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
目的探讨信号转导与转录激活因子5A(signal transducer and activator of transcription 5A,STAT5A)在弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中的表达及临床意义。方法采用免疫组化法检测106例DLBCL中STAT5及磷酸化ST...目的探讨信号转导与转录激活因子5A(signal transducer and activator of transcription 5A,STAT5A)在弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中的表达及临床意义。方法采用免疫组化法检测106例DLBCL中STAT5及磷酸化STAT5A^(Tyr694)(pSTAT5A^(Y694))的表达,分析STAT5核表达水平及pSTAT5A^(Y694)表达水平与DLBCL临床病理特征及预后的相关性。结果STAT5核表达与骨髓浸润(P=0.004)、治疗反应(P=0.001)相关,其在有骨髓浸润、疾病进展/稳定患者中的表达高于无骨髓浸润、部分缓解(partial response,PR)/完全缓解(complete response,CR)患者。pSTAT5A^(Y694)表达水平与Ki-67增殖指数(P=0.022)、治疗反应(P=0.003)相关,其在Ki-67增殖指数≥75%、疾病进展/稳定患者中的表达高于Ki-67增殖指数<75%、PR/CR患者。STAT5核表达以及pSTAT5A^(Y694)表达水平与其它临床病理特征均无关(P均>0.05)。Kaplan-Meier生存分析显示:STAT5核阳性DLBCL患者的总生存期(overall survival,OS)低于阴性患者(P=0.0117);且pSTAT5A^(Y694)阳性患者的OS低于阴性患者(P=0.0102)。单因素和多因素Cox回归分析显示:STAT5核表达水平(P=0.243)、pSTAT5A^(Y694)表达水平(P=0.093)是影响OS的相关因素,但不是预后的独立影响因素。结论STAT5核表达以及pSTAT5A^(Y694)表达与DLBCL患者的治疗反应相关。STAT5核阳性、pSTAT5A^(Y694)阳性DLBCL患者的OS比阴性患者缩短;STAT5核表达水平、pSTAT5A^(Y694)表达水平是影响OS的相关因素,但不是预后的独立影响因素。展开更多
【目的】探讨JAK-STAT通路中瘦素(Leptin,LEP)和信号转导子和转录激活子5a(signal transducers and activators of transcription,STAT5a)基因在崂山奶山羊群体中的遗传变异、交互作用及与生产性状的关联性。【方法】以174只崂山奶山羊...【目的】探讨JAK-STAT通路中瘦素(Leptin,LEP)和信号转导子和转录激活子5a(signal transducers and activators of transcription,STAT5a)基因在崂山奶山羊群体中的遗传变异、交互作用及与生产性状的关联性。【方法】以174只崂山奶山羊泌乳母羊为实验群体,其中89只来自种羊场,有完整的产奶量记录;85只来自育种户。利用DNA混池测序和候选基因直接测序技术检测LEP基因外显子2、外显子3和STAT5a基因外显子10、外显子16在该群体中的多态性,并采用最小二乘法分析了多态性位点与乳成分、校正产奶量、生长性状的关联效应。【结果】在所研究的群体中,LEP基因外显子2、3和STAT5a基因外显子10、16上均不存在多态性。LEP基因内含子2上存在一个A→G的单核苷酸替换,对于泌乳和生长性状而言,模型和场别效应均达到显著水平,该位点对育种场中校正产奶量和尻宽、育种户中体高有显著(P<0.05)或极显著(P<0.01)影响;STAT5a基因内含子9上存在A→G的单核苷酸替换和T→C的单核苷酸替换,这两个突变为连锁突变,对泌乳性状没有显著影响(P>0.05),对整个群体体长和胸围有显著(P<0.05)影响,对育种户胸围有极显著(P<0.01)影响。【结论】在崂山奶山羊中发现候选基因LEP和STAT5a存在多态性,相互之间没有交互作用,L393位点对育种场中校正产奶量和尻宽、育种户中体高有显著效应,S163/S206位点对整个群体的体重、体长和胸围,对育种户胸围有显著效应。因此,LEP和STAT5a基因可以作为崂山奶山羊产奶量及部分生长性状的遗传标记。展开更多
【目的】探究绵羊信号传感器和转录激活器5A(signal transducer and activator of transcription 5A,STAT5a)基因第10内含子多态位点及其与泌乳性状的相关性,为湖羊分子标记选育提供参考依据。【方法】采集71只湖羊母羊血液,通过PCR扩增...【目的】探究绵羊信号传感器和转录激活器5A(signal transducer and activator of transcription 5A,STAT5a)基因第10内含子多态位点及其与泌乳性状的相关性,为湖羊分子标记选育提供参考依据。【方法】采集71只湖羊母羊血液,通过PCR扩增和Sanger测序法检测湖羊STAT5a基因第10内含子单核苷酸多态性(SNP)位点,并利用SAS 9.4软件分析STAT5a基因SNP位点多态性与7~56 d湖羊产奶量、乳脂率、乳蛋白率、体细胞数等性状的相关性。【结果】湖羊STAT5a基因第10内含子检测出1个SNP位点:g.41838147 A>G,在该位点发现AA、AG和GG 3种基因型。卡方适合性检验表明,g.41838147 A>G突变位点偏离Hardy-Weinberg平衡状态(P<0.05)。多态信息含量(PIC)计算显示,g.41838147 A>G位点为中度多态(0.25G位点的GG基因型个体7~56 d总产奶量极显著或显著高于AA、AG基因型(P<0.01;P<0.05),平均乳糖率显著高于AA基因型(P<0.05);AG、GG基因型个体的平均体细胞数显著低于AA基因型(P<0.05)。【结论】STAT5a基因第10内含子存在1个多态性位点,与湖羊总产奶量、平均乳糖率和平均体细胞数均有显著关联性。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.
