Neuroinflammation plays an important role in the occurrence and development of neurological diseases.In addition to microglia,the role of astrocytes in neuroinflammation has gradually attracted attention.Photobiomodul...Neuroinflammation plays an important role in the occurrence and development of neurological diseases.In addition to microglia,the role of astrocytes in neuroinflammation has gradually attracted attention.Photobiomodulation(PBM),as a non-invasive treatment,has been shown potential to alleviate inflammation of microglia or astrocytes.In this study,the spatiotemporal regulation and molecular mechanism of PBM on astrocytes were deeply explored by analyzing the effects and genomics at different time points.The results showed that PBM significantly attenuated the upregulation of inflammatory factors and mitochondrial dysfunction in astrocytes under LPS stimulation for 4 h and 24 h.RNA-seq analysis showed that the JAK-STAT pathway played an important role in the early stage of both LPS-induced astrocytic neuroin-flammation and PBM-alleviated astrocytic neuroinflammation.Under PBM treatment,Stat5a translocation to the nucleus and upregulated Socs3 expression were observed in LPS-treated astrocytes,which may inhibit the overactivation of the JAK-STAT inflammatory signaling pathway and thus alleviate astrocyte inflammation.Taken together,this study provides new insight into the molecular mechanism of the potential application of PBM in the treatment of neuroinflammation.展开更多
Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effec...Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects,and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models.Here,we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta(CaMKKβ)/adenosine 5′-monophosphate-activated protein kinase(AMPK)/suppressor of cytokine signaling-3(SOCS3)signaling in microglia.Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation.Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia,which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain,thereby suppressing neuroinflammation.The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia.The results suggested that focal repetitive trans-spinal magnetic stimulation inhibits spinal neuroinflammation and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia.This mechanism provides an effective noninvasive treatment for neuropathic pain caused by peripheral nerve injury.展开更多
目的:观察电针对神经病理性疼痛大鼠痛行为学及脊髓细胞因子信号转导抑制蛋白3(SOCS3)表达的影响。方法:SD大鼠随机分为正常组、假手术组、模型组、电针组、非电针组,每组10只。采用坐骨神经结扎压迫建立慢性限制性损伤(CCI)神经痛模型...目的:观察电针对神经病理性疼痛大鼠痛行为学及脊髓细胞因子信号转导抑制蛋白3(SOCS3)表达的影响。方法:SD大鼠随机分为正常组、假手术组、模型组、电针组、非电针组,每组10只。采用坐骨神经结扎压迫建立慢性限制性损伤(CCI)神经痛模型,电针组选取双侧"阳陵泉"、"环跳"穴进行电针治疗,观察大鼠痛行为学和脊髓SOCS3、IL-6基因表达的变化,检测脊髓SOCS3神经细胞定位情况。结果:与模型组相比,电针可显著提高CCI大鼠机械痛及热痛阈值(P<0.01);与正常组相比,模型组大鼠脊髓SOCS3、IL-6 m RNA表达显著上调(P<0.01),而电针可显著降低IL-6m RNA表达,并进一步上调脊髓SOCS3表达水平(P<0.01)。在CCI大鼠中,SOCS3主要表达于脊髓星形胶质细胞和小胶质细胞中。结论:电针可能通过下调IL-6基因表达,并上调SOCS3表达,减轻神经痛大鼠痛敏反应。展开更多
目的观察鼻息肉患者磷酸化信号转导与转录激活因子3(phospho-signal transducers and activators of transcription,p-STAT3)、SOCS3(suppressor of cytokine signaling,SOCS3)及Th17相关因子的水平,初步探讨STAT3及SOCS3对鼻息肉患者T...目的观察鼻息肉患者磷酸化信号转导与转录激活因子3(phospho-signal transducers and activators of transcription,p-STAT3)、SOCS3(suppressor of cytokine signaling,SOCS3)及Th17相关因子的水平,初步探讨STAT3及SOCS3对鼻息肉患者Th17细胞功能的作用。方法选取40例鼻息肉患者标本及15例对照组标本,采用免疫组化和蛋白免疫印迹法检测p-STAT3及SOCS3在鼻息肉组织中的分布及表达,运用ELISA法检测IL-6和IL-17A的表达情况,采用RT-PCR检测RORγt的表达水平,并对数据进行统计学分析。结果鼻息肉组的p-STAT3、IL-6、IL-17A以及RORγt表达明显高于对照组(P<0.01),SOCS3在鼻息肉组中的表达则低于对照组(P<0.01)。相关性分析显示p-STAT3、RORγt及IL-17A与SOCS3呈负相关(p-STAT3/SOCS3:r=-0.545,P<0.01;RORγt/SOCS3:r=-0.627,P<0.05;IL-17A/SOCS3:r=-0.631,P<0.01),而p-STAT3与RORγt、IL-6、IL-17A呈正相关(p-STAT3/RORγt:r=0.594,P<0.001;p-STAT3/IL-6:r=0.632,P<0.001;p-STAT3/IL-17A:r=0.647,P<0.01)。结论 STAT3异常活化,以及SOCS3低表达所致抑制作用缺失可能是造成鼻息肉中Th17细胞过度活化的重要原因。展开更多
基金funded in part by the STI2030-Major Projects(2022ZD0212200)Hainan Province Key Area R&D Program(KJRC2023C30)+1 种基金Project of Collaborative Innovation Center of One Health(XTCX2022JKB02)Sanya Yazhou Bay Science and Technology City(SKJC-JYRC-2024-38).
