To evaluate the effects of dexmedetomidine (Dex) and oxycodone (Oxy) on neurocognitive and inflammatory response after tourniquet-induced ischemia–reperfusion (I/R) injury. C57/BL6 mice were used to construct the mouse model of tourniquet-induced I/R injury. Mice (n?=?48) were randomly divided into sham, I/R, Dex or Oxy group. Morris water maze test was performed to assess the spatial learning and memory function. The expression of NF-κB, TLR4, NR2B, M1 (CD68 and TNF-α) and M2 (CD206 and IL-10) polarization markers in mice hippocampus were detected by western blot or immunofluorescent staining. Spontaneous excitatory post-synaptic currents (sEPSCs) were recorded by electrophysiology. Dex treatment alleviated I/R-induced declines in learning and memory (p < 0.05), while Oxy had no significant effect on it. Compared with I/R group, Dex and Oxy treatment down-regulated the expression of NF-κB, TLR4, TNF-α and CD68 (all p < 0.05), while no significantly different was found in CD206 and IL-10. In addition, Dex treatment down-regulated the expression of NR2B and reduced the frequency and amplitude of sEPSCs in I/R model mice (all p < 0.05), while Oxy had no significant effect on them. Tourniquet-induced I/R could impair the neurocognitive function of mice. Dex treatment could alleviate I/R-induced neurocognitive disorder by inhibiting abnormal synaptic transmission in hippocampal neurons. Both Dex and Oxy could alleviate the inflammatory response likely by inhibiting the polarization of microglia toward M1 phenotype via TLR4/NF-κB pathway. Future studies are needed to further examine the effects of Dex on neurocognitive disorder after tourniquet-induced I/R injury and investigate the exact mechanism.
Saliva diagnostics utilizing nanotechnology and molecular technologies to detect oral squamous cell carcinoma (OSCC) has become an attractive field of study. However, no specific methods have been established. To refine the diagnostic power of saliva peptide fingerprints for the early detection of OSCC, we screened the expression spectrum of salivary peptides in 40 T1 stage OSCC patients (and healthy controls) using MALDI-TOF-MS combined with magnetic beads. Fifty proteins showed significantly different expression levels in the OSCC samples (P<0.05). Potential biomarkers were also predicted. The novel diagnostic proteomic model with m/z peaks of 1285.6 Da and 1432.2 Da are of certain value for early diagnosis of OSCC. 相似文献
Trichloroethylene (TCE) degradation and the variations of bacteria composition and structure in the up-flow anaerobic sludge blanket (UASB) reactor were investigated by increasing the operating temperature from 20 to 40 °C. The influent was supplemented with 36.5 mg/L of TCE. There was a rise in the chemical oxygen demand (COD) removal efficiency from 20 to 35 °C and a decline when temperature enhanced to 40 °C. It reached maximum at 35 °C. In addition, TCE removal efficiency increased with temperature varying from 20 to 35 °C, and it dropped dramatically to 78.38 % at 40 °C, which presumably because the genus of Dehalobacter, a kind of bacteria with the ability to dechlorinate TCE to the corresponding chlorinated products, was not detected at 40 °C according to sequencing results. The Illumina MiSeq platform was adopted to explore the bacteria composition and structure in response to temperature shifts. The results indicated that temperature impacted greatly on the dominance and presence of specific populations at different taxonomic levels. Importantly, the class Dehalococcoidia was detected from 25 to 40 °C, in which there were many well-known Dehalococcoides sp. strains that were capable of complete dechlorination of TCE to ethene. It also suggested the potential function of the dominant genera (non-dechlorinating bacteria and dechlorinating bacteria) in the reactor. 相似文献
The major characteristics of pancreatic cancer are its excessive local invasion and early systemic dissemination. The glucose-regulated protein is over-expressed in many human cancers including pancreatic cancer and correlated with invasion and metastasis in many cancers. To investigate the effect of Grp78 on the invasion of pancreatic cancer, we used western blot and Transwell assay. We found Grp78 is expressed at lower levels in capan-2 and higher expressed in MiaPaCa-2 cells, and Grp78 expression levels were correlated with the invasion potentials of tumor cells. Then,we increased the expression of Grp78 in capan-2 cells and decreased the expression of Grp78 in MiaPaCa-2 cells. We found that over-expression of Grp78 caused significant increase in the expression of TIMP-1, TIMP-2, MMP-14, MMP-2, and MMP-9 in Capan-2 cells. Consistently, knockdown of Grp78 decreased the expression of them in MiaPaCa-2 cells. Gelatin zymography showed Grp78 over-expression stimulated the activities of MMP-2 and MMP-9, while GRP78 knockdown reduced the activities of MMP-2 and MMP-9. Cytoskeleton staining showed that knockdown of Grp78 caused a marked increase in cytoskeleton F-actin stress fibers in MiaPaCa-2 cells. Consistently, GRP78 knockdown hyperactivated RhoA and inhibited significantly Rac activity. Grp78 over-expression decreases the RhoA and stimulated Rac activity. We also found that Grp78 modulated FAK and JNK signaling pathways. Over-expression of GRP78 in Capan-2 activated FAK and JNK. Finally, we demonstrated that knockdown of FAK by shRNA in combination with blockade of JNK signaling pathway with SP600125 completely inhibited GRP78-induced cancer cell invasion. GRP78 is involved in the regulation of pancreatic cancer invasion. FAK and JNK are the key downstream effectors of GRP78. 相似文献