Recent advances in the molecular mechanisms of low-intensity pulsed ultrasound against inflammation.

Low-intensity pulsed ultrasound (LIPUS), as a safe and potent physical therapy, has been widely used. It has been demonstrated that LIPUS could induce multiple biological effects, such as relieving pain, accelerating tissue repair/regeneration, and alleviating inflammation. A number of in vitro studies have indicated that LIPUS could significantly reduce the expression of proinflammatory cytokines. This anti-inflammatory effect has also been verified in many in vivo researches. However, the molecular mechanisms underlying LIPUS against inflammation are far from fully elucidated and may differ among different tissues and cells. Here, we review the applications of LIPUS against inflammation through different signaling pathways including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and phosphatidylinositol-3-kinase/serine/threonine kinase (PI3K/Akt), and discuss the underlying mechanisms. The positive effects of LIPUS on exosomes against inflammation and related signaling pathways are also discussed. A systematic overview of recent advances will present a deeper understanding of the molecular mechanisms of LIPUS, thus boosting our ability to optimize this promising anti-inflammatory therapy.