Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regen...Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.展开更多
We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
建立了一种简单、实用的光诱导一锅法高选择性N-甲基喹喔啉酮类化合物和苯乙酮类化合物合成一系列3-烷基化喹唑啉-2(1H)-酮类化合物的方法。该方法在室温条件下,以玫瑰红作为光催化剂,在18 W 460 nm的蓝色LED下照射8 h,通过直接C3-H活...建立了一种简单、实用的光诱导一锅法高选择性N-甲基喹喔啉酮类化合物和苯乙酮类化合物合成一系列3-烷基化喹唑啉-2(1H)-酮类化合物的方法。该方法在室温条件下,以玫瑰红作为光催化剂,在18 W 460 nm的蓝色LED下照射8 h,通过直接C3-H活化的方案,较好收率获得一系列相应的3-烷基化喹喔啉-2(1H)-酮类化合物,最高产率可达到76%。反应体系具有经济实用性和底物适用范围广的特点,为3-烷基化喹喔啉-2(1H)-酮类化合物类化合物的合成提供了一种简便经济的方法。展开更多
目的探讨血清微小核糖核酸-503(miR-503)和微小核糖核酸-520h(miR-520h)对妊娠期糖尿病(GDM)患者并发子痫前期(PE)的诊断价值。方法选取2019年12月至2021年12月于唐山中心医院产科定期产检并建档的GDM患者102例作为研究对象,根据疾病类...目的探讨血清微小核糖核酸-503(miR-503)和微小核糖核酸-520h(miR-520h)对妊娠期糖尿病(GDM)患者并发子痫前期(PE)的诊断价值。方法选取2019年12月至2021年12月于唐山中心医院产科定期产检并建档的GDM患者102例作为研究对象,根据疾病类型分为GDM+PE组(53例)、GDM组(49例)。另选取同期于唐山中心医院进行定期产检并分娩的57例健康孕妇作为正常妊娠组。比较3组糖脂代谢相关指标[甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)、空腹胰岛素(FINS)、空腹血糖(FBG)、餐后2 h血糖(2 h PG)]水平及血清miR-503、miR-520h表达水平、血清胱抑素C(CysC)、同型半胱氨酸(Hcy)水平;比较3组不良妊娠结局。采用多因素Logistic回归分析GDM患者并发PE的危险因素;绘制受试者工作特征(ROC)曲线分析miR-503、miR-520h单独及2项指标联合检测对GDM并发PE的诊断价值。结果3组孕周、年龄、孕前体质量指数、LDL-C水平比较,差异均无统计学意义(P>0.05)。GDM+PE组TC、TG、FFA水平均明显高于GDM组和正常妊娠组,HDL-C水平明显低于GDM组和正常妊娠组,差异均有统计学意义(P<0.05)。GDM组TC、FFA水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组和GDM组FINS、FBG、2 h PG、HbA1c水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组血清miR-503、miR-520h表达水平、CysC和Hcy水平均明显高于GDM组和正常妊娠组,差异均有统计学意义(P<0.05),GDM组血清miR-503、miR-520h表达水平及CysC和Hcy水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组不良妊娠结局总发生率为62.26%(33/53),GDM组为40.82%(20/49),正常妊娠组为10.53%(6/57),GDM+PE组不良妊娠结局总发生率明显高于GDM组和正常妊娠组,差异均有统计学意义(χ^(2)=4.692、32.125,P<0.05),GDM组不良妊娠结局总发生率明显高于正常妊娠组,差异有统计学意义(χ^(2)=13.059,P<0.05)。3组孕妇不良妊娠结局中产后出血、早产或过期产、胎盘早剥、新生儿窒息、宫内生长受限的发生率比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,CysC水平升高、Hcy水平升高、miR-503表达水平升高和miR-520h表达水平升高均为GDM并发PE的危险因素(P<0.05)。ROC曲线分析结果显示,血清miR-503、miR-520h单独及2项指标联合检测诊断GDM并发PE的曲线下面积(AUC)分别为0.755、0.847、0.935,2项指标联合检测的AUC大于miR-503、miR-520h单独检测(Z_(2项联合-miR-503)=4.210、Z_(2项联合-miR-520h)=2.708,P<0.001、0.007)。结论GDM并发PE患者血清miR-503、miR-520h表达水平升高,与妊娠不良结局呈正相关,二者联合检测对诊断GDM并发PE具有重要意义。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271397(to MG),82001293(to MG),82171355(to RX),81971295(to RX)and 81671189(to RX)。
