脉冲星在天体演化、物理学、计时、深空自主导航、引力波探测等领域均有重要的学术和应用价值,脉冲星搜寻及其应用也成为了当前天文界热点研究之一。为了更好地探究脉冲星搜寻及其应用领域的研究现状和未来发展趋势,在Web of Science(W...脉冲星在天体演化、物理学、计时、深空自主导航、引力波探测等领域均有重要的学术和应用价值,脉冲星搜寻及其应用也成为了当前天文界热点研究之一。为了更好地探究脉冲星搜寻及其应用领域的研究现状和未来发展趋势,在Web of Science(WOS)数据库筛选出有关脉冲星搜寻及应用的964篇文献,在阅读核心文献的基础上,采用数据分析和可视化方法进行深入探讨。结果表明,脉冲星搜寻及应用领域的研究经历了初始探索阶段和稳健发展阶段,目前进入蓬勃增长阶段。该领域各国之间密切合作,形成了三大主要的研究群体。脉冲星搜寻及其应用研究在未来将产生如直接探测引力波、深空自主导航等重要科研价值和实际应用结果,将进一步丰富和多元化脉冲星的研究领域。展开更多
OBJECTIVE To investigate berberine(BBR)attenuates arthritis in adjuvant-induced arthritic(AA)rats associated with regulating the energy metabolism and correcting the polarization of macrophages through activation of A...OBJECTIVE To investigate berberine(BBR)attenuates arthritis in adjuvant-induced arthritic(AA)rats associated with regulating the energy metabolism and correcting the polarization of macrophages through activation of AMP-activated protein kinase(AMPK)and inhibition of hypoxia inducible factor 1α(HIF-1α).METHODS AA rats were treated with BBR(40,80,or 160 mg·kg-1)from days 15 to 29 after immunization.The histopathology of ankle joint was examined through hematoxylin-eosin(HE)staining.The concentrations of tumour necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,IL-2,IL-17A,interferon-gamma(IFN-γ),monocyte chemotactic protein 1(MCP-1),IL-4,IL-10,transforming growth factor-β1(TGF-β1),ATP,and lactic acid were measured by using ELISA kits.The percentage of M1 and M2 macro⁃phage cells in joint tissues were evaluated by immune-fluorescence.The expressions of p-AMPK and HIF-1αin joint of AA rats were determined according to immunohistochemistry analysis.The migration of macrophage was detected by Transwell assays.The expression of inducible nitric oxide synthase(iNOS),Arginase-1(Arg1),p-AMPK,AMPK and HIF-1αwere examined by Western blotting.The labeled macrophages were observed with laser confocal microscopy.RESULTS BBR relieved signs and symptoms of AA rats and reversed pathological changes.BBR treatment group exhibited decreases in pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-2,IL-17A,IFN-γ,and MCP-1)coupled with increases anti-inflammatory cytokines(IL-4,IL-10,TGF-β1)in the serum.The number of M1 macrophage was reduced,while the number of M2 macrophage was increased in BBR group joint tissues.Moreover,BBR showed marked up-regu⁃lation the expression of p-AMPK and down-regulation the expression of HIF-1αin joint of AA rats.Next in vitro study,we found BBR up-regulated the expression of p-AMPK,Arg1(M2 marker)and down-regulated the expression of HIF-1α,iNOS(M1 marker)induced by LPS in peritoneal macrophages from normal SD rat.Furthermore,BBR treatment inhibited the migration of macrophages stimulated by LPS.The level of ATP was elevated and lactic acid was reduced in LPSinduced macrophages after treated by BBR.However,Compound C significantly attenuated the effects of BBR on acti⁃vated macrophages.CONCLUSION BBR alleviates inflammation by regulating energy metabolism and correcting the polarization of macrophage through AMPK-HIF-1αpathway.BBR might have great therapeutic value for RA.展开更多