文摘Neuroinflammation plays an important role in the occurrence and development of neurological diseases.In addition to microglia,the role of astrocytes in neuroinflammation has gradually attracted attention.Photobiomodulation(PBM),as a non-invasive treatment,has been shown potential to alleviate inflammation of microglia or astrocytes.In this study,the spatiotemporal regulation and molecular mechanism of PBM on astrocytes were deeply explored by analyzing the effects and genomics at different time points.The results showed that PBM significantly attenuated the upregulation of inflammatory factors and mitochondrial dysfunction in astrocytes under LPS stimulation for 4 h and 24 h.RNA-seq analysis showed that the JAK-STAT pathway played an important role in the early stage of both LPS-induced astrocytic neuroin-flammation and PBM-alleviated astrocytic neuroinflammation.Under PBM treatment,Stat5a translocation to the nucleus and upregulated Socs3 expression were observed in LPS-treated astrocytes,which may inhibit the overactivation of the JAK-STAT inflammatory signaling pathway and thus alleviate astrocyte inflammation.Taken together,this study provides new insight into the molecular mechanism of the potential application of PBM in the treatment of neuroinflammation.
基金National Natural Science Foundation of China,Nos.82302877(to QW),82172541(to TW)the Natural Science Foundation of Hunan Province,No.2023JJ30549(to QW)Clinical Medical Technology Innovation Guidance Project of Hunan Provincial Science and Technology Department,No.2021SK51815(to QW).
文摘Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects,and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models.Here,we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta(CaMKKβ)/adenosine 5′-monophosphate-activated protein kinase(AMPK)/suppressor of cytokine signaling-3(SOCS3)signaling in microglia.Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation.Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia,which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain,thereby suppressing neuroinflammation.The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia.The results suggested that focal repetitive trans-spinal magnetic stimulation inhibits spinal neuroinflammation and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia.This mechanism provides an effective noninvasive treatment for neuropathic pain caused by peripheral nerve injury.
文摘目的:观察电针对神经病理性疼痛大鼠痛行为学及脊髓细胞因子信号转导抑制蛋白3(SOCS3)表达的影响。方法:SD大鼠随机分为正常组、假手术组、模型组、电针组、非电针组,每组10只。采用坐骨神经结扎压迫建立慢性限制性损伤(CCI)神经痛模型,电针组选取双侧"阳陵泉"、"环跳"穴进行电针治疗,观察大鼠痛行为学和脊髓SOCS3、IL-6基因表达的变化,检测脊髓SOCS3神经细胞定位情况。结果:与模型组相比,电针可显著提高CCI大鼠机械痛及热痛阈值(P<0.01);与正常组相比,模型组大鼠脊髓SOCS3、IL-6 m RNA表达显著上调(P<0.01),而电针可显著降低IL-6m RNA表达,并进一步上调脊髓SOCS3表达水平(P<0.01)。在CCI大鼠中,SOCS3主要表达于脊髓星形胶质细胞和小胶质细胞中。结论:电针可能通过下调IL-6基因表达,并上调SOCS3表达,减轻神经痛大鼠痛敏反应。
文摘目的观察鼻息肉患者磷酸化信号转导与转录激活因子3(phospho-signal transducers and activators of transcription,p-STAT3)、SOCS3(suppressor of cytokine signaling,SOCS3)及Th17相关因子的水平,初步探讨STAT3及SOCS3对鼻息肉患者Th17细胞功能的作用。方法选取40例鼻息肉患者标本及15例对照组标本,采用免疫组化和蛋白免疫印迹法检测p-STAT3及SOCS3在鼻息肉组织中的分布及表达,运用ELISA法检测IL-6和IL-17A的表达情况,采用RT-PCR检测RORγt的表达水平,并对数据进行统计学分析。结果鼻息肉组的p-STAT3、IL-6、IL-17A以及RORγt表达明显高于对照组(P<0.01),SOCS3在鼻息肉组中的表达则低于对照组(P<0.01)。相关性分析显示p-STAT3、RORγt及IL-17A与SOCS3呈负相关(p-STAT3/SOCS3:r=-0.545,P<0.01;RORγt/SOCS3:r=-0.627,P<0.05;IL-17A/SOCS3:r=-0.631,P<0.01),而p-STAT3与RORγt、IL-6、IL-17A呈正相关(p-STAT3/RORγt:r=0.594,P<0.001;p-STAT3/IL-6:r=0.632,P<0.001;p-STAT3/IL-17A:r=0.647,P<0.01)。结论 STAT3异常活化,以及SOCS3低表达所致抑制作用缺失可能是造成鼻息肉中Th17细胞过度活化的重要原因。