文摘目的探讨信号转导与转录激活因子5A(signal transducer and activator of transcription 5A,STAT5A)在弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中的表达及临床意义。方法采用免疫组化法检测106例DLBCL中STAT5及磷酸化STAT5A^(Tyr694)(pSTAT5A^(Y694))的表达,分析STAT5核表达水平及pSTAT5A^(Y694)表达水平与DLBCL临床病理特征及预后的相关性。结果STAT5核表达与骨髓浸润(P=0.004)、治疗反应(P=0.001)相关,其在有骨髓浸润、疾病进展/稳定患者中的表达高于无骨髓浸润、部分缓解(partial response,PR)/完全缓解(complete response,CR)患者。pSTAT5A^(Y694)表达水平与Ki-67增殖指数(P=0.022)、治疗反应(P=0.003)相关,其在Ki-67增殖指数≥75%、疾病进展/稳定患者中的表达高于Ki-67增殖指数<75%、PR/CR患者。STAT5核表达以及pSTAT5A^(Y694)表达水平与其它临床病理特征均无关(P均>0.05)。Kaplan-Meier生存分析显示:STAT5核阳性DLBCL患者的总生存期(overall survival,OS)低于阴性患者(P=0.0117);且pSTAT5A^(Y694)阳性患者的OS低于阴性患者(P=0.0102)。单因素和多因素Cox回归分析显示:STAT5核表达水平(P=0.243)、pSTAT5A^(Y694)表达水平(P=0.093)是影响OS的相关因素,但不是预后的独立影响因素。结论STAT5核表达以及pSTAT5A^(Y694)表达与DLBCL患者的治疗反应相关。STAT5核阳性、pSTAT5A^(Y694)阳性DLBCL患者的OS比阴性患者缩短;STAT5核表达水平、pSTAT5A^(Y694)表达水平是影响OS的相关因素,但不是预后的独立影响因素。
文摘【目的】探讨JAK-STAT通路中瘦素(Leptin,LEP)和信号转导子和转录激活子5a(signal transducers and activators of transcription,STAT5a)基因在崂山奶山羊群体中的遗传变异、交互作用及与生产性状的关联性。【方法】以174只崂山奶山羊泌乳母羊为实验群体,其中89只来自种羊场,有完整的产奶量记录;85只来自育种户。利用DNA混池测序和候选基因直接测序技术检测LEP基因外显子2、外显子3和STAT5a基因外显子10、外显子16在该群体中的多态性,并采用最小二乘法分析了多态性位点与乳成分、校正产奶量、生长性状的关联效应。【结果】在所研究的群体中,LEP基因外显子2、3和STAT5a基因外显子10、16上均不存在多态性。LEP基因内含子2上存在一个A→G的单核苷酸替换,对于泌乳和生长性状而言,模型和场别效应均达到显著水平,该位点对育种场中校正产奶量和尻宽、育种户中体高有显著(P<0.05)或极显著(P<0.01)影响;STAT5a基因内含子9上存在A→G的单核苷酸替换和T→C的单核苷酸替换,这两个突变为连锁突变,对泌乳性状没有显著影响(P>0.05),对整个群体体长和胸围有显著(P<0.05)影响,对育种户胸围有极显著(P<0.01)影响。【结论】在崂山奶山羊中发现候选基因LEP和STAT5a存在多态性,相互之间没有交互作用,L393位点对育种场中校正产奶量和尻宽、育种户中体高有显著效应,S163/S206位点对整个群体的体重、体长和胸围,对育种户胸围有显著效应。因此,LEP和STAT5a基因可以作为崂山奶山羊产奶量及部分生长性状的遗传标记。
