为深入探究小麦胚芽中的脂质成分,该研究采用不同溶剂分别提取小麦胚芽中的磷脂和中性脂质,利用核磁共振技术(nuclear magnetic resonance,NMR)对小麦胚芽中的脂质成分进行分析,结果表明:^(31)P NMR在小麦胚芽中检测到6种磷脂和相对应的...为深入探究小麦胚芽中的脂质成分,该研究采用不同溶剂分别提取小麦胚芽中的磷脂和中性脂质,利用核磁共振技术(nuclear magnetic resonance,NMR)对小麦胚芽中的脂质成分进行分析,结果表明:^(31)P NMR在小麦胚芽中检测到6种磷脂和相对应的5种溶血性磷脂,以及非脂质含磷化合物甘油磷脂酰胆碱(GPC);磷脂中含量最高的是磷脂酰胆碱(PC),其摩尔浓度为0.42μmol/g,摩尔分数为28.50%,质量浓度为0.31 mg/g,质量分数为30.20%;^(1)H NMR测定小麦胚芽中的多种中性脂质组成及含量,包括甘油三酯(TG)、甘油二酯(DG)、甘油单酯(MG)和游离脂肪酸(FA),其中含量最高的甘油酯是TG,占比为77.25%,含量最低的是2-甘油单酯(2-MG),占比为0.03%;小麦胚芽的甘油三酯和磷脂中检测出亚油酸(L)、油酸(O)和亚麻酸(Ln)等6种不饱和脂肪酸,其中亚油酸的含量最高,在甘油三酯中占比56.26%,在磷脂中占比45.37%。溶血性磷脂和GPC是磷脂的水解产物,DG、MG和FA是甘油三酯的水解产物,这些物质可以反映样品中脂质的水解程度。研究结果表明,利用NMR不仅能够对小麦胚芽脂质的组分进行定性定量分析,而且可以监测小麦胚芽脂质水解程度的变化。NMR技术在小麦胚芽相关产品的脂质分析研究具有重要作用。展开更多
目的探讨H3.3G34W、p63及SATB2在骨巨细胞瘤(giant cell tumor of bone,GCTB)中的表达情况及其联合应用对GCTB的诊断作用和价值。方法收集西安交通大学附属红会医院病理科2020年至2022年诊断的54例GCTB、83例非骨巨细胞瘤(non-giant cel...目的探讨H3.3G34W、p63及SATB2在骨巨细胞瘤(giant cell tumor of bone,GCTB)中的表达情况及其联合应用对GCTB的诊断作用和价值。方法收集西安交通大学附属红会医院病理科2020年至2022年诊断的54例GCTB、83例非骨巨细胞瘤(non-giant cell tumor of bone,NGCTB)(包含14例动脉瘤样骨囊肿、16例软骨母细胞瘤和53例非骨化性纤维瘤)患者的样本和病历资料,采用免疫组织化学EliVision法检测H3.3G34W、p63及SATB2的表达情况。通过χ^(2)检验判断H3.3G34W、p63及SATB2的阳性率在各组间是否存在统计学差异;通过Logistic回归分析建立包括H3.3G34W、p63及SATB2的联合诊断模型,通过受试者工作特征(ROC)曲线分析评价模型的诊断价值。结果H3.3G34W、p63及SATB2在GCTB组中阳性率分别为81.5%、90.7%、92.6%;在NGCTB组中阳性率分别为2.4%、28.9%、62.7%。与NGCTB组相比,GCTB组患者年龄显著较大[(41.222±14.849)vs.(16.566±9.439);P<0.001],女性比男性患病率更高(51.9%vs.48.1%,P<0.001)。与NGCTB组相比,GCTB组中H3.3G34W(81.5%vs.2.4%,P<0.001);p63(90.7%vs.28.9%,P<0.001)和SATB2(92.6%vs.62.7%,P<0.001)的阳性率更高。单因素Logistic回归分析构建单因素预测模型,同时行ROC曲线分析,表明年龄(AUC=92.9%,P<0.001)、性别(AUC=64.5%,P=0.004)、H3.3G34W阳性率(AUC=89.5%,P<0.001)、p63阳性率(AUC=80.9%,P<0.001)、SATB2阳性率(AUC=65.0%,P=0.003)是GCTB诊断的独立预测因素。进一步的多因素Logistic回归分析构建混合预测模型,并行ROC曲线分析,发现混合模型展现出比单因素模型更好的预测价值(AUC=98.4%,P<0.001)。结论H3.3G34W、p63及SATB2是有效诊断GCTB的分子标记物,且三者联合应用更能提高GCTB的诊断预测效能。展开更多
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
Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of bo...Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely unknown.The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC management.Methods Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol.RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)cells.The upregulated genes were analyzed by GO and KEGG analyses.Then,qPCR and Western blotting were employed to determine the relative gene expression levels.Afterwards,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow cytometry.Results PLC-LR and Hep3B-LR were established.There was