The association of retinol binding protein 4 （RBP4） with atherosclerosis of the carotid artery in type 2 diabetes mellitus （T2DM） remains undefined. We aimed to investigate the correlation of RBP4 expression with ...The association of retinol binding protein 4 （RBP4） with atherosclerosis of the carotid artery in type 2 diabetes mellitus （T2DM） remains undefined. We aimed to investigate the correlation of RBP4 expression with atherosclerosis of the carotid artery in T2DM. A total of 1,076 subjects were investigated for intima-media thickness of the bilateral common carotid arteries, and they were divided into three groups： in group Ⅰ, patients had normal neck vascular ultra- sound, in group Ⅱ, intimal carotid artery media thickness was equal to or more than 1 mm, and in group Ⅲ, carotid artery plaque was present. Height, weight, blood pressure （BP）, fasting plasma glucose （FPG）, hemoglobin Alc （HbA1c）, total cholesterol （TC）, triglyceride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipopro- tein cholesterol （HDL-C）, apolipoprotein A-1 （apoA-1）, apolipoprotein B （apoB） and lipoprotein （a） [Lp（a）] were determined by routine laboratory methods. RBP4 and high sensitivity C reactive protein （HsCRP） were measured by an enzyme-linked immuno-sorbent assay, and insulin concentration was measured by an electrochemiluminescence sandwich immunoassay. Duration of diabetes, waist and BP, FPG, HbAlc, TG, TC, LDL-C, APOB, Lp（a）, HsCRP, RBP4 and homeostasis model assessment insulin resistance index （HOMA-IR） were significantly lower in group I than in the other two groups （P〈0.01, P〈0.01）. Plasma levels of HbAlc, RBP4, LDL-C, TC, HOMA-IR, HsCRP and Lp（a）, waist and BP were significantly increased in group III than in group II （P〈0.01）. Multivariate logistic regression analysis showed that there were seven factors associated with the occurrence of carotid artery atherosclero- sis and its risks in descending order were： high LDL-C, high waist, high HsCRP, duration of diabetes, high HOMA-IR, HbAlc and high RBP4. Our finding supported that RBP4 was positively correlated with carotid atherosclerosis in patients with T2DM and could be used as an early predictor of cardiovascular disease.展开更多
We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repet...We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.展开更多
hPFTAIRE1 （PFTK1）, a Cdc2-related protein kinase, is highly expressed in human brain. It exhibits cytoplasmic distribution in Hela cells, although it contains two nuclear localization signals （NLSs） in its N-termi...hPFTAIRE1 （PFTK1）, a Cdc2-related protein kinase, is highly expressed in human brain. It exhibits cytoplasmic distribution in Hela cells, although it contains two nuclear localization signals （NLSs） in its N-terminus. To search for its substrates and regulatory components, we screened a two-hybrid library by using the full-length hPFTAIRE1 as a bait. Four 14-3-3 isoforms （β,ε,η,τ） were identified interacting with the hPFTAIRE1. We found a putative 14-3-3 binding consensus motif（RHSSPSS） in the hPFTAIRE 1, which overlapped with its second NLS. Deletion of the RHSSPSS motif or substitution of Ser^119 gwithAla in the conserved binding motif abolished the specific interaction between the hPFTAIRE 1 and the 14-3 -3 proteins. The mutant S 120A hPFTAIRE1 also showed a weak interaction to the 14-3-3 proteins. The results suggested that the Ser^119 is crucial for the interaction between hPFTAIREI and the 14-3-3 proteins. All the hPFTAIRE1 mutants distributed in cytoplasm of Hela cells and human neuroblastoma cells （SH-SY5Y） when fused to the C-terminus of a green fluorescent protein （GFP）, indicating that binding with the 14-3-3 proteins does not contribute to the subcellular localization of the hPFTAIRE1, although the binding may be involved in its signaling regulation.展开更多
