subsequently immobilized on the PDA layer, followed by the hybrid membrane coating composed of red blood cell membrane (RBCm) and MC3T3-E1 cell membrane (MC3T3m), thereby constructing a biomimetic Prussian blue nanocomplex loaded with NGF (MPDN NPs). In vitro studies have shown that the nanodrug restored the impaired proliferation viability of MC3T3-E1 cells and inhibit their apoptosis by scavenging reactive oxygen species (ROS), and further cooperate with NGF to promote osteogenic differentiation. In vivo studies have demonstrated that the nanodrug significantly inhibited bone loss and promote bone regeneration in osteoporotic mice. Moreover, this nanodrug with excellent safety both in vitro and in vivo showed the long half-life in the bloodstream and high accumulation in the bone. In summary, this strategy addresses the fundamental issue of decreased osteoblast in OP and offers a novel approach for preventing and treating OP.

Repetitive transcranial magnetic stimulation (rTMS) has shown promise as an intervention for pain. An unexplored research question is whether the delivery of rTMS prior to pain onset might protect against a future episode of prolonged pain. The present study aimed to determine whether (1) 5 consecutive days of rTMS delivered prior to experimentally induced prolonged jaw pain has a prophylactic effect on future pain intensity and (2) whether these effects were accompanied by increases in corticomotor excitability (CME) and/or sensorimotor peak alpha frequency (PAF). On each day from day 0 to 4, 40 healthy individuals received a single session of active (n = 21) or sham (n = 19) rTMS over the left primary motor cortex. Peak alpha frequency and CME were assessed on day 0 (before rTMS) and day 4 (after rTMS). Prolonged pain was induced via intramuscular injection of nerve growth factor in the right masseter muscle after the final rTMS session. From days 5 to 25, participants completed twice-daily electronic diaries including pain on chewing and yawning (primary outcomes), as well as pain during other activities (eg, talking), functional limitation in jaw function and muscle soreness (secondary outcomes). Compared to sham, individuals who received active rTMS subsequently experienced lower pain on chewing and yawning. Furthermore, active rTMS led to an increase in PAF. This is the first study to show that rTMS delivered prior to prolonged pain onset can protect against future pain. Our findings suggest that rTMS may hold promise as a prophylactic intervention for pain.