a total of 116 significantly upregulated genes common to both LR cell lines.The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species pathways.Notably,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib resistance.The high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the apoptosis.The combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR cells.Conclusion The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.展开更多
文摘目的探讨H3.3G34W、p63及SATB2在骨巨细胞瘤(giant cell tumor of bone,GCTB)中的表达情况及其联合应用对GCTB的诊断作用和价值。方法收集西安交通大学附属红会医院病理科2020年至2022年诊断的54例GCTB、83例非骨巨细胞瘤(non-giant cell tumor of bone,NGCTB)(包含14例动脉瘤样骨囊肿、16例软骨母细胞瘤和53例非骨化性纤维瘤)患者的样本和病历资料,采用免疫组织化学EliVision法检测H3.3G34W、p63及SATB2的表达情况。通过χ^(2)检验判断H3.3G34W、p63及SATB2的阳性率在各组间是否存在统计学差异;通过Logistic回归分析建立包括H3.3G34W、p63及SATB2的联合诊断模型,通过受试者工作特征(ROC)曲线分析评价模型的诊断价值。结果H3.3G34W、p63及SATB2在GCTB组中阳性率分别为81.5%、90.7%、92.6%;在NGCTB组中阳性率分别为2.4%、28.9%、62.7%。与NGCTB组相比,GCTB组患者年龄显著较大[(41.222±14.849)vs.(16.566±9.439);P<0.001],女性比男性患病率更高(51.9%vs.48.1%,P<0.001)。与NGCTB组相比,GCTB组中H3.3G34W(81.5%vs.2.4%,P<0.001);p63(90.7%vs.28.9%,P<0.001)和SATB2(92.6%vs.62.7%,P<0.001)的阳性率更高。单因素Logistic回归分析构建单因素预测模型,同时行ROC曲线分析,表明年龄(AUC=92.9%,P<0.001)、性别(AUC=64.5%,P=0.004)、H3.3G34W阳性率(AUC=89.5%,P<0.001)、p63阳性率(AUC=80.9%,P<0.001)、SATB2阳性率(AUC=65.0%,P=0.003)是GCTB诊断的独立预测因素。进一步的多因素Logistic回归分析构建混合预测模型,并行ROC曲线分析,发现混合模型展现出比单因素模型更好的预测价值(AUC=98.4%,P<0.001)。结论H3.3G34W、p63及SATB2是有效诊断GCTB的分子标记物,且三者联合应用更能提高GCTB的诊断预测效能。
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.
基金supported by the Global Select Project(No.DJK-LX-2022001)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely unknown.The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC management.Methods Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol.RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)cells.The upregulated genes were analyzed by GO and KEGG analyses.Then,qPCR and Western blotting were employed to determine the relative gene expression levels.Afterwards,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow cytometry.Results PLC-LR and Hep3B-LR were established.There was a total of 116 significantly upregulated genes common to both LR cell lines.The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species pathways.Notably,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib resistance.The high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the apoptosis.The combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR cells.Conclusion The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.
