BackgroundPrevious studies have demonstrates that, after nerve injury, extracellular signal-regulated protein kinase (ERK) activation in the spinal cord-initially in neurons, then microglia, and finally astrocytes. In addition, phosphorylation of ERK (p-ERK) contributes to nociceptive responses following inflammation and/or nerve injury. However, the role of spinal cells and the ERK/MAPK pathway in cancer-induced bone pain (CIBP) remains poorly understood. The present study analyzed activation of spinal cells and the ERK/MAPK pathway in a rat model of bone cancer pain.ResultsA Sprague Dawley rat model of bone cancer pain was established and the model was evaluated by a series of tests. Moreover, fluorocitrate (reversible glial metabolic inhibitor) and U0126 (a MEK inhibitor) was administered intrathecally. Western blots and double immunofluorescence were used to detect the expression and location of phosphorylation of ERK (p-ERK). Our studies on pain behavior show that the time between day 6 and day 18 is a reasonable period ("time window" as the remaining stages) to investigate bone cancer pain mechanisms and to research analgesic drugs. Double-labeling immunofluorescence revealed that p-ERK was sequentially expressed in neurons, microglia, and astrocytes in the L4-5 superficial spinal cord following inoculation of Walker 256 cells. Phosphorylation of ERK (p-ERK) and the transcription factor cAMP response element-binding protein (p-CREB) increased in the spinal cord of CIBP rats, which was attenuated by intrathecal injection of fluorocitrate or U0126.ConclusionsThe ERK inhibitors could have a useful role in CIBP management, because the same target is expressed in various cells at different times.

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The purpose of the present study was to investigate the role of autophagy on rat bone marrow mesenchymal stem cell (BMSC) proliferation, apoptosis and differentiation into neurons. After treatment with rapamycin, 3-methyladenine (3-MA) or chloroquine, the cell cycle, apoptosis, expression of neuron-specific enolase (NSE) and the mean fluorescence intensity (MFI) of Notch1 in BMSCs were examined by flow cytometry. The expression of microtubule-associated protein 2 (MAP2), Notch1 and Hes1 was investigated by western blot analysis. The results showed that after induction of autophagy using rapamycin, the proliferation of BMSCs was inhibited. Furthermore, the S-phase population was significantly decreased compared to that in the control group (P<0.05). In addition, the percentage of NSE-positive cells and the expression of MAP2 were significantly increased compared to those in the control group (P<0.05). The MFI of Notch1 was markedly upregulated compared to that in the control group (P<0.05). When autophagy was inhibited by 3-MA or chloroquine, the percentage of apoptotic cells and NSE-positive cells as well as the expression of MAP2 were markedly reduced compared to those in the control group (P<0.05). Furthermore, western blot analysis showed that Notch1 and Hes1 were decreased in the rapamycin-treated group, while they were not affected by 3-MA or chloroquine. The present study indicated that induction of autophagy in BMSCs decreased their S-phase population, promoted their differentiation into neurons and promoted the expression of NSE and MAP2. The mechanisms underlying this process may be linked to the regulation of autophagy-induced inhibition of the Notch1 signaling pathway.

Extensive use of fossil fuels can lead to energy depletion and serious environmental pollution. Therefore, it is necessary to solve these problems by developing clean energy. Graphene materials own the advantages of high electrocatalytic activity, high conductivity, excellent mechanical strength, strong flexibility, large specific surface area and light weight, thus giving the potential to store electric charge, ions or hydrogen. Graphene-based nanocomposites have become new research hotspots in the field of energy storage and conversion, such as in fuel cells, lithium-ion batteries, solar cells and thermoelectric conversion. Graphene as a catalyst carrier of hydrogen fuel cells has been further modified to obtain higher and more uniform metal dispersion, hence improving the electrocatalyst activity. Moreover, it can complement the network of electroactive materials to buffer the change of electrode volume and prevent the breakage and aggregation of electrode materials, and graphene oxide is also used as a cheap and sustainable proton exchange membrane. In lithium-ion batteries, substituting heteroatoms for carbon atoms in graphene composite electrodes can produce defects on the graphitized surface which have a good reversible specific capacity and increased energy and power densities. In solar cells, the performance of the interface and junction is enhanced by using a few layers of graphene-based composites and more electron-hole pairs are collected; therefore, the conversion efficiency is increased. Graphene has a high Seebeck coefficient, and therefore, it is a potential thermoelectric material. In this paper, we review the latest progress in the synthesis, characterization, evaluation and properties of graphene-based composites and their practical applications in fuel cells, lithium-ion batteries, solar cells and thermoelectric conversion.