BACKGROUND The intricate relationship between type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)presents a challenge in understanding the significance of various biomarkers in diagnosis.AIM To elucidate the ro...BACKGROUND The intricate relationship between type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)presents a challenge in understanding the significance of various biomarkers in diagnosis.AIM To elucidate the roles and diagnostic values ofα2-macroglobulin(α2-MG),podocalyxin(PCX),α-L-fucosidase(AFU),retinol-binding protein-4(RBP-4),and cystatin C(CysC)in DN.METHODS From December 2018 to December 2020,203 T2DM patients were enrolled in the study.Of these,115 were diagnosed with DN(115 patients),while the remaining 88 patients were classified as non-DN.The urinary levels ofα2-MG,PCX,and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility.RESULTS After adjustments for age and gender,significant positive correlations were observed between the biomarkers CysC,RBP-4,α2-MG/urinary creatinine(UCr),PCX/UCr,and AFU/UCr,and clinical indicators such as urinary albumin-to-creatinine ratio(UACR),serum creatinine,urea,24-h total urine protein,and neutrophil-to-lymphocyte ratio(NLR).Conversely,these biomarkers exhibited negative correlations with the estimated glomerular filtration rate(P<0.05).Receiver operating characteristic(ROC)curve analysis further demonstrated the diagnostic performance of these biomarkers,with UACR showcasing the highest area under the ROC curve(AUC^(ROC))at 0.97.CONCLUSION This study underscores the diagnostic significance ofα2-MG,PCX,and AFU in the development of DN.The biomarkers RBP-4,CysC,PCX,AFU,andα2-MG provide promising diagnostic insights,while UACR is the most potent diagnostic biomarker in assessing DN.展开更多
BACKGROUND： Previous experiments have confirmed bone morphogenetic proteins （BMPs） upregulate cholinergic expression in neurons isolated from the embryonic rat hippocampus and cerebral cortex. Therefore, BMPs could...BACKGROUND： Previous experiments have confirmed bone morphogenetic proteins （BMPs） upregulate cholinergic expression in neurons isolated from the embryonic rat hippocampus and cerebral cortex. Therefore, BMPs could be useful for treating Alzheimer＇s disease and other neurodegenerative diseases. OBJECTIVE： BMP-4 was infused into the hippocampal dentate gyrus of fomix-fimbria transected rats to test the effects of BMP-4 on cholinergic expression in dentate gyrus neurons, and to observe changes in spatial memory behavior. DESIGN： A randomized controlled animal experiment. SETTING： Department of Neurosurgery and Laboratory for Cell Biology, Institute of Geriatrics, General Hospital of Chinese PLA. MATERIALS： Twenty-seven healthy adult male Sprague Dawley （SD） rats, weighing 250-300 g, were provided by the Laboratory Animal Center of the General Hospital of Chinese PLA. Reagents： BMP-4 （B-2680, Sigma Company） and choline acetyl transferase （CHAT） antibody （AB5042, Chemicon Company） were used in this study. Equipments： a rat stereotaxic instrument （type： SN-2N, Narushige Group, Japan） and Image-prog-plus image analysis software （Media Cybernetics company, USA） were used in this study. The protocol was carried out in accordance with ethical guidelines for the use and care of animals. METHODS： This experiment was performed in the Institute of Geriatrics, General Hospital of Chinese PLA between July 2004 and March 2005. Rats were randomly divided into 4 groups： Alzheimer＇s disease group （n = 7）, normal control group （n = 5）, BMP-4-Alzheimer＇s disease group （n = 8）, and model group （n = 7）. In the Alzheimer＇s disease group, the left hippocampal fomix-fimbria of rats was transected to mimic Alzheimer＇s disease symptoms. In the BMP-4-Alzheimer＇s disease group, 1 μt L BMP-4 （10 mg/L） was perfused into the left dentate gyrus with a microinjector at 1 μ L/min. In the model group, 1 μ L saline was perfused into the same position by the same method. Twenty-eight days after injection, Morris water maze test was performed in all rats to test spatial memory. Time-to-platform and swim-path length were recorded. Immunohistochemical staining of cholinergic neurons was performed on brain sections containing dentate gyrus. The area covered by ChAT-positive cells was analyzed using an Image-prog-plus image analysis software. MAIN OUTCOME MEASURES： Area covered by ChAT-positive cells in the dentate gyrus. Time-to-platform and swim path-length. RESULTS： Twenty-seven rats were included in the final analysis. In the Alzheimer＇s