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Guajadial, one of natural dialdehyde meroterpenoids, demonstrated significant antineoplasmic activity. The present research was to investigate the inhibitory effects of guajadial by using two NSCLC cells (A549 and H1650) proliferation and migration. Western blotting was employed to explore the underlying mechanisms of VEGF receptor (VEGFR)2-mediated. This research indicated that guajadial not only inhibited endothelial cell proliferation and migration but also suppress tumor growth in human NSCLC xenograft mouse models. It is also suggested that guajadial inhibited A549 proliferation via blocking the Ras/MAPK pathway. [ABSTRACT FROM AUTHOR]

Treating neuropathic pain continues to be a major clinical challenge and underlying mechanisms of neuropathic pain remain elusive. We have recently demonstrated that Wnt signaling, which is important in developmental processes of the nervous systems, plays critical roles in the development of neuropathic pain through the β-catenin-dependent pathway in the spinal cord and the β-catenin-independent pathway in primary sensory neurons after nerve injury. Here, we report that Wnt signaling may contribute to neuropathic pain through the atypical Wnt/Ryk signaling pathway in rats. Sciatic nerve injury causes a rapid-onset and long-lasting expression of Wnt3a, Wnt5b, and Ryk receptors in primary sensory neurons, and dorsal horn neurons and astrocytes. Spinal blocking of the Wnt/Ryk receptor signaling inhibits the induction and persistence of neuropathic pain without affecting normal pain sensitivity and locomotor activity. Blocking activation of the Ryk receptor with anti-Ryk antibody, in vivo or in vitro, greatly suppresses nerve injury-induced increased intracellular Ca and hyperexcitability of the sensory neurons, and also the enhanced plasticity of synapses between afferent C-fibers and the dorsal horn neurons, and activation of the NR2B receptor and the subsequent Ca-dependent signals CaMKII, Src, ERK, PKCγ, and CREB in sensory neurons and the spinal cord. These findings indicate a critical mechanism underlying the pathogenesis of neuropathic pain and suggest that targeting the Wnt/Ryk signaling may be an effective approach for treating neuropathic pain. [ABSTRACT FROM AUTHOR]