Objective To investigate the effects of calprotectin(S100A8/A9)on the biological activity of acute myeloid leukemia(AML)cells harboring a DNA methyltransferase 3A(DNMT3A)mutation and to explore the underlying molecula...Objective To investigate the effects of calprotectin(S100A8/A9)on the biological activity of acute myeloid leukemia(AML)cells harboring a DNA methyltransferase 3A(DNMT3A)mutation and to explore the underlying molecular mechanisms involved.Methods AML monoclonal cell lines harboring the DNMT3A^(R882H) mutation were generated via lentiviral transduction and limiting dilution.RNA sequencing was used for differential gene expression analysis,followed by bioinformatic pathway enrichment and gene correlation analyses.The biological effects of paquinimod,a selective S100A8/A9 inhibitor,on DNMT3A^(R882H) AML cells were assessed via Cell Counting Kit(CCK-8)proliferation assays,Annexin V/PI staining,cell cycle analysis,cell adhesion assays,and transwell migration assays.Results Differential gene expression analysis revealed 442 upregulated and 535 downregulated genes in DNMT3A-mutated(DNMT3A^(mut))cells compared with those in DNMT3A wild-type(DNMT3A^(wt))cells,with the S100A8/A9 complex recurrently enriched in Reactome pathway analysis.Compared with healthy controls,patients with AML presented increased expression of S100A8 and S100A9 and increased expression of DNMT3A^(mut) cells relative to DNMT3A^(wt) cells,which was correlated with poor prognosis in patients with AML.There were no notable differences in proliferation among the DNMT3A^(mut),DNMT3A^(wt),and empty vector cells under normal or starvation conditions.However,paquinimod treatment notably inhibited the proliferation,migration,and adhesion of DNMT3A^(mut) AML cells in a dose-dependent manner,causing G0/G1 cell cycle arrest,whereas no significant effects on apoptosis were observed.Paquinimod also downregulated key adhesion molecules,including intercellular adhesion molecule 1(ICAM-1),vascular cell adhesion molecule 1(VCAM-1),monocyte chemoattractant protein-1(MCP-1),and matrix metalloproteinase-2(MMP-2).Additionally,S100A8 and S100A9 expression was upregulated in a dose-dependent manner in response to cytarabine treatment.Conclusion Elevated S100A8/A9 expression contributes to the abnormal proliferation,migration,adhesion,and chemoresistance of DNMT3A^(mut) AML cells.Targeting S100A8/A9 alone or in combination with other treatments represents a promising therapeutic strategy for DNMT3A^(mut) AML.展开更多
目的:观察蒲公英多糖(dandelion polysaccharide,DP)对大鼠多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)肺、小肠组织炎症反应及S100钙结合蛋白A8/A9(S100 calcium-binding protein A8/A9,S100A8/A9)表达的影响。方...目的:观察蒲公英多糖(dandelion polysaccharide,DP)对大鼠多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)肺、小肠组织炎症反应及S100钙结合蛋白A8/A9(S100 calcium-binding protein A8/A9,S100A8/A9)表达的影响。方法:应用失血性休克及腹腔注射脂多糖“二次打击”的方法,构建大鼠MODS模型,分为假手术组、模型组、DP低剂量组、DP高剂量组。观察各组大鼠肺和小肠脏器系数及湿/干重比值;苏木精-伊红(hematoxylin-eosinstaining,HE)染色观察肺和小肠组织病理形态学改变;免疫组织化学染色观察肺和小肠组织白细胞介素(interleukin,IL)1β、IL-6、IL-10的表达;蛋白质免疫印迹法(Western blot)检测肺和小肠组织S100A8/A9蛋白表达变化。结果:与假手术组相比,模型组大鼠肺脏系数(5.849±0.824)、湿/干重比值(6.556±0.631)和小肠湿/干重比值(6.356±0.535)、湿重/长度比值(73.950±5.569)均上升。HE染色显示肺泡腔及肺间质可见大量炎细胞浸润,肺泡壁增厚;小肠绒毛崩解碎裂,可见炎细胞浸润及节段性集合淋巴滤泡增生。S100A8/A9主要表达于中性粒细胞和巨噬细胞,大鼠肺和小肠组织S100A8/A9、IL-1β、IL-6表达上调,IL-10表达下调。给予高剂量DP治疗后,大鼠肺脏系数(4.297±0.462)、湿/干重比值(5.313±0.495)和小肠湿/干重比值(5.398±0.388)、湿重/长度比值(59.417±2.891)均下降。肺和小肠组织病理损伤减轻,肺和小肠组织S100A8/A9、IL-1β、IL-6表达下调,IL-10表达上调。结论:DP可能通过抑制S100A8/A9的表达,减轻大鼠MODS肺和小肠组织损伤的炎症反应。展开更多
