BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity.During osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased abil...BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity.During osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts,resulting in bone loss.Jumonji domain-containing 1C(JMJD1C)has been demonstrated to suppress osteoclastogenesis.AIM To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying mechanism.METHODS BMSCs were isolated from mouse bone marrow tissues.Oil Red O staining,Alizarin red staining,alkaline phosphatase staining and the expression of adipo-genic and osteogenic-associated genes were assessed to determine the differen-tiation of BMSCs.Bone marrow-derived macrophages(BMMs)were incubated with receptor activator of nuclear factor-kappaΒligand to induce osteoclast differentiation,and osteoclast differen-tiation was confirmed by tartrate-resistant acid phosphatase staining.Other related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western blotting.Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6 and interleukin-1 beta.RESULTS The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated.JMJD1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction,while p-nuclear factor-κB(NF-κB)and inflammatory cytokines were not significantly altered.Knockdown of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in BMSCs.Moreover,JMJD1C expression decreased during BMM osteoclast differentiation.CONCLUSION The JMJD1C/NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.展开更多
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of A...In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.展开更多
目的:探讨YB-1(Y-box binding protein 1)在青年型乳腺癌组织中的表达及意义。方法:应用免疫组织化学方法研究YB-1蛋白在青年型乳腺癌组织中的表达,并结合病理组织学类型、病理分级等临床特征分析YB-1在青年型乳腺癌组织中的表达意义;依...目的:探讨YB-1(Y-box binding protein 1)在青年型乳腺癌组织中的表达及意义。方法:应用免疫组织化学方法研究YB-1蛋白在青年型乳腺癌组织中的表达,并结合病理组织学类型、病理分级等临床特征分析YB-1在青年型乳腺癌组织中的表达意义;依据ER、PR、HER-2、CK5/6表达对青年型乳腺癌进行分子分型(Luminal-A、Luminal-B、HER2+和Basal-like 4个分子亚型),并分析其与YB-1表达的关系。结果:HE结果显示64例青年型乳腺癌病理组织学分类主要为浸润性导管癌,占59.4%。免疫组化结果显示64例青年型乳腺癌组织中YB-1阳性率为92.2%,其中细胞核阳性表达率53.1%,细胞浆阳性表达率39.1%。肿瘤>2cm的患者占59.4%,YB-1主要表达在细胞核(40.6%),患者肿瘤?2cm占37.5%,YB-1则主要在细胞浆表达(20.3%),YB-1表达类型与肿瘤大小有显著统计学意义(P=0.036)。组织学3级所占比例最高,占48.4%,且多为YB-1细胞核表达(37.5%),乳腺癌不同的组织学分级间YB-1的表达率不同(P=0.000);青年型乳腺癌患者发生淋巴结转移的比例高(84.4%),其中N3期所占比例最高,占40.6%,YB-1主要在细胞核表达,占31.3%,胞浆表达占7.8%。青年型乳腺癌分子分型中主最多见的是Luminal-B型,占46.9%,YB-1主要表达在细胞核(32.8%),浆表达仅占9.4%,统计分析显示YB-1表达的核浆分布特点与青年型乳腺癌分子分型有关(P=0.04)。结论:YB-1在青年型乳腺癌组织中的表达特点与肿瘤大小、病理组织分级及淋巴结状态有一定关系,细胞核阳性主要见于肿瘤>2cm的患者,而细胞浆阳性主要见于肿瘤?2cm的患者,且YB-1细胞核表达主要为组织学3级,且青年型乳腺癌淋巴结转移率高,YB-1主要在细胞核表达;青年型乳腺癌不同分子分型中YB-1蛋白表达存在差异,YB-1可能成为青年型乳腺癌防治的新的分子靶点。展开更多
基金2018 Henan Medical Science and Technology Research Plan Project,China,No.SBGJ2018019.
文摘BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity.During osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts,resulting in bone loss.Jumonji domain-containing 1C(JMJD1C)has been demonstrated to suppress osteoclastogenesis.AIM To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying mechanism.METHODS BMSCs were isolated from mouse bone marrow tissues.Oil Red O staining,Alizarin red staining,alkaline phosphatase staining and the expression of adipo-genic and osteogenic-associated genes were assessed to determine the differen-tiation of BMSCs.Bone marrow-derived macrophages(BMMs)were incubated with receptor activator of nuclear factor-kappaΒligand to induce osteoclast differentiation,and osteoclast differen-tiation was confirmed by tartrate-resistant acid phosphatase staining.Other related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western blotting.Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6 and interleukin-1 beta.RESULTS The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated.JMJD1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction,while p-nuclear factor-κB(NF-κB)and inflammatory cytokines were not significantly altered.Knockdown of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in BMSCs.Moreover,JMJD1C expression decreased during BMM osteoclast differentiation.CONCLUSION The JMJD1C/NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
基金supported by STI2030-Major Projects,No.2021ZD 0201801(to JG)Shanxi Province Basic Research Program,No.20210302123429(to QS).
文摘In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.
文摘目的:探讨YB-1(Y-box binding protein 1)在青年型乳腺癌组织中的表达及意义。方法:应用免疫组织化学方法研究YB-1蛋白在青年型乳腺癌组织中的表达,并结合病理组织学类型、病理分级等临床特征分析YB-1在青年型乳腺癌组织中的表达意义;依据ER、PR、HER-2、CK5/6表达对青年型乳腺癌进行分子分型(Luminal-A、Luminal-B、HER2+和Basal-like 4个分子亚型),并分析其与YB-1表达的关系。结果:HE结果显示64例青年型乳腺癌病理组织学分类主要为浸润性导管癌,占59.4%。免疫组化结果显示64例青年型乳腺癌组织中YB-1阳性率为92.2%,其中细胞核阳性表达率53.1%,细胞浆阳性表达率39.1%。肿瘤>2cm的患者占59.4%,YB-1主要表达在细胞核(40.6%),患者肿瘤?2cm占37.5%,YB-1则主要在细胞浆表达(20.3%),YB-1表达类型与肿瘤大小有显著统计学意义(P=0.036)。组织学3级所占比例最高,占48.4%,且多为YB-1细胞核表达(37.5%),乳腺癌不同的组织学分级间YB-1的表达率不同(P=0.000);青年型乳腺癌患者发生淋巴结转移的比例高(84.4%),其中N3期所占比例最高,占40.6%,YB-1主要在细胞核表达,占31.3%,胞浆表达占7.8%。青年型乳腺癌分子分型中主最多见的是Luminal-B型,占46.9%,YB-1主要表达在细胞核(32.8%),浆表达仅占9.4%,统计分析显示YB-1表达的核浆分布特点与青年型乳腺癌分子分型有关(P=0.04)。结论:YB-1在青年型乳腺癌组织中的表达特点与肿瘤大小、病理组织分级及淋巴结状态有一定关系,细胞核阳性主要见于肿瘤>2cm的患者,而细胞浆阳性主要见于肿瘤?2cm的患者,且YB-1细胞核表达主要为组织学3级,且青年型乳腺癌淋巴结转移率高,YB-1主要在细胞核表达;青年型乳腺癌不同分子分型中YB-1蛋白表达存在差异,YB-1可能成为青年型乳腺癌防治的新的分子靶点。