disease group, the area covered by ChAT-positive cells was significantly smaller compared with the normal control group （F = 76.03, P 〈 0.01）. The area covered by ChAT-positive cells was significantly larger in the BMP-4- Alzheimer＇s disease group than in the model group （F = 35.17, P 〈 0.05）, but significantly smaller than in the normal control group （F = 40.17, P 〈 0.05）. Time-to-platform and swim-path length were significantly longer in the Alzheimer＇s disease group than in the normal control group （F =24.62 and 631.58, respectively, both P 〈 0.05）. Time-to-platform and swim-path length were significantly shorter in the BMP4-Alzheimer＇s disease group compared with the model group （F= 22.06 and 606.89, respectively P 〈 0.05）. CONCLUSION： Injection of BMP-4 into the dentate gyrus of Alzheimer＇s disease model rats alleviates central cholinergic system injury and concomitantly improves spatial memory.展开更多
Human embryonic stem cells (hESC) can be induced to differentiate to trophoblast by bone morphogenetic proteins (BMPs) and by aggregation to form embryoid bodies (EB), but there are many differences and controversies ...Human embryonic stem cells (hESC) can be induced to differentiate to trophoblast by bone morphogenetic proteins (BMPs) and by aggregation to form embryoid bodies (EB), but there are many differences and controversies regarding the nature of the differentiated cells. Our goals herein were to determine if BG02 cells form trophoblast-like cells (a) in the presence of BMP4-plus-basic fibroblast growth factor (FGF-2) and (b) upon EB formation, and (c) whether the BMP4 antagonist noggin elicits direct effects on gene expression and hormone production in the cells. Transcriptome profiling of hESC incubated with BMP4/FGF-2 showed a down-regulation of pluripotency-associated genes, an up-regulation of trophoblast-associated genes, and either a down-regulation or no change in gene expression for many markers of the three embryonic germ layers. Yet, there was up-regulation of several genes associated with mesoderm, ectoderm, and endoderm, strongly suggesting that differentiation to trophoblast-like cells under the conditions used does not yield a homogeneous cell type. Several genes, heretofore unreported, were identified that are altered in hESC in response to BMP4-mediated differentiation. The production of human chorionic gonadotropin (hCG), progesterone, and estradiol in the differentiated cells confirmed that trophoblast-like cells were obtained. Gene expression by EB was characterized by an up-regulation of a number of genes associated with trophoblast, ectoderm, endoderm, and mesoderm, and the production of hCG and progesterone confirmed that trophoblast-like cells were formed. These results suggest that, in the presence of FGF-2, BG02 cells respond to BMP4 to yield trophoblast-like cells, which are also obtained upon EB formation. Thus, BMP4-mediated differentiation of hESC represents a viable cell system for studying early developmental events post-implantation;however, up-regulation of non-trophoblast genes suggests a somewhat diverse response to BMP4/FGF-2. Noggin altered the transcription of a limited number of genes but, not surprisingly, did not lead to secretion of hormones.展开更多
本研究旨在探究线粒体复合物Ⅰ(ComplexⅠ,CⅠ)的核心结构蛋白NADH脱氢酶铁硫蛋白4(NADH Dehydrogenase(Ubiquinone)Fe S protein 4,NDUFS4)在涡虫成体干细胞功能维持与神经再生过程中的作用。通过克隆获得东亚三角涡虫(Dugesia sp.)ndu...本研究旨在探究线粒体复合物Ⅰ(ComplexⅠ,CⅠ)的核心结构蛋白NADH脱氢酶铁硫蛋白4(NADH Dehydrogenase(Ubiquinone)Fe S protein 4,NDUFS4)在涡虫成体干细胞功能维持与神经再生过程中的作用。通过克隆获得东亚三角涡虫(Dugesia sp.)ndufs4基因并进行序列及结构预测分析,结果显示其编码蛋白在保守结构域和关键氨基酸位点高度保守。采用RNA干扰技术持续敲降ndufs4表达,测定再生涡虫胚基(blastema)生长速率,并结合原位杂交与免疫组织化学等实验技术检测成体干细胞(Neoblasts)的增殖与分化、神经再生情况。结果表明,ndufs4敲降导致涡虫再生速率显著减慢,神经再生明显受损;同时,干细胞标记基因表达水平下降,干细胞分化进程受阻。上述结果说明,NDUFS4是维持涡虫成体干细胞群体功能及促进神经再生的必需蛋白,在生物再生中发挥重要调控功能。展开更多
骨质疏松症(osteoporosis,OP)是以骨密度降低、骨微结构异常为特征,脆性骨折风险显著增加的代谢性骨病。溴结构域蛋白4(bromodomain-containing protein 4,BRD4)是溴结构域蛋白(bromodomain and extra-terminal domain proteins,BET家族...骨质疏松症(osteoporosis,OP)是以骨密度降低、骨微结构异常为特征,脆性骨折风险显著增加的代谢性骨病。溴结构域蛋白4(bromodomain-containing protein 4,BRD4)是溴结构域蛋白(bromodomain and extra-terminal domain proteins,BET家族)的重要成员,属于表观遗传调控因子,在干细胞分化、细胞周期、炎症反应及癌症发生等过程中具有关键作用。近年来研究表明,BRD4在OP发病机制中扮演着重要角色。BRD4通过调控WNT4/NF-κB、Wnt/β-catenin和Runx2通路促进骨形成,同时经RANKL/NF-κB/MAPK信号抑制骨吸收,在OP进展中发挥双向调控作用。因此,BRD4可能成为治疗OP新靶点,为OP防治提供新导向。本文通过总结BRD4在OP中的作用机制,探讨BRD4在OP中的潜在作用靶点与可能治疗途径。未来研究应进一步探究BRD4与OP的具体作用机制,并开发新的治疗药物,以提高OP的临床治疗效果。展开更多
基金pported by the Natural Science Foundation of Inner Mongolia Autonomous Region,No.2022MS08057.