文摘Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
文摘建立了一种简单、实用的光诱导一锅法高选择性N-甲基喹喔啉酮类化合物和苯乙酮类化合物合成一系列3-烷基化喹唑啉-2(1H)-酮类化合物的方法。该方法在室温条件下,以玫瑰红作为光催化剂,在18 W 460 nm的蓝色LED下照射8 h,通过直接C3-H活化的方案,较好收率获得一系列相应的3-烷基化喹喔啉-2(1H)-酮类化合物,最高产率可达到76%。反应体系具有经济实用性和底物适用范围广的特点,为3-烷基化喹喔啉-2(1H)-酮类化合物类化合物的合成提供了一种简便经济的方法。
文摘目的探讨血清微小核糖核酸-503(miR-503)和微小核糖核酸-520h(miR-520h)对妊娠期糖尿病(GDM)患者并发子痫前期(PE)的诊断价值。方法选取2019年12月至2021年12月于唐山中心医院产科定期产检并建档的GDM患者102例作为研究对象,根据疾病类型分为GDM+PE组(53例)、GDM组(49例)。另选取同期于唐山中心医院进行定期产检并分娩的57例健康孕妇作为正常妊娠组。比较3组糖脂代谢相关指标[甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)、空腹胰岛素(FINS)、空腹血糖(FBG)、餐后2 h血糖(2 h PG)]水平及血清miR-503、miR-520h表达水平、血清胱抑素C(CysC)、同型半胱氨酸(Hcy)水平;比较3组不良妊娠结局。采用多因素Logistic回归分析GDM患者并发PE的危险因素;绘制受试者工作特征(ROC)曲线分析miR-503、miR-520h单独及2项指标联合检测对GDM并发PE的诊断价值。结果3组孕周、年龄、孕前体质量指数、LDL-C水平比较,差异均无统计学意义(P>0.05)。GDM+PE组TC、TG、FFA水平均明显高于GDM组和正常妊娠组,HDL-C水平明显低于GDM组和正常妊娠组,差异均有统计学意义(P<0.05)。GDM组TC、FFA水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组和GDM组FINS、FBG、2 h PG、HbA1c水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组血清miR-503、miR-520h表达水平、CysC和Hcy水平均明显高于GDM组和正常妊娠组,差异均有统计学意义(P<0.05),GDM组血清miR-503、miR-520h表达水平及CysC和Hcy水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组不良妊娠结局总发生率为62.26%(33/53),GDM组为40.82%(20/49),正常妊娠组为10.53%(6/57),GDM+PE组不良妊娠结局总发生率明显高于GDM组和正常妊娠组,差异均有统计学意义(χ^(2)=4.692、32.125,P<0.05),GDM组不良妊娠结局总发生率明显高于正常妊娠组,差异有统计学意义(χ^(2)=13.059,P<0.05)。3组孕妇不良妊娠结局中产后出血、早产或过期产、胎盘早剥、新生儿窒息、宫内生长受限的发生率比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,CysC水平升高、Hcy水平升高、miR-503表达水平升高和miR-520h表达水平升高均为GDM并发PE的危险因素(P<0.05)。ROC曲线分析结果显示,血清miR-503、miR-520h单独及2项指标联合检测诊断GDM并发PE的曲线下面积(AUC)分别为0.755、0.847、0.935,2项指标联合检测的AUC大于miR-503、miR-520h单独检测(Z_(2项联合-miR-503)=4.210、Z_(2项联合-miR-520h)=2.708,P<0.001、0.007)。结论GDM并发PE患者血清miR-503、miR-520h表达水平升高,与妊娠不良结局呈正相关,二者联合检测对诊断GDM并发PE具有重要意义。
