International journal of molecular medicine
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The aim of the present study was to investigate the role of complement activation in the pathogenesis of neuropathic pain (NPP) induced by peripheral nerve injury. We modified a classical chronic constriction injury (CCI) model (mCCI), and verified its reliability in rats. Furthermore, reverse transcription-PCR and immunohistochemistry were conducted to investigate complement activation in the spinal dorsal horn and the effect of a complement inhibitor, cobra venom factor (CVF), on the behavior of the mCCI model rats. ⋯ Transmission electron micrographs revealed mitochondrial swelling, cell membrane damage, and cristae fragmentation in the neurons of the spinal dorsal horn 14 days after mCCI. Mitochondrial swelling was attenuated in mCCI rats receiving CVF. The findings demonstrated that abnormal complement activation occurred in the dorsal horn of the spinal cord in rats with NPP, and C3 in the spinal dorsal horn could play an important role in the cascade reaction of complements that are involved in the development of hyperalgesia.
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The pharmacologically-induced expression of the γ-globin gene, to increase fetal hemoglobin (HbF) production, is a therapeutic strategy used for the treatment of β-thalassemia and sickle cell anemia (SCA). The aim of this study was to investigate the effects of Plastrum testudinis (PT) on differentiation, proliferation, γ-globin gene expression and HbF synthesis in human erythroid cells. For this purpose, we used the K562 human leukemia cell line and human erythroid progenitor cells from normal donors and patients with β-thalassemia cultured using the two-phase liquid culture system. ⋯ These effects were suppressed by pre-treatment with the p38 MAPK inhibitor, SB203580. Epigenetic histone modifications within γ-globin gene promoter regions, via activation of the p38 MAPK signaling pathway, are important for the induction of γ-globin gene expression in human erythroid cells by PT. PT may be a novel potential therapeutic agent for β-hemoglobinopathies, including β-thalassemia and SCA.