Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in ...Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.展开更多
Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that ...Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.展开更多
基金supported by the Youth Development Project of Air Force Military Medical University,No.21 QNPY072Key Project of Shaanxi Provincial Natural Science Basic Research Program,No.2023-JC-ZD-48(both to FF)。
文摘Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.
基金National Key R&D Program of China,Nos.2019YFA0110300 (to LZ),2021YFA1201400 (to LZ)Natural Science Foundation of Shanghai,No.21ZR1468600 (to LZ)Open Fund of the Key Laboratory of Cellular Physiology (Shanxi Medical University),Ministry of Education,No.KLMEC/SXMU-201910 (to XJ)。
文摘Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.
文摘目的 探讨超声造影参数联合血清成纤维细胞生长因子-23(fibroblast growth factor-23,FGF23)和成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)在诊断乳腺癌的临床应用价值。方法 选择2020年8月~2022年6月在新疆维吾尔自治区人民医院就诊的87例乳腺癌患者作为观察对象(恶性组),选取同期90例乳腺良性病变患者作为良性组,分析两组观察对象超声造影参数,酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清FGF23和FGFR1表达水平,Pearson法分析乳腺癌患者血清FGF23和FGFR1水平与超声造影参数的相关性,ROC曲线分析超声造影参数、血清FGF23和FGFR1对乳腺癌的诊断价值。结果 与良性组比较,恶性组的超声造影峰值强度(peak intensity,PI)(15.36±3.47 dB vs 12.54±2.83 dB)、曲线下面积(area under curve,AUC)(382.69±90.51 dB/s vs 262.95±75.34 dB/s)及血清FGF23(119.28±26.41 pg/ml vs 86.41±20.35 pg/ml),FGFR1(11.36±3.42 ng/mL vs 7.24±2.26 ng/mL)水平升高,达峰时间(time to peak,TTP)(18.46±4.31 s vs 24.23±5.25 s)降低,差异均有统计学意义(t=5.934~9.579,均P=0.000)。相关性分析显示,乳腺癌患者血清FGF23水平与PI,AUC呈正相关(r=0.493,0.561,均P=0.000),与TTP呈负相关(r=-0.572,P=0.000);血清FGFR1水平与PI,AUC呈正相关(r=0.603,0.491,均P=0.000),与TTP呈负相关(r=-0.545,P=0.000)。超声造影参数联合血清FGF23和FGFR1诊断乳腺癌的曲线下面积为0.971,联合诊断效能明显高于单独诊断,差异均有统计学意义(Z=6.478,5.558,4.839,4.780,4.943,均P <0.05)。结论 超声造影参数联合血清FGF23和FGFR1对乳腺癌具有较高诊断价值,可为乳腺癌的临床诊治提供参考。
