Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
目的探究血清叉头盒蛋白M1(forkhead box protein M1,FOXM1)和胰岛素样生长因子2(insulin-like growth factor 2,IGF2)表达对老年心力衰竭合并肺炎患者预后的预测价值。方法将邯郸市中心医院2021年3月~2022年6月收治的126例老年心力衰...目的探究血清叉头盒蛋白M1(forkhead box protein M1,FOXM1)和胰岛素样生长因子2(insulin-like growth factor 2,IGF2)表达对老年心力衰竭合并肺炎患者预后的预测价值。方法将邯郸市中心医院2021年3月~2022年6月收治的126例老年心力衰竭并发肺炎患者设为病例组,并根据随访情况将122例患者分为预后不良组(n=33)和预后良好组(n=89),另选取该院同期126例健康体检者为对照组。检测两组(病例组和对照组)血清FOXM1和IGF2水平,检测病例组用力肺活量(forced vital capacity,FVC)和第一秒用力呼容积(forced expiratory volume in one second,FEV1)。采用Spearman分析法分析老年心力衰竭并发肺炎患者血清FOXM1和IGF2水平与心功能分级的相关性;受试者工作特征(receiver operating characteristic,ROC)曲线分析血清FOXM1和IGF2水平对老年心力衰竭并发肺炎患者预后的预测价值。结果与对照组比较,病例组血清FOXM1(2.39±0.55 vs 1.06±0.21)和IGF2(71.33±7.96pg/ml vs 47.82±5.14pg/ml)水平明显较高,差异有统计学意义(t=25.358,27.581,均P<0.05);与预后良好组比较,预后不良组血清FOXM1(3.87±1.06 vs 1.95±0.51)和IGF2水平(85.88±9.54pg/ml vs 69.14±8.73pg/ml)明显较高,差异具有统计学意义(t=13.453,9.174,均P<0.05);预后良好组和预后不良组心功能分级比较差异有统计学意义(χ^(2)=7.120,P<0.05),且与预后不良组比较,预后良好组FEV1(1.24±0.32L vs 1.08±0.25L)和FEV1/FVC(55.46%±5.77%vs 52.30%±5.38%)明显较高,差异有统计学意义(t=2.592,2.735,均P<0.05);老年心力衰竭并发肺炎患者血清FOXM1水平和IGF2水平与心功能分级呈显著正相关(r=0.496,0.517,均P<0.05)。ROC曲线结果显示,血清FOXM1单独预测老年心力衰竭并发肺炎患者预后的曲线下面积(area under the curve,AUC)为0.854(95CI%:0.779~0.912),其敏感度、特异度分别为75.76%,86.52%,最佳截断值为2.75;IGF2单独预测老年心力衰竭并发肺炎患者预后的AUC为0.874(95CI%:0.802~0.927),其敏感度、特异度分别为72.73%,85.39%,最佳截断值为78.30 pg/ml;二者联合预测老年心力衰竭并发肺炎患者预后的AUC显著大于血清FOXM1和IGF2单独诊断的AUC(Z=2.413,2.737,P=0.006,0.016)。结论血清FOXM1和IGF2水平在老年心力衰竭并发肺炎患者中升高,且二者联合检测对患者预后具有较高的预测价值。展开更多
Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood cl...Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development.Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke.Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after stroke.FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully explored.Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36.Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage.FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)gene.In this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.展开更多
巨噬细胞具有较强的可塑性与异质性,可针对不同信号刺激发生功能转化,如转化为经典激活M1型(即M1型极化)、选择性激活M2型(即M2型极化)等。巨噬细胞M1/M2型极化的途径较为广泛,涉及核因子-κB(nuclear factor-κB,NF-κB)/丝裂原活化蛋...巨噬细胞具有较强的可塑性与异质性,可针对不同信号刺激发生功能转化,如转化为经典激活M1型(即M1型极化)、选择性激活M2型(即M2型极化)等。巨噬细胞M1/M2型极化的途径较为广泛,涉及核因子-κB(nuclear factor-κB,NF-κB)/丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、白细胞介素-4(interleukin-4,IL-4)/信号转导与转录激活因子6(signal transduction and activator of transcription 6,STAT6)信号通路、Notch信号通路、无翼样糖蛋白/β-连环蛋白(Wnt/β-catenin)信号通路等。同时,巨噬细胞M1/M2型极化可不同程度地受到外泌体、代谢物、非编码RNA、电刺激、益生菌等的功能调节,其失衡与不同类型肝病的发生、发展关系密切。该文通过对该极化的作用机制进行梳理,发现巨噬细胞M1型极化在肝组织损伤、炎症反应及纤维化进程中起助推作用,巨噬细胞M2型极化则相反;其中,肝癌作为慢性肝病的晚期阶段,以巨噬细胞M2型极化增强、巨噬细胞M1型极化受损为特征。因此,该文关注巨噬细胞M1/M2型极化在不同类型肝病中的作用,以期能更好地确立巨噬细胞亚群靶向疗法。展开更多
