ObjectiveValproic acid (VPA), as known as histone deacetylase inhibitor, has neuroprotective effects. This study investigated the histological changes and functional recovery from spinal cord injury (SCI) associated with VPA treatment in a rat model.MethodsLocomotor function was assessed according to the Basso-Beattie-Bresnahan scale for 2 weeks in rats after receiving twice daily intraperitoneal injections of 200 mg/kg VPA or the equivalent volume of normal saline for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation.ResultsBasso-Beattie-Bresnahan scale scores in rats receiving VPA were significantly higher than in the saline group (p<0.05). The cavity volume in the VPA group was significantly reduced compared with the control (saline-injected) group (p<0.05). The level of histone acetylation recovered in the VPA group, while it was significantly decreased in the control rats (p<0.05). The macrophage level was significantly decreased in the VPA group (p<0.05).ConclusionVPA influences the restoration of hyperacetylation and reduction of the inflammatory reaction resulting from SCI, and is effective for histology and motor function recovery.

A number of genes responsible for hearing loss are related to ion recycling and homeostasis in the inner ear. Connexins (Cx26 encoded by GJB2, Cx31 encoded by GJB3 and Cx30 encoded by GJB6) are core components of gap junctions in the inner ear. Gap junctions are intercellular communication channels and important factors that are associated with hearing loss. To date, a molecular genetics study of GJB3 and GJB6 as a causative gene for hearing loss has not been performed in Korea. This study was therefore performed to elucidate the genetic characteristics of Korean patients with nonsyndromic sensorineural hearing loss and to determine the pathological mechanism of hearing loss by analyzing the intercellular communication function of Cx30 and Cx31 variants. Sequencing analysis of the GJB3 and GJB6 genes in our population revealed a total of nine variants, including four novel variants in the two genes. Three of the novel variants (Cx31-p.V27M, Cx31-p.V43M and Cx-30-p.I248V) and two previously reported variants (Cx31-p.V84I and Cx30-p.A40V) were selected for functional studies using a pathogenicity prediction program and assessed for whether the mutations were located in a conserved region of the protein. The results of biochemical and ionic coupling tests showed that both the Cx31-p.V27M and Cx31-p.V84I variants did not function normally when each was expressed as a heterozygote with the wild-type Cx31. This study demonstrated that two variants of Cx31 were pathogenic mutations with deleterious effect. This information will be valuable in understanding the pathogenic role of GJB3 and GJB6 mutations associated with hearing loss.

Hemorrhagic stroke is a leading cause of death. The causes of intracerebral hemorrhage (ICH)-induced brain damage are thought to include lysis of red blood cells, hemin release and iron overload. These mechanisms, however, have not proven very amenable to therapeutic intervention, and so other mechanistic targets are being sought. Here we report that accumulation of endogenously formed zinc protoporphyrin (ZnPP) also critically contributes to ICH-induced brain damage. ICH caused a significant accumulation of ZnPP in brain tissue surrounding hematoma, as evidenced by fluorescence microscopy of ZnPP, and further confirmed by fluorescence spectroscopy and supercritical fluid chromatography-mass spectrometry. ZnPP formation was dependent upon both ICH-induced hypoxia and an increase in free zinc accumulation. Notably, inhibiting ferrochelatase, which catalyzes insertion of zinc into protoporphyrin, greatly decreased ICH-induced endogenous ZnPP generation. Moreover, a significant decrease in brain damage was observed upon ferrochelatase inhibition, suggesting that endogenous ZnPP contributes to the damage in ICH. Our findings reveal a novel mechanism of ICH-induced brain damage through ferrochelatase-mediated formation of ZnPP in ICH tissue. Since ferrochelatase can be readily inhibited by small molecules, such as protein kinase inhibitors, this may provide a promising new and druggable target for ICH therapy.

Human health is seriously threatened by mycotoxin contamination, yet health risk assessments are typically based on just one mycotoxin, potentially excluding the additive or competitive interactions between co-occurring mycotoxins. In this investigation, we evaluated the individual or combined toxicological effects of three fumonisin-family B mycotoxins: fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3), by using porcine intestinal epithelial cells (IPEC). IPEC cells were exposed to various concentrations (2.5–40 μM) for 48 h, and a cell counting kit (CCK8) was used to determine cell vitality. Firstly, we discovered that they might inhibit cell viability. Additionally, the cytotoxicity of FB1 was significantly greater than that of FB2 and FB3. The results also indicated that the combinations of FB1-FB2, FB2-FB3, and FB1-FB2-FB3 showed synergistically toxicological effects at the ID10-ID50 levels and antagonistic effects at the ID75-ID90 levels. In addition, the FB1-FB3 exposure was also synergistic at the ID10-ID25 level. We also found that myriocin and resveratrol alleviated the cytotoxicity induced by fumonisin in IPEC cells. In all, this study may contribute to the determination of legal limits, the optimization of risk assessment for fumonisins in food and feed, and the development of new methods to alleviate fumonisin toxicity.