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In order to guide a reasonable application of the bulk ultrafine-grained industrial pure iron, a serious of ultrafine-grained pure iron samples with different microstructures were fabricated by multi-passes ECAP and heat-treatment, and their microstructures and pitting corrosion behaviour were investigated by transmission electron microscopy (TEM), electrochemical polarization and impedance spectroscopy (EIS) techniques, respectively. Results show that:with the increase of ECAP passes, lath-shaped structure with high dislocation density transforms into equiaxed grains with low dislocation density; the dislocation density decreases and the high-angle grain boundaries increase, after the annealing treatment. ECAP passes have less effect on the self-passivation of pure iron, and its open circuit potential (OCP) and polarization resistance are less changed; the pitting corrosion resistance of the ECAPed pure iron is related to the ECAP passes:the pitting potential first decreases and then increases with the increase of ECAP passes; the self-passivation property and pitting corrosion resistance of the ECAPed pure iron are improved after the annealing heat-treatment, the OCP, polarization resistance and pitting potential values increase obviously.

Abstract Background The bark of magnolia has been used in Oriental medicine to treat a variety of remedies, including some neurological disorders. Magnolol (Mag) and honokiol (Hon) are isomers of polyphenolic compounds from the bark of Magnolia officinalis, and have been identified as major active components exhibiting anti-oxidative, anti-inflammatory, and neuroprotective effects. In this study, we investigate the ability of these isomers to suppress oxidative stress in neurons stimulated by the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) and oxidative and inflammatory responses in microglial cells activated by interferon-γ (IFNγ) and lipopolysaccharide (LPS). We also attempt to elucidate the mechanism and signaling pathways involved in cytokine-induced production of reactive oxygen species (ROS) in microglial cells. Methods Dihydroethidium (DHE) was used to assay superoxide production in neurons, while CM-H2DCF-DA was used to test for ROS production in murine (BV-2) and rat (HAPI) immortalized microglial cells. NADPH oxidase inhibitors (for example, diphenyleneiodonium (DPI), AEBSF, and apocynin) and immunocytochemistry targeting p47phox and gp91phox were used to assess the involvement of NADPH oxidase. Western blotting was used to assess iNOS and ERK1/2 expression, and the Griess reaction protocol was employed to determine nitric oxide (NO) concentration. Results Exposure of Hon and Mag (1–10 μM) to neurons for 24 h did not alter neuronal viability, but both compounds (10 μM) inhibited NMDA-stimulated superoxide production, a pathway known to involve NADPH oxidase. In microglial cells, Hon and Mag inhibited IFNγ±LPS-induced iNOS expression, NO, and ROS production. Studies with inhibitors and immunocytochemical assay further demonstrated the important role of IFNγ activating the NADPH oxidase through the p-ERK-dependent pathway. Hon and, to a lesser extent, Mag inhibited IFNγ-induced p-ERK1/2 and its downstream pathway for ROS and NO production. Conclusion This study highlights the important role of NADPH oxidase in mediating oxidative stress in neurons and microglial cells and has unveiled the role of IFNγ in stimulating the MAPK/ERK1/2 signaling pathway for activation of NADPH oxidase in microglial cells. Hon and Mag offer anti-oxidative or anti-inflammatory effects, at least in part, through suppressing IFNγ-induced p-ERK1/2 and its downstream pathway.

Abstract Background Amyotrophic lateral sclerosis (ALS) is a disease affecting the central nervous system that is either sporadic or familial origin and causing the death of motor neurons. One of the genetic factors contributing to the etiology of ALS is mutant SOD1 (mtSOD1), which induces vulnerability of motor neurons through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport, glutamate excitotoxicity, inadequate growth factor signaling, and neuroinflammation. Bee venom has been used in the practice of Oriental medicine and evidence from the literature indicates that BV plays an anti-inflammatory or anti-nociceptive role against inflammatory reactions associated with arthritis and other inflammatory diseases. The purpose of the present study was to determine whether bee venom suppresses motor neuron loss and microglial cell activation in hSOD1G93A mutant mice. Methods Bee venom (BV) was bilaterally injected (subcutaneously) into a 14-week-old (98 day old) male hSOD1G93A animal model at the Zusanli (ST36) acupoint, which is known to mediate an anti-inflammatory effect. For measurement of motor activity, rotarod test was performed and survival statistics were analyzed by Kaplan-Meier survival curves. The effects of BV treatment on anti-neuroinflammation of hSOD1G93A mice were assessed via immunoreactions using Iba 1 as a microglia marker and TNF-α antibody. Activation of ERK, Akt, p38 MAP Kinase (MAPK), and caspase 3 proteins was evaluated by western blotting. Results BV-treated mutant hSOD1 transgenic mice showed a decrease in the expression levels of microglia marker and phospho-p38 MAPK in the spinal cord and brainstem. Interestingly, treatment of BV in symptomatic ALS animals improved motor activity and the median survival of the BV-treated group (139 ± 3.5 days) was 18% greater than control group (117 ± 3.1 days). Furthermore, we found that BV suppressed caspase-3 activity and blocked the defects of mitochondrial structure and cristae morphology in the lumbar spinal cord of hSOD1G93A mice at the symptomatic stage. Conclusion From these findings, our research suggests BV could be a potential therapeutic agent for anti-neuroinflammatory effects in an animal model of ALS.

Lipopolysaccharide binding protein (LBP) has been reported to be associated with prognosis in colorectal carcinoma and renal cell carcinoma; however, the clinical significance of LBP in human primary hepatocellular carcinoma (HCC) is inconclusive. We aimed to investigate the clinical significance and prognostic value of LBP in human primary HCC. In the present study, 346 patients with HCC who underwent curative resection were retrospectively analyzed. LBP protein expression was evaluated using western blot analysis and immunohistochemistry. LBP scores collected from immunohistochemical analysis were obtained by multiplying staining intensity and the percentage of positive cells. An outcome-based best cutoff-point was calculated by X-tile software. Moreover, Kaplan-Meier curves and Cox regressions were used for prognosis evaluation. LBP was frequently overexpressed in HCC compared with that in peritumor tissues (five pairs by western blot analysis, P=0.0533; 77 pairs by immunohistochemistry, P=0.0171), and LBP expression was positively associated with tumor-node-metastasis stage and tumor differentiation. Patients who had high LBP expression had decreased overall survival and time to recurrence compared with patients with low LBP expression. Furthermore, patients who were both serum α-fetoprotein positive and had high LBP expression had poor prognoses. Univariate and multivariate Cox analyses indicated that this combination was an independent prognostic factor [overall survival: Hazard ratio (HR), 1.458; 95% confidence interval (CI), 1.158–1.837; P=0.001; time to recurrence: HR,1.382; 95% Cl, 1.124–1.700; P=0.002]. In conclusion, LBP is highly expressed in HCC, and high LBP expression combined with serum α-fetoprotein may predict poor outcomes in patients with HCC following curative resection. [ABSTRACT FROM AUTHOR]