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
文摘目的探究血清叉头盒蛋白M1(forkhead box protein M1,FOXM1)和胰岛素样生长因子2(insulin-like growth factor 2,IGF2)表达对老年心力衰竭合并肺炎患者预后的预测价值。方法将邯郸市中心医院2021年3月~2022年6月收治的126例老年心力衰竭并发肺炎患者设为病例组,并根据随访情况将122例患者分为预后不良组(n=33)和预后良好组(n=89),另选取该院同期126例健康体检者为对照组。检测两组(病例组和对照组)血清FOXM1和IGF2水平,检测病例组用力肺活量(forced vital capacity,FVC)和第一秒用力呼容积(forced expiratory volume in one second,FEV1)。采用Spearman分析法分析老年心力衰竭并发肺炎患者血清FOXM1和IGF2水平与心功能分级的相关性;受试者工作特征(receiver operating characteristic,ROC)曲线分析血清FOXM1和IGF2水平对老年心力衰竭并发肺炎患者预后的预测价值。结果与对照组比较,病例组血清FOXM1(2.39±0.55 vs 1.06±0.21)和IGF2(71.33±7.96pg/ml vs 47.82±5.14pg/ml)水平明显较高,差异有统计学意义(t=25.358,27.581,均P<0.05);与预后良好组比较,预后不良组血清FOXM1(3.87±1.06 vs 1.95±0.51)和IGF2水平(85.88±9.54pg/ml vs 69.14±8.73pg/ml)明显较高,差异具有统计学意义(t=13.453,9.174,均P<0.05);预后良好组和预后不良组心功能分级比较差异有统计学意义(χ^(2)=7.120,P<0.05),且与预后不良组比较,预后良好组FEV1(1.24±0.32L vs 1.08±0.25L)和FEV1/FVC(55.46%±5.77%vs 52.30%±5.38%)明显较高,差异有统计学意义(t=2.592,2.735,均P<0.05);老年心力衰竭并发肺炎患者血清FOXM1水平和IGF2水平与心功能分级呈显著正相关(r=0.496,0.517,均P<0.05)。ROC曲线结果显示,血清FOXM1单独预测老年心力衰竭并发肺炎患者预后的曲线下面积(area under the curve,AUC)为0.854(95CI%:0.779~0.912),其敏感度、特异度分别为75.76%,86.52%,最佳截断值为2.75;IGF2单独预测老年心力衰竭并发肺炎患者预后的AUC为0.874(95CI%:0.802~0.927),其敏感度、特异度分别为72.73%,85.39%,最佳截断值为78.30 pg/ml;二者联合预测老年心力衰竭并发肺炎患者预后的AUC显著大于血清FOXM1和IGF2单独诊断的AUC(Z=2.413,2.737,P=0.006,0.016)。结论血清FOXM1和IGF2水平在老年心力衰竭并发肺炎患者中升高,且二者联合检测对患者预后具有较高的预测价值。
基金supported in part by the National Institutes of Health grant 5R01NS117364-02(to JT)。
文摘Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development.Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke.Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after stroke.FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully explored.Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36.Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage.FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)gene.In this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.
文摘巨噬细胞具有较强的可塑性与异质性,可针对不同信号刺激发生功能转化,如转化为经典激活M1型(即M1型极化)、选择性激活M2型(即M2型极化)等。巨噬细胞M1/M2型极化的途径较为广泛,涉及核因子-κB(nuclear factor-κB,NF-κB)/丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、白细胞介素-4(interleukin-4,IL-4)/信号转导与转录激活因子6(signal transduction and activator of transcription 6,STAT6)信号通路、Notch信号通路、无翼样糖蛋白/β-连环蛋白(Wnt/β-catenin)信号通路等。同时,巨噬细胞M1/M2型极化可不同程度地受到外泌体、代谢物、非编码RNA、电刺激、益生菌等的功能调节,其失衡与不同类型肝病的发生、发展关系密切。该文通过对该极化的作用机制进行梳理,发现巨噬细胞M1型极化在肝组织损伤、炎症反应及纤维化进程中起助推作用,巨噬细胞M2型极化则相反;其中,肝癌作为慢性肝病的晚期阶段,以巨噬细胞M2型极化增强、巨噬细胞M1型极化受损为特征。因此,该文关注巨噬细胞M1/M2型极化在不同类型肝病中的作用,以期能更好地确立巨噬细胞亚群靶向疗法。
