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With an increasing understanding of the mechanisms of fracture healing, it has been found that nerve injury plays a crucial role in the process, but the specific mechanism is yet to be completely revealed. To address this issue and provide novel insights for fracture treatment, we compiled this review. This review aims to study the impact of nerve injury on fracture healing, exploring the role of neurotrophic factors in the healing process. We first revisited the effects of the central nervous system (CNS) and the peripheral nervous system (PNS) on the skeletal system, and further explained the phenomenon of significantly accelerated fracture healing under nerve injury conditions. Then, from the perspective of neurotrophic factors, we delved into the physiological functions and mechanisms of neurotrophic factors, such as nerve growth factor (NGF), Neuropeptides (NPs), and Brain-derived neurotrophic factor (BDNF), in bone metabolism. These effects include direct actions on bone cells, improvement of local blood supply, regulation of bone growth factors, control of cellular signaling pathways, promotion of callus formation and bone regeneration, and synergistic or antagonistic effects with other endocrine factors, such as Sema3A and Transforming Growth Factor β (TGF-β). Finally, we discussed the treatments of fractures with nerve injuries and the future research directions in this review, suggesting that the relationship between nerve injury and fracture healing, as well as the role of nerve injury in other skeletal diseases. • It summarized the impact of nerve injury on fracture healing and bone metabolism. • It introduced different ways in which nerve injury affects bone metabolism. • It revealed multiple signaling pathways regulated by neurotrophic factors. • It presented therapeutic approaches for nerve injury combined with fractures. [ABSTRACT FROM AUTHOR]

A tetrahydropyrrolidine analog YHR17, which was obtained using structural transformation and modification of 2- epi -jaspine B, inhibited SphK1 with more than 125-fold selectivity over SphK2. This analog demonstrated potent antiproliferative activities with IC 50 values ranging from 0.68 to 5.68 μM against tested cancer cell lines and inhibited proliferation of the A375 cell line by affecting cell cycle and apoptosis. • The structure-activity relationship of tetrahydropyrrolidine analogs was established. • YHR17 exhibited potent antiproliferative activities against tested cancer cell lines. • YHR17 has more than 125-fold selectivity for SphK1 over SphK2. 2- Epi -jaspine B is an isomer of the natural product jaspine B and shows certain selectivity for SphK1 and potent antitumor activity. Based on the crystal structure of SphK1, we transformed the structure of 2- epi -jaspine B and modified the hydrophobic side chain to obtain a series of 2- epi -jaspine B analogs. The MTT assay was used to examine the antitumor activities of these analogs. We identified a novel 2- epi -jaspine B analog YHR17 , which has potent antiproliferative activities for tested cell lines with IC 50 values that ranged from 0.68 to 5.68 μM and inhibited the proliferation of the A375 cell line by affecting the cell cycle and apoptosis. Furthermore, YHR17 inhibited SphK1 with more than 125-fold selectivity over SphK2. [ABSTRACT FROM AUTHOR]