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Background: Antimicrobial macin proteins aggregate bacteria and exert nerve repair activities. Results: Structures of theromacin and neuromacin were elucidated. Nerve repair activities and antimicrobial activities of macins were investigated. Conclusion: Theromacin induces the nerve repair capacity of leech plasma. Macins seem to be proliferation factors. Significance: The extended magnitude of macin activities demands reconsidering their potential biological impact on nerve repair/neurons in their hosts.

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Neuroblastoma is a malignant childhood cancer arising from the embryonic sympathoadrenal lineage of the neural crest. Retinoic acid (RA) is included in the multimodal therapy of patients with high‐risk neuroblastoma to eliminate minimal residual disease. However, the formation of RA‐resistant cells substantially lowers 5‐year overall survival rates. To examine mechanisms that lead to treatment failure, we chose human SH‐SY5Y cells, which are known to tolerate incubation with RA by activating the survival kinases Akt and extracellular signal‐regulated kinase 1/2. Characterization of downstream pathways showed that both kinases increased the phosphorylation of the ubiquitin ligase mouse double minute homolog 2 (Mdm2) and thereby enhanced p53 degradation. When p53 signaling was sustained by blocking complex formation with Mdm2 or enhancing c‐Jun N‐terminal kinase (JNK) activation, cell viability was significantly reduced. In addition, Akt‐mediated phosphorylation of the cell‐cycle regulator p21 stimulated complex formation with caspase‐3, which also contributed to cell protection. Thus, treatment with RA augmented survival signaling and attenuated basal apoptotic pathways in SH‐SY5Y cells, which increased cell viability.