目的研究急性脑梗死患者血清视黄醇结合蛋白(retinol binding protein,RBP)、微小核糖核酸126(microRNA-126,miR-126)、沉默信息调节因子1(silent information regulator1,Sirt1)水平较健康人变化幅度,并分析急性脑梗死患者三个指标水...目的研究急性脑梗死患者血清视黄醇结合蛋白(retinol binding protein,RBP)、微小核糖核酸126(microRNA-126,miR-126)、沉默信息调节因子1(silent information regulator1,Sirt1)水平较健康人变化幅度,并分析急性脑梗死患者三个指标水平变化与颈动脉粥样硬化斑块稳定性的相关性。方法选取来我院就诊的急性脑梗死患者140例为病例组,另选同期健康体检者60例为对照组,病例组患者行彩色多普勒超声检查,据超声结果分为稳定斑块组(n=78)和不稳定斑块组(n=62)。收集研究对象的临床资料;酶联免疫吸附试验检测血清RBP、Sirt1表达;实时荧光定量PCR法检测血清miR-126表达;Spearman分析患者血清RBP、miR-126、Sirt1表达与颈动脉粥样硬化斑块稳定性的关系;受试者工作特征曲线分析患者血清RBP、miR-126、Sirt1表达对颈动脉粥样硬化斑块稳定性的预测价值。结果病例组患者血清RBP表达较对照组增加,miR-126、Sirt1表达较对照组降低(P<0.05);不稳定斑块组血清RBP表达较稳定斑块组增加,miR-126、Sirt1表达较稳定斑块组降低(P<0.05);血清RBP表达与颈动脉粥样硬化斑块稳定性存在正相关关系(r=0.423,P<0.05),血清miR-126、Sirt1表达与颈动脉粥样硬化斑块稳定性存在负相关关系(r=-0.514、-0.366,P<0.05);RBP、miR-126、Sirt1及联合预测的AUC为0.746、0.798、0.712、0.892,敏感度为59.7%、75.8%、75.8%、74.2%,特异度为84.6%、70.5%、64.1%、92.3%,三指标联合预测颈动脉粥样硬化斑块稳定性的价值好于单一预测价值。结论急性脑梗死患者血清RBP表达增加,miR-126、Sirt1表达降低,与颈动脉粥样硬化斑块稳定性相关,血清RBP、miR-126、Sirt1对颈动脉粥样硬化斑块稳定性具有较好的预测价值。展开更多
This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed ...This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)within both the patient tissue specimens and glioblastoma cell lines.The relationship between lncRNA DPP10-AS1 expression in glioblastoma and patient prognosis was investigated.Cell Counting Kit-8(CCK-8),transwell,and clonogenic experiments were utilized to assess tumor cells’proliferation,invasiveness,and migratory potentials after lncRNA DPP10-AS1 expression was up or down-regulated.Using an online bioinformatics prediction tool,the intracellular localization of lncRNA DPP10-AS1 and its target miRNA were predicted,and RNA-FISH verified results.A dual-luciferase reporter experiment validated the relationship across miR-24-3p together with lncRNA DPP10-AS1.MiR-24-3p expression within glioblastoma was identified through RT-qPCR,and potential link across miR-24-3p and lncRNA DPP10-AS1 was assessed using Pearson correlation analysis.Moreover,influence from lncRNA DPP10-AS1/miR-24-3p axis upon glioblastoma cell progression was assessed in vivo via a subcutaneous xenograft tumor model.Results:The expression of lncRNA DPP10-AS1 was notably reduced in both surgical specimens of glioblastoma and the equivalent cell lines.Low level of lncRNA DPP10-AS1 in glioblastoma is following poor prognosis.The downregulation of lncRNA DPP10-AS1 in glioblastoma cells resulted in enhanced cellular proliferation,migration,and invasion capabilities,accompanied by downregulated E-cadherin and upregulated vimentin and N-cadherin.Additionally,the observed upregulation of lncRNA DPP10-AS1 demonstrated a substantial inhibitory function upon proliferation,invasion,and migratory capabilities of LN229 cells.Subcellular localization disclosed that lncRNA DPP10-AS1 had a binding site that interacted with miR-24-3p.Upregulated miR-24-3p was detected in glioblastomas,displaying an inverse correlation with lncRNA DPP10-AS1 expression.MiR-24-3p downstream target has been determined as chromodomain helicase DNA binding protein 5(CHD5).LncRNA DPP10-AS1 affected the invasion and proliferation of glioblastoma by controlling the miR-24-3p/CHD5 axis.Conclusion:The present study demonstrated that lncRNA DPP10-AS1 can inhibit the invasive,migratory,and proliferative properties of glioblastoma by regulating the miR-24-3p/CHD5 signaling pathway.Consequently,lncRNA DPP10-AS1 has potential as a tumor suppressor and might be utilized for accurate diagnosis and targeted treatments of glioblastomas.展开更多