目的:探究血清细胞因子信号传导抑制蛋白1(suppressor of cytokine signaling 1,SOCS1)、S100钙结合蛋白A8(S100 calcium binding protein A8,S100A8)对肾结石术后尿路感染的诊断价值。方法:选取2023年4月—2024年4月于南京中医药大学...目的:探究血清细胞因子信号传导抑制蛋白1(suppressor of cytokine signaling 1,SOCS1)、S100钙结合蛋白A8(S100 calcium binding protein A8,S100A8)对肾结石术后尿路感染的诊断价值。方法:选取2023年4月—2024年4月于南京中医药大学张家港附属医院行输尿管软镜钬激光碎石术后尿路感染的134例肾结石患者为研究对象(尿路感染组),选取本院同期134例行输尿管软镜钬激光碎石术后尿路未感染的肾结石患者为无尿路感染组。采用ELISA法测定血清中SOCS1、S100A8水平。肾结石患者术后尿路感染的影响因素采用logistic回归分析;血清SOCS1、S100A8对肾结石术后尿路感染的诊断价值基于受试者工作特征(receiver operating characteristic,ROC)曲线分析。结果:2组肾结石患者在手术时间、双J管长度、双J管留置时间和结石残留上比较差异有统计学意义(P<0.05);尿路感染组血清SOCS1水平低于无尿路感染组,S100A8水平高于无尿路感染组(P<0.05);多因素logistic回归显示,血清S100A8手术时间大于1 h、双J管长度大于26 cm、双J管留置时间2周以上、结石残留是肾结石术后尿路感染的危险因素,血清SOCS1是肾结石术后尿路感染的保护因素(P<0.05);ROC曲线显示,血清SOCS1、S100A8及二者联合诊断肾结石术后尿路感染的曲线下面积(area under the curve,AUC)分别为0.759、0.816、0.915,两者联合诊断肾结石术后尿路感染的AUC显著高于SOCS1、S100A8单独诊断(P<0.05)。结论:肾结石术后尿路感染患者血清SOCS1水平降低,S100A8水平增加,二者联合对肾结石术后尿路感染具有较高的诊断价值。展开更多
基金funded by the National Natural Science Foundation of China(Grant No.82270177)the China Medicine Education Association 2024 Medical Science and Technology Research Project(Grant No.2024KTZ035).
文摘Objective To investigate the effects of calprotectin(S100A8/A9)on the biological activity of acute myeloid leukemia(AML)cells harboring a DNA methyltransferase 3A(DNMT3A)mutation and to explore the underlying molecular mechanisms involved.Methods AML monoclonal cell lines harboring the DNMT3A^(R882H) mutation were generated via lentiviral transduction and limiting dilution.RNA sequencing was used for differential gene expression analysis,followed by bioinformatic pathway enrichment and gene correlation analyses.The biological effects of paquinimod,a selective S100A8/A9 inhibitor,on DNMT3A^(R882H) AML cells were assessed via Cell Counting Kit(CCK-8)proliferation assays,Annexin V/PI staining,cell cycle analysis,cell adhesion assays,and transwell migration assays.Results Differential gene expression analysis revealed 442 upregulated and 535 downregulated genes in DNMT3A-mutated(DNMT3A^(mut))cells compared with those in DNMT3A wild-type(DNMT3A^(wt))cells,with the S100A8/A9 complex recurrently enriched in Reactome pathway analysis.Compared with healthy controls,patients with AML presented increased expression of S100A8 and S100A9 and increased expression of DNMT3A^(mut) cells relative to DNMT3A^(wt) cells,which was correlated with poor prognosis in patients with AML.There were no notable differences in proliferation among the DNMT3A^(mut),DNMT3A^(wt),and empty vector cells under normal or starvation conditions.However,paquinimod treatment notably inhibited the proliferation,migration,and adhesion of DNMT3A^(mut) AML cells in a dose-dependent manner,causing G0/G1 cell cycle arrest,whereas no significant effects on apoptosis were observed.Paquinimod also downregulated key adhesion molecules,including intercellular adhesion molecule 1(ICAM-1),vascular cell adhesion molecule 1(VCAM-1),monocyte chemoattractant protein-1(MCP-1),and matrix metalloproteinase-2(MMP-2).Additionally,S100A8 and S100A9 expression was upregulated in a dose-dependent manner in response to cytarabine treatment.Conclusion Elevated S100A8/A9 expression contributes to the abnormal proliferation,migration,adhesion,and chemoresistance of DNMT3A^(mut) AML cells.Targeting S100A8/A9 alone or in combination with other treatments represents a promising therapeutic strategy for DNMT3A^(mut) AML.
