The Stem Cell Potential of O-2A Lineage Astroglia.

Astrocytes are the most common glial type in the central nervous system. They play pivotal roles in neurophysiological and neuropathological processes. Mounting evidence indicates that astrocytes may act as neural stem cells and contribute to adult neurogenesis. In previous reports, freshly isolated O-2A progenitors were shown to revert to neural stem-like cells (NSLCs) when cultured with a serum-containing glial medium or bone morphogenic proteins for 3 days and with basic fibroblast growth factor consecutively. NSLCs possess self-renewal and multipotential capacities that can give rise to neurons and glial cells, which suggests that they have stem cell-like properties. However, the underlying molecular mechanisms and cell fate commitment when exposed to a neural conditioned medium remain obscure. In this study, we demonstrated that NSLCs grown in the serum-containing neurobasal medium can differentiate into induced neural-like cells (iNLCs). It was noteworthy that astroglia mixed in these cells, particularly in iNLCs, were gradually replaced by neural phenotypes during this glia-neuron conversion. Remarkably, these glial cells can maintain high levels of proliferation and self-renewal ability by activating the NF-κB and MAPK signals. Finally, we found that Notch, STAT3, autophagy, bHLH, and Wnt signals appear to be critical modulators of these intricate events. Altogether, these data demonstrate that O-2A lineage astroglia can function as neural stem cells and display neurogenic plasticity. Dissecting the regulatory pathways involved in these processes is essential to the understanding of glial cell fate and its precise functions. This finding may foster a better understanding of astrocytic heterogeneity and lead to innovative ways to readily apply stem-like astroglia cells as candidate cell sources for neural repair.

Effect of "phase change" complex on postoperative adhesion prevention.

BACKGROUND: Postsurgical peritoneal adhesion is a major clinical problem. Numerous anti-adhesion products have been studied, but none could be easily used to provide a physical barrier. In this study, we developed a "phase change" anti-adhesion barrier for reducing peritoneal adhesion by cross-linked copolymerization of O-carboxymethyl chitosan (CMC) and CaCl2 and addition of cyclosporin A (CsA). MATERIALS AND METHODS: The CMC-CaCl2-CsA compound was characterized by equilibrium swelling rate, weight loss, releasing effect, and coagulation test, and its biosafety was characterized by acute oral toxicity, hemolysis, and cytotoxicity. Intestinal adhesion model was applied on 64 Sprague-Dawley rats, which received CMC, CMC-CaCl2, or CMC-CaCl2-CsA treatment. At postoperative days 7 and 14, the rats were euthanized, and adhesions were graded by an investigator blinded to the treatment groups, using a predetermined adhesion scoring system. The cecum and adhesion tissue were stained with hematoxylin and eosin and antibodies for matrix metalloproteinase-9 and TIMP-1 for further histopathologic examination. RESULTS: The phase change anti-adhesive material exhibited effective blood clotting and were nontoxic in clotting experiments and acute toxicity test. The degradation rate could be adjusted using phosphate-buffered solution with varying pH. Adhesions were significantly reduced in the CMC-CaCl2-CsA treatment group compared with the control group (P < 0.001). Expression of matrix metalloproteinase-9 was stronger in CMC-CaCl2-CsA treatment group at 7 days after surgery. CONCLUSIONS: "Phase-change" adhesive can undergo changes after application, and it inhibits the formation of abdominal adhesions after surgery. The material is convenient for using by surgeons and provides an effective tool for intestinal adhesion prevention.

Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop.

Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca(2+) concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

Conformational flexibility of beta-secretase: molecular dynamics simulation and essential dynamics analysis.

AIM: Based on the structural analysis to reveal the mechanism of ligand binding to beta-secretase and the specificity of each binding sub-site. METHODS: Molecular dynamics was used to simulate on the ligand free beta-secretase and ligand bound beta-secretase. The trajectories were analyzed using the essential dynamics, and the significant conformational change was illustrated employing the DynDom program. RESULTS: The essential dynamics and DynDom analyses clearly showed that the beta-secretase experienced a large conformational change upon the substrate or inhibitor binding. The flap structure adopted a swing motion, gradually covering the active site to facilitate the ligand binding process. Residues Ser86 and Ile87 served as the hinge point. Inhibitor-enzyme interaction analysis revealed that residues at P2, P1, and P1' positions of the inhibitor were very important for the binding, and residues at P2' and P3' positions may be modified to improve the binding specificity. S3 subsite of the enzyme still had space to modify the inhibitors in increasing the binding affinity. CONCLUSION: The information presented here is valuable and could be used to identify small molecular inhibitors of beta-secretase.