文摘The association of retinol binding protein 4 （RBP4） with atherosclerosis of the carotid artery in type 2 diabetes mellitus （T2DM） remains undefined. We aimed to investigate the correlation of RBP4 expression with atherosclerosis of the carotid artery in T2DM. A total of 1,076 subjects were investigated for intima-media thickness of the bilateral common carotid arteries, and they were divided into three groups： in group Ⅰ, patients had normal neck vascular ultra- sound, in group Ⅱ, intimal carotid artery media thickness was equal to or more than 1 mm, and in group Ⅲ, carotid artery plaque was present. Height, weight, blood pressure （BP）, fasting plasma glucose （FPG）, hemoglobin Alc （HbA1c）, total cholesterol （TC）, triglyceride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipopro- tein cholesterol （HDL-C）, apolipoprotein A-1 （apoA-1）, apolipoprotein B （apoB） and lipoprotein （a） [Lp（a）] were determined by routine laboratory methods. RBP4 and high sensitivity C reactive protein （HsCRP） were measured by an enzyme-linked immuno-sorbent assay, and insulin concentration was measured by an electrochemiluminescence sandwich immunoassay. Duration of diabetes, waist and BP, FPG, HbAlc, TG, TC, LDL-C, APOB, Lp（a）, HsCRP, RBP4 and homeostasis model assessment insulin resistance index （HOMA-IR） were significantly lower in group I than in the other two groups （P〈0.01, P〈0.01）. Plasma levels of HbAlc, RBP4, LDL-C, TC, HOMA-IR, HsCRP and Lp（a）, waist and BP were significantly increased in group III than in group II （P〈0.01）. Multivariate logistic regression analysis showed that there were seven factors associated with the occurrence of carotid artery atherosclero- sis and its risks in descending order were： high LDL-C, high waist, high HsCRP, duration of diabetes, high HOMA-IR, HbAlc and high RBP4. Our finding supported that RBP4 was positively correlated with carotid atherosclerosis in patients with T2DM and could be used as an early predictor of cardiovascular disease.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBSS00047(to PL)the National Natural Science Foundation of China,Nos.82072166(to PL),82071394(to XG)+4 种基金Science and Technology Planning Project of Tianjin,No.20YFZCSY00030(to PL)Science and Technology Project of Tianjin Municipal Health Commission,No.TJWJ2021QN005(to XG)Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-006ATianjin Municipal Education Commission Scientific Research Program Project,No.2020KJ164(to JZ)China Postdoctoral Science Foundation,No.2022M712392(to ZY).
文摘We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.
基金grants from National Natural Science Foundation of China （Nos. 30400073 ,30330010）.
文摘hPFTAIRE1 （PFTK1）, a Cdc2-related protein kinase, is highly expressed in human brain. It exhibits cytoplasmic distribution in Hela cells, although it contains two nuclear localization signals （NLSs） in its N-terminus. To search for its substrates and regulatory components, we screened a two-hybrid library by using the full-length hPFTAIRE1 as a bait. Four 14-3-3 isoforms （β,ε,η,τ） were identified interacting with the hPFTAIRE1. We found a putative 14-3-3 binding consensus motif（RHSSPSS） in the hPFTAIRE 1, which overlapped with its second NLS. Deletion of the RHSSPSS motif or substitution of Ser^119 gwithAla in the conserved binding motif abolished the specific interaction between the hPFTAIRE 1 and the 14-3 -3 proteins. The mutant S 120A hPFTAIRE1 also showed a weak interaction to the 14-3-3 proteins. The results suggested that the Ser^119 is crucial for the interaction between hPFTAIREI and the 14-3-3 proteins. All the hPFTAIRE1 mutants distributed in cytoplasm of Hela cells and human neuroblastoma cells （SH-SY5Y） when fused to the C-terminus of a green fluorescent protein （GFP）, indicating that binding with the 14-3-3 proteins does not contribute to the subcellular localization of the hPFTAIRE1, although the binding may be involved in its signaling regulation.