文摘目的:观察蒲公英多糖(dandelion polysaccharide,DP)对大鼠多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)肺、小肠组织炎症反应及S100钙结合蛋白A8/A9(S100 calcium-binding protein A8/A9,S100A8/A9)表达的影响。方法:应用失血性休克及腹腔注射脂多糖“二次打击”的方法,构建大鼠MODS模型,分为假手术组、模型组、DP低剂量组、DP高剂量组。观察各组大鼠肺和小肠脏器系数及湿/干重比值;苏木精-伊红(hematoxylin-eosinstaining,HE)染色观察肺和小肠组织病理形态学改变;免疫组织化学染色观察肺和小肠组织白细胞介素(interleukin,IL)1β、IL-6、IL-10的表达;蛋白质免疫印迹法(Western blot)检测肺和小肠组织S100A8/A9蛋白表达变化。结果:与假手术组相比,模型组大鼠肺脏系数(5.849±0.824)、湿/干重比值(6.556±0.631)和小肠湿/干重比值(6.356±0.535)、湿重/长度比值(73.950±5.569)均上升。HE染色显示肺泡腔及肺间质可见大量炎细胞浸润,肺泡壁增厚;小肠绒毛崩解碎裂,可见炎细胞浸润及节段性集合淋巴滤泡增生。S100A8/A9主要表达于中性粒细胞和巨噬细胞,大鼠肺和小肠组织S100A8/A9、IL-1β、IL-6表达上调,IL-10表达下调。给予高剂量DP治疗后,大鼠肺脏系数(4.297±0.462)、湿/干重比值(5.313±0.495)和小肠湿/干重比值(5.398±0.388)、湿重/长度比值(59.417±2.891)均下降。肺和小肠组织病理损伤减轻,肺和小肠组织S100A8/A9、IL-1β、IL-6表达下调,IL-10表达上调。结论:DP可能通过抑制S100A8/A9的表达,减轻大鼠MODS肺和小肠组织损伤的炎症反应。
文摘目的:探究血清细胞因子信号传导抑制蛋白1(suppressor of cytokine signaling 1,SOCS1)、S100钙结合蛋白A8(S100 calcium binding protein A8,S100A8)对肾结石术后尿路感染的诊断价值。方法:选取2023年4月—2024年4月于南京中医药大学张家港附属医院行输尿管软镜钬激光碎石术后尿路感染的134例肾结石患者为研究对象(尿路感染组),选取本院同期134例行输尿管软镜钬激光碎石术后尿路未感染的肾结石患者为无尿路感染组。采用ELISA法测定血清中SOCS1、S100A8水平。肾结石患者术后尿路感染的影响因素采用logistic回归分析;血清SOCS1、S100A8对肾结石术后尿路感染的诊断价值基于受试者工作特征(receiver operating characteristic,ROC)曲线分析。结果:2组肾结石患者在手术时间、双J管长度、双J管留置时间和结石残留上比较差异有统计学意义(P<0.05);尿路感染组血清SOCS1水平低于无尿路感染组,S100A8水平高于无尿路感染组(P<0.05);多因素logistic回归显示,血清S100A8手术时间大于1 h、双J管长度大于26 cm、双J管留置时间2周以上、结石残留是肾结石术后尿路感染的危险因素,血清SOCS1是肾结石术后尿路感染的保护因素(P<0.05);ROC曲线显示,血清SOCS1、S100A8及二者联合诊断肾结石术后尿路感染的曲线下面积(area under the curve,AUC)分别为0.759、0.816、0.915,两者联合诊断肾结石术后尿路感染的AUC显著高于SOCS1、S100A8单独诊断(P<0.05)。结论:肾结石术后尿路感染患者血清SOCS1水平降低,S100A8水平增加,二者联合对肾结石术后尿路感染具有较高的诊断价值。