文摘脉冲星在天体演化、物理学、计时、深空自主导航、引力波探测等领域均有重要的学术和应用价值,脉冲星搜寻及其应用也成为了当前天文界热点研究之一。为了更好地探究脉冲星搜寻及其应用领域的研究现状和未来发展趋势,在Web of Science(WOS)数据库筛选出有关脉冲星搜寻及应用的964篇文献,在阅读核心文献的基础上,采用数据分析和可视化方法进行深入探讨。结果表明,脉冲星搜寻及应用领域的研究经历了初始探索阶段和稳健发展阶段,目前进入蓬勃增长阶段。该领域各国之间密切合作,形成了三大主要的研究群体。脉冲星搜寻及其应用研究在未来将产生如直接探测引力波、深空自主导航等重要科研价值和实际应用结果,将进一步丰富和多元化脉冲星的研究领域。
文摘目的:探讨二甲双胍治疗类风湿性关节炎(rheumatoidrthritis arthritis,RA)骨破坏的作用及机制。方法:采用Freund完全佐剂诱导佐剂性关节炎(adjuvant arthritis,AA)大鼠模型。全身评分评价不同剂量二甲双胍对AA大鼠炎症的作用;对各组大鼠踝关节和足部通过X射线成像进行检查;ELISA法对大鼠外周血中钙离子、磷离子、骨保护素(OPG)、核因子κB受体活化因子配体(RANKL)等指标进行测定;免疫组织化学法测定大鼠膝关节腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)蛋白表达。探讨二甲双胍对AA大鼠骨破坏的影响及机制。结果:二甲双胍可以改善AA大鼠的全身炎症反应,减轻足爪部肿胀,尤其是高剂量效果更明显。二甲双胍各剂量组均可明显改善AA大鼠的局部骨密度降低和骨缺损;二甲双胍高剂量组血清钙、磷离子水平升高;不同剂量的二甲双胍均可以提高血清OPG,降低RANKL的水平;与模型组相比,二甲双胍可增加AMPK蛋白表达,降低IL-6、TNF-α蛋白表达,以上差异均有统计学意义(P<0.05~P<0.01)。结论:二甲双胍可对RA骨破坏起到保护作用;作用机制可能与其抗炎、调节血清骨代谢指标及激活AMPK信号通路影响OPG-RANKL-RANK系统相关。
基金National Natural Science Foundation of China(81703529)
文摘OBJECTIVE To investigate berberine(BBR)attenuates arthritis in adjuvant-induced arthritic(AA)rats associated with regulating the energy metabolism and correcting the polarization of macrophages through activation of AMP-activated protein kinase(AMPK)and inhibition of hypoxia inducible factor 1α(HIF-1α).METHODS AA rats were treated with BBR(40,80,or 160 mg·kg-1)from days 15 to 29 after immunization.The histopathology of ankle joint was examined through hematoxylin-eosin(HE)staining.The concentrations of tumour necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,IL-2,IL-17A,interferon-gamma(IFN-γ),monocyte chemotactic protein 1(MCP-1),IL-4,IL-10,transforming growth factor-β1(TGF-β1),ATP,and lactic acid were measured by using ELISA kits.The percentage of M1 and M2 macro⁃phage cells in joint tissues were evaluated by immune-fluorescence.The expressions of p-AMPK and HIF-1αin joint of AA rats were determined according to immunohistochemistry analysis.The migration of macrophage was detected by Transwell assays.The expression of inducible nitric oxide synthase(iNOS),Arginase-1(Arg1),p-AMPK,AMPK and HIF-1αwere examined by Western blotting.The labeled macrophages were observed with laser confocal microscopy.RESULTS BBR relieved signs and symptoms of AA rats and reversed pathological changes.BBR treatment group exhibited decreases in pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-2,IL-17A,IFN-γ,and MCP-1)coupled with increases anti-inflammatory cytokines(IL-4,IL-10,TGF-β1)in the serum.The number of M1 macrophage was reduced,while the number of M2 macrophage was increased in BBR group joint tissues.Moreover,BBR showed marked up-regu⁃lation the expression of p-AMPK and down-regulation the expression of HIF-1αin joint of AA rats.Next in vitro study,we found BBR up-regulated the expression of p-AMPK,Arg1(M2 marker)and down-regulated the expression of HIF-1α,iNOS(M1 marker)induced by LPS in peritoneal macrophages from normal SD rat.Furthermore,BBR treatment inhibited the migration of macrophages stimulated by LPS.The level of ATP was elevated and lactic acid was reduced in LPSinduced macrophages after treated by BBR.However,Compound C significantly attenuated the effects of BBR on acti⁃vated macrophages.CONCLUSION BBR alleviates inflammation by regulating energy metabolism and correcting the polarization of macrophage through AMPK-HIF-1αpathway.BBR might have great therapeutic value for RA.