文摘目的研究急性脑梗死患者血清视黄醇结合蛋白(retinol binding protein,RBP)、微小核糖核酸126(microRNA-126,miR-126)、沉默信息调节因子1(silent information regulator1,Sirt1)水平较健康人变化幅度,并分析急性脑梗死患者三个指标水平变化与颈动脉粥样硬化斑块稳定性的相关性。方法选取来我院就诊的急性脑梗死患者140例为病例组,另选同期健康体检者60例为对照组,病例组患者行彩色多普勒超声检查,据超声结果分为稳定斑块组(n=78)和不稳定斑块组(n=62)。收集研究对象的临床资料;酶联免疫吸附试验检测血清RBP、Sirt1表达;实时荧光定量PCR法检测血清miR-126表达;Spearman分析患者血清RBP、miR-126、Sirt1表达与颈动脉粥样硬化斑块稳定性的关系;受试者工作特征曲线分析患者血清RBP、miR-126、Sirt1表达对颈动脉粥样硬化斑块稳定性的预测价值。结果病例组患者血清RBP表达较对照组增加,miR-126、Sirt1表达较对照组降低(P<0.05);不稳定斑块组血清RBP表达较稳定斑块组增加,miR-126、Sirt1表达较稳定斑块组降低(P<0.05);血清RBP表达与颈动脉粥样硬化斑块稳定性存在正相关关系(r=0.423,P<0.05),血清miR-126、Sirt1表达与颈动脉粥样硬化斑块稳定性存在负相关关系(r=-0.514、-0.366,P<0.05);RBP、miR-126、Sirt1及联合预测的AUC为0.746、0.798、0.712、0.892,敏感度为59.7%、75.8%、75.8%、74.2%,特异度为84.6%、70.5%、64.1%、92.3%,三指标联合预测颈动脉粥样硬化斑块稳定性的价值好于单一预测价值。结论急性脑梗死患者血清RBP表达增加,miR-126、Sirt1表达降低,与颈动脉粥样硬化斑块稳定性相关,血清RBP、miR-126、Sirt1对颈动脉粥样硬化斑块稳定性具有较好的预测价值。
基金supported through the Natural Science Foundation of Jiangsu Province(No.BK20201172)the Key Project of the Jiangsu Health Commission(No.ZDB2020016)the Jiangsu Province Key Research and Development Program:Social Development Project(No.BE2021653).
文摘This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)within both the patient tissue specimens and glioblastoma cell lines.The relationship between lncRNA DPP10-AS1 expression in glioblastoma and patient prognosis was investigated.Cell Counting Kit-8(CCK-8),transwell,and clonogenic experiments were utilized to assess tumor cells’proliferation,invasiveness,and migratory potentials after lncRNA DPP10-AS1 expression was up or down-regulated.Using an online bioinformatics prediction tool,the intracellular localization of lncRNA DPP10-AS1 and its target miRNA were predicted,and RNA-FISH verified results.A dual-luciferase reporter experiment validated the relationship across miR-24-3p together with lncRNA DPP10-AS1.MiR-24-3p expression within glioblastoma was identified through RT-qPCR,and potential link across miR-24-3p and lncRNA DPP10-AS1 was assessed using Pearson correlation analysis.Moreover,influence from lncRNA DPP10-AS1/miR-24-3p axis upon glioblastoma cell progression was assessed in vivo via a subcutaneous xenograft tumor model.Results:The expression of lncRNA DPP10-AS1 was notably reduced in both surgical specimens of glioblastoma and the equivalent cell lines.Low level of lncRNA DPP10-AS1 in glioblastoma is following poor prognosis.The downregulation of lncRNA DPP10-AS1 in glioblastoma cells resulted in enhanced cellular proliferation,migration,and invasion capabilities,accompanied by downregulated E-cadherin and upregulated vimentin and N-cadherin.Additionally,the observed upregulation of lncRNA DPP10-AS1 demonstrated a substantial inhibitory function upon proliferation,invasion,and migratory capabilities of LN229 cells.Subcellular localization disclosed that lncRNA DPP10-AS1 had a binding site that interacted with miR-24-3p.Upregulated miR-24-3p was detected in glioblastomas,displaying an inverse correlation with lncRNA DPP10-AS1 expression.MiR-24-3p downstream target has been determined as chromodomain helicase DNA binding protein 5(CHD5).LncRNA DPP10-AS1 affected the invasion and proliferation of glioblastoma by controlling the miR-24-3p/CHD5 axis.Conclusion:The present study demonstrated that lncRNA DPP10-AS1 can inhibit the invasive,migratory,and proliferative properties of glioblastoma by regulating the miR-24-3p/CHD5 signaling pathway.Consequently,lncRNA DPP10-AS1 has potential as a tumor suppressor and might be utilized for accurate diagnosis and targeted treatments of glioblastomas.
