Traumatic brain injury (TBI) is one of the major causes of mortality and disability for all ages worldwide. Mesenchymal stem cells (MSCs)-originated exosomes have provided therapeutic effects. However, as an indispensable component of MSCs, whether odontogenic stem cell-generated exosomes could benefit TBI is still unclear. Thus we aimed to explore the potential of stem cells from human exfoliated deciduous teeth-originated exosomes (SHED-Ex) for the management of TBI. First, a transwell system was used to co-culture activated BV-2 microglia cells with SHED. The secretion levels of neuroinflammatory factors and nitrite were evaluated by enzyme-linked immunosorbent assay (ELISA) and Griess assay. Furthermore, purified SHED-Ex were co-cultured with activated BV-2. ELISA, Griess assay, flow cytometry, immunofluorescence, and qRT-PCR were performed to test the levels of inflammatory factors as well as the microglia phenotype. Finally, SHED and SHED-Ex were locally injected into TBI rat models. Basso, Beattie, and Bresnahan (BBB) scores were chosen to evaluate the motor functional recovery. Histopathology and immunofluorescence were performed to measure the lesion volume and neuroinflammation. As a result, SHED-Ex could reduce neuroinflammation by shifting microglia polarization. The administration of SHED-Ex improves rat motor functional recovery and reduces cortical lesion compared with the control group 2 weeks post-injury (P < 0.05). The current study demonstrates for the first time that SHED-Ex contribute a therapeutic benefit to TBI in rats, at least in part by shifting microglia polarization to reduce neuroinflammation. The use of odontogenic stem cells, and indeed their exosomes, may be expanded for the treatment of TBI or other neurological disorders.

The cross-talk between RNA binding proteins (RBPs) and microRNAs (miRNAs) in the regulation of gene expression is a complex process. Here, we describe a new mode of regulation of TRIM25 expression mediated by an antagonistic interplay between IGF2BP3 and miR-3614-3p. The expression level of TRIM25, IGF2BP3, pri-miR-3614 and miR-3614-3p in breast cancer (BC) tissues, non-tumor tissues and BC cell lines were detected by qRT-PCR, Western blot and Immunohistochemistry (IHC). Binding of miR-3614-3p and IGF2BP3 to TRIM25 RNA was verified using luciferase activation assays, RNA immunoprecipitation (RIP) and biotin pull-down assays. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and related mechanism of IGF2BP3-miR-3614-3p-TRIM25 axis in in breast cancer cells proliferation. We found that an intragenic miRNA-3614-3p inhibits the expression of its host gene TRIM25 by binding to its 3'- untranslated region (UTR). Interestingly, IGF2BP3 can competitively occupy this binding site and inhibit miRNA-3614 maturation, thereby protecting TRIM25 mRNA from miR-3614-mediated degradation. The overexpression of miR-3614-3p dramatically inhibited breast cancer cell growth through the downregulation of TRIM25. Furthermore, the silencing of IGF2BP3 reduced TRIM25 expression, suppressed cell proliferation, and exhibited a synergistic effect with miR-3614-3p overexpression. Collectively, these results demonstrate that control of TRIM25 RNA by an interplay between IGF2BP3 and miR-3614-3p represents a mechanism for breast cancer cell proliferation. FUND: The scientific research and sharing platform construction project of Shaanxi Province, Opening Project of Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, China Postdoctoral Science Foundation and The National Natural Science Foundation of China.