Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a gua...Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a guanine nucleotide exchange factor that is related to microglial activation.However,how Vav1 participates in the inflammato ry response after cerebral ischemia/reperfusion inj ury remains unclea r.In this study,we subjected rats to occlusion and repe rfusion of the middle cerebral artery and subjected the BV-2 mic roglia cell line to oxygen-glucose deprivatio n/reoxygenation to mimic cerebral ischemia/repe rfusion in vivo and in vitro,respectively.We found that Vav1 levels were increased in the brain tissue of rats subjected to occlusion and reperfusion of the middle cerebral arte ry and in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation.Silencing Vav1 reduced the cerebral infarct volume and brain water content,inhibited neuronal loss and apoptosis in the ischemic penumbra,and im p roved neurological function in rats subjected to occlusion and repe rfusion of the middle cerebral artery.Further analysis showed that Vav1 was almost exclusively localized to microglia and that Vav1 downregulation inhibited microglial activation and the NOD-like receptor pyrin 3(NLRP3) inflammasome in the ischemic penumbra,as well as the expression of inflammato ry facto rs.In addition,Vov1 knoc kdown decreased the inflammatory response exhibited by BV-2 cells after oxygen-glucose deprivation/reoxyge nation.Taken together,these findings show that silencing Vav1 attenuates inflammation and neuronal apoptosis in rats subjected to cerebral ischemia/repe rfusion through inhibiting the activation of mic roglia and NLRP3 inflammasome.展开更多
Objective:To study the correlation of Vav1 and cathepsin D (CTSD) expression with the clinical biological behaviors in endoscopic biopsy gastric cancer tissue.Methods: Patients who were diagnosed with gastric cancer b...Objective:To study the correlation of Vav1 and cathepsin D (CTSD) expression with the clinical biological behaviors in endoscopic biopsy gastric cancer tissue.Methods: Patients who were diagnosed with gastric cancer by gastroscopic biopsy in the 252 Hospital of PLA between April 2015 and December 2017 were selected, and the gastric cancer tissues and adjacent tissues from endoscopic biopsy were collected to determine the expression of Vav1, CTSD, invasion genes and proliferation genes.Results: Vav1, CTSD, HDAC5, Twist1, N-cadherin, MMP2, PTP1B, ATAD2, CyclinD1 and PCNA mRNA expression in gastric cancer tissues were significantly higher than those in adjacent tissues whereas BTG3, WTX, FAF1, Fas and Mxi1 mRNA expression were significantly lower than those in adjacent tissues;Vav1 and CTSD mRNA expression in gastric cancer tissues were positively correlated with HDAC5, Twist1, N-cadherin, MMP2, PTP1B, ATAD2, CyclinD1 and PCNA mRNA expression, and negatively correlated with BTG3, WTX, FAF1, Fas and Mxi1 mRNA expression.Conclusion:The high expression of Vav1 and CTSD in the endoscopic biopsy gastric cancer tissues is correlated with the invasion genes and proliferation genes that are related to the clinical biological behaviors of the tumor.展开更多
基金Natural Science Foundation of Liaoning Province (General Program),No.2017010825 (to JQ)。
文摘Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a guanine nucleotide exchange factor that is related to microglial activation.However,how Vav1 participates in the inflammato ry response after cerebral ischemia/reperfusion inj ury remains unclea r.In this study,we subjected rats to occlusion and repe rfusion of the middle cerebral artery and subjected the BV-2 mic roglia cell line to oxygen-glucose deprivatio n/reoxygenation to mimic cerebral ischemia/repe rfusion in vivo and in vitro,respectively.We found that Vav1 levels were increased in the brain tissue of rats subjected to occlusion and reperfusion of the middle cerebral arte ry and in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation.Silencing Vav1 reduced the cerebral infarct volume and brain water content,inhibited neuronal loss and apoptosis in the ischemic penumbra,and im p roved neurological function in rats subjected to occlusion and repe rfusion of the middle cerebral artery.Further analysis showed that Vav1 was almost exclusively localized to microglia and that Vav1 downregulation inhibited microglial activation and the NOD-like receptor pyrin 3(NLRP3) inflammasome in the ischemic penumbra,as well as the expression of inflammato ry facto rs.In addition,Vov1 knoc kdown decreased the inflammatory response exhibited by BV-2 cells after oxygen-glucose deprivation/reoxyge nation.Taken together,these findings show that silencing Vav1 attenuates inflammation and neuronal apoptosis in rats subjected to cerebral ischemia/repe rfusion through inhibiting the activation of mic roglia and NLRP3 inflammasome.
文摘Objective:To study the correlation of Vav1 and cathepsin D (CTSD) expression with the clinical biological behaviors in endoscopic biopsy gastric cancer tissue.Methods: Patients who were diagnosed with gastric cancer by gastroscopic biopsy in the 252 Hospital of PLA between April 2015 and December 2017 were selected, and the gastric cancer tissues and adjacent tissues from endoscopic biopsy were collected to determine the expression of Vav1, CTSD, invasion genes and proliferation genes.Results: Vav1, CTSD, HDAC5, Twist1, N-cadherin, MMP2, PTP1B, ATAD2, CyclinD1 and PCNA mRNA expression in gastric cancer tissues were significantly higher than those in adjacent tissues whereas BTG3, WTX, FAF1, Fas and Mxi1 mRNA expression were significantly lower than those in adjacent tissues;Vav1 and CTSD mRNA expression in gastric cancer tissues were positively correlated with HDAC5, Twist1, N-cadherin, MMP2, PTP1B, ATAD2, CyclinD1 and PCNA mRNA expression, and negatively correlated with BTG3, WTX, FAF1, Fas and Mxi1 mRNA expression.Conclusion:The high expression of Vav1 and CTSD in the endoscopic biopsy gastric cancer tissues is correlated with the invasion genes and proliferation genes that are related to the clinical biological behaviors of the tumor.
