Analysis of Nano-ZnO-Modified Asphalt Compatibility Based on Molecular Dynamics.

Nano-ZnO has a large specific surface area, small particle size, and strong polarity and can be used as an additive to modify the base asphalt. In this paper, the compatibility mechanism between nano-ZnO modifier and asphalt is analyzed. Solubility parameters, interaction energNano-ZnO and mean square displacement of nano-ZnO in matrix asphalt were calculated at different temperatures to study the compatibility of the nano-ZnO modifier and the matrix asphalt. The radial distribution functions and radii of gyration of the asphalt's four components under the action of the nano-ZnO additive were calculated to investigate the effect of nano-ZnO on the molecular structure of the asphalt. The results show that the best compatibility between nano-ZnO and matrix asphalt is observed at 150 °C, especially when the nano-ZnO particle size was 6 Å. The particle sizes of nano-ZnO have little effect on the temperature at which the nano-ZnO-modified asphalt achieved its highest structural stability. Around 150 °C, the nano-ZnO-modified asphalt system with different particle sizes exhibit the highest stability and best compatibility. The addition of nano-ZnO improves the compactness of the asphalt structure and makes the asphalt more stable.

Inhibition of endothelin A receptor protects brain microvascular endothelial cells against hypoxia­induced injury.

Endothelin-1 (ET-1)-induced cell damage is commonly involved in ischemia/hypoxia-associated diseases. PD155080 [sodium 2-benzo (1.3)dioxol-5-yl-3-benzyl-4-(4­metho-xyphenyl)-4-oxobut-2-enoate] is a selective endothelin A receptor (ETAR) antagonist that inhibits ET-1­induced cell damage. The aim of this study was to investigate the effects of PD155080 on hypoxia-induced rat brain microvascular endothelial cell (BMEC) injury. BMECs were isolated from the cerebral cortex of Wistar rats and cultured in an anoxia chamber, containing 95% N(2) and 5% CO(2) for 12 h. BMEC injury was assessed by determining cellular ultra-microstructural changes and cell viability by MTT assay, trypan blue (TB) staining and measuring the lactate dehydrogenase (LDH) levels. ET-1 mRNA expression was detected by in situ hybridization and reverse transcription PCR (RT-PCR); the ET-1 protein level was measured by radioimmunoassay. Following exposure to hypoxic conditions, the viability of the BMECs was markedly decreased and the ultrastructure of the BMECs was damaged, as demonstrated by chromatin margination, chromatin agglutination, plasma edema, the increased number of intracellular liposomes and vacuoles, mitochondrial swelling and the expansion of a rough surfaced endoplasmic reticulum. The levels of ET-1 and ET-1 mRNA expression in the BMECs were increased following exposure to hypoxic conditions. Of note, the administration of PD155080 greatly enhanced the viability of the BMECs and ameliorated hypoxia-induced cellular injury. PD155080 also inhibited hypoxia-induced ET-1 production by the BMECs. In conclusion, PD155080 exerts protective effects against hypoxia-induced BMEC injury.

[SIRT1 expression and activity are up-regulated in the brain tissue of epileptic patients and rat models].

OBJECTIVE: To investigate the expression and activity of silent information regulator 1 (SIRT1) in the temporal lobe of epileptic patients and rat models and explore its role in the occurrence and progression of epilepsy. METHODS: The temporal lobe tissue of epileptic patients and rat models (induced by lithium-pilocarpine) were examined for SIRT1 expression using immunohistochemistry and Western blotting and also for SIRT1 activity using SIRT1 Deacetylase Assay Kit. RESULTS: Immunohistochemistry detected positive SIRT1 expression mainly in the cytoplasm of the neurons in both human and rat brains, and the epileptic groups showed stronger SIRT1 immunoreactivity than the control group. Western blotting and activity assay showed that the expression and activity of SIRT1 were significantly increased in the temporal lobe of patients with refractory epilepsy as compared with the tissues samples from non-epileptic patients (P<0.05). In the rat models of epilepsy, SIRT1 expression was up-regulated at 6, 24, and 72 h and at 7, 14, 30, and 60 days after kindling (P<0.05) and SIRT1 activity was significantly increased at 6, 24, and 72 h and at 7 and 14 days (P<0.05), with the peak level of SIRT1 expression and activity occurring at 72 h. CONCLUSION: Up-regulation of SIRT1 expression and activity in the temporal lobe of epileptic patients and rat models may play an important role in the pathogenesis of epilepsy.

Role of signal transducer and activator of transcription-3 in up-regulation of GFAP after epilepsy.

Glial Fibrillary Acidic Protein (GFAP) is regarded as a marker of reactive astrogliosis. Recent studies have demonstrated that signal transducer and activator of transcription-3, STAT3 regulates GFAP expression after brain injuries. However, whether STAT3 controls astrogliosis in epilepsy is not clear. In this study, we measured p-STAT3 and GFAP expression during the epileptic process using immunohistochemistry, Western blotting and immunofluorescence. Both p-STAT3 and GFAP expression were highly expressed in the rat hippocampus during different phases of the epileptic process. The augmentation of GFAP expression was inhibited by AG490, a janus kinase 2 (JAK2, an upstream gene of STAT3) inhibitor. The coexpression of p-STAT3 and GFAP was detected in the epileptic rat hippocampus and temporal neocortex of patients. These findings indicate that epilepsy involves the activation of STAT3 that up-regulates the expression of GFAP, which may play an important role in epileptogenesis.

Epileptiform discharge upregulates p-ERK1/2, growth-associated protein 43 and synaptophysin in cultured rat hippocampal neurons.

Extracellular signal-regulated protein kinase, ERK1/2 is activated by phosphorylation (p-ERK1/2) during environmental stress such as epileptiform discharge. We investigated the role of ERK1/2 in abnormal axon growth and synapse reorganization in cultured neurons displaying epileptiform activity. The cultured neurons displaying epileptiform activity were treated with magnesium-free extracellular fluid for 3h and monitored epileptiform discharges using whole-cell patch clamp. Two study groups, neurons displaying epileptiform activity and the same neurons treated with ERK1/2 inhibitor U0126, were studied at six time points, 0 min, 30 min, 2h, 6h, 12h, and 24h following discharge. The expressions of p-ERK1/2, C-fos, growth-associated protein 43 (GAP-43) and synaptophysin (SYP), as markers of axon growth and synapse reorganization, were investigated by double-label immunofluorescence and western blotting. In the neurons displaying epileptiform activity, p-ERK1/2 was detected immediately following discharge, and expression peaked at 30 min. The expression of C-fos, GAP-43 and SYP followed the same pattern as p-ERK1/2. In the treated group, p-ERK1/2 was inhibited completely, and C-fos, GAP-43 and SYP were reduced. These findings indicate that epileptiform discharge activates ERK1/2 which regulates C-fos in cultured neurons displaying epileptiform activity, and this cascade may upregulate GAP-43 and SYP to contribute to axon growth and synapse reorganization to potentiate epileptic activities.