文摘BACKGROUND The intricate relationship between type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)presents a challenge in understanding the significance of various biomarkers in diagnosis.AIM To elucidate the roles and diagnostic values ofα2-macroglobulin(α2-MG),podocalyxin(PCX),α-L-fucosidase(AFU),retinol-binding protein-4(RBP-4),and cystatin C(CysC)in DN.METHODS From December 2018 to December 2020,203 T2DM patients were enrolled in the study.Of these,115 were diagnosed with DN(115 patients),while the remaining 88 patients were classified as non-DN.The urinary levels ofα2-MG,PCX,and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility.RESULTS After adjustments for age and gender,significant positive correlations were observed between the biomarkers CysC,RBP-4,α2-MG/urinary creatinine(UCr),PCX/UCr,and AFU/UCr,and clinical indicators such as urinary albumin-to-creatinine ratio(UACR),serum creatinine,urea,24-h total urine protein,and neutrophil-to-lymphocyte ratio(NLR).Conversely,these biomarkers exhibited negative correlations with the estimated glomerular filtration rate(P<0.05).Receiver operating characteristic(ROC)curve analysis further demonstrated the diagnostic performance of these biomarkers,with UACR showcasing the highest area under the ROC curve(AUC^(ROC))at 0.97.CONCLUSION This study underscores the diagnostic significance ofα2-MG,PCX,and AFU in the development of DN.The biomarkers RBP-4,CysC,PCX,AFU,andα2-MG provide promising diagnostic insights,while UACR is the most potent diagnostic biomarker in assessing DN.
文摘BACKGROUND： Previous experiments have confirmed bone morphogenetic proteins （BMPs） upregulate cholinergic expression in neurons isolated from the embryonic rat hippocampus and cerebral cortex. Therefore, BMPs could be useful for treating Alzheimer＇s disease and other neurodegenerative diseases. OBJECTIVE： BMP-4 was infused into the hippocampal dentate gyrus of fomix-fimbria transected rats to test the effects of BMP-4 on cholinergic expression in dentate gyrus neurons, and to observe changes in spatial memory behavior. DESIGN： A randomized controlled animal experiment. SETTING： Department of Neurosurgery and Laboratory for Cell Biology, Institute of Geriatrics, General Hospital of Chinese PLA. MATERIALS： Twenty-seven healthy adult male Sprague Dawley （SD） rats, weighing 250-300 g, were provided by the Laboratory Animal Center of the General Hospital of Chinese PLA. Reagents： BMP-4 （B-2680, Sigma Company） and choline acetyl transferase （CHAT） antibody （AB5042, Chemicon Company） were used in this study. Equipments： a rat stereotaxic instrument （type： SN-2N, Narushige Group, Japan） and Image-prog-plus image analysis software （Media Cybernetics company, USA） were used in this study. The protocol was carried out in accordance with ethical guidelines for the use and care of animals. METHODS： This experiment was performed in the Institute of Geriatrics, General Hospital of Chinese PLA between July 2004 and March 2005. Rats were randomly divided into 4 groups： Alzheimer＇s disease group （n = 7）, normal control group （n = 5）, BMP-4-Alzheimer＇s disease group （n = 8）, and model group （n = 7）. In the Alzheimer＇s disease group, the left hippocampal fomix-fimbria of rats was transected to mimic Alzheimer＇s disease symptoms. In the BMP-4-Alzheimer＇s disease group, 1 μt L BMP-4 （10 mg/L） was perfused into the left dentate gyrus with a microinjector at 1 μ L/min. In the model group, 1 μ L saline was perfused into the same position by the same method. Twenty-eight days after injection, Morris water maze test was performed in all rats to test spatial memory. Time-to-platform and swim-path length were recorded. Immunohistochemical staining of cholinergic neurons was performed on brain sections containing dentate gyrus. The area covered by ChAT-positive cells was analyzed using an Image-prog-plus image analysis software. MAIN OUTCOME MEASURES： Area covered by ChAT-positive cells in the dentate gyrus. Time-to-platform and swim path-length. RESULTS： Twenty-seven rats were included in the final analysis. In the Alzheimer＇s disease group, the area covered by ChAT-positive cells was significantly smaller compared with the normal control group （F = 76.03, P 〈 0.01）. The area covered by ChAT-positive cells was significantly larger in the BMP-4- Alzheimer＇s disease group than in the model group （F = 35.17, P 〈 0.05）, but significantly smaller than in the normal control group （F = 40.17, P 〈 0.05）. Time-to-platform and swim-path length were significantly longer in the Alzheimer＇s disease group than in the normal control group （F =24.62 and 631.58, respectively, both P 〈 0.05）. Time-to-platform and swim-path length were significantly shorter in the BMP4-Alzheimer＇s disease group compared with the model group （F= 22.06 and 606.89, respectively P 〈 0.05）. CONCLUSION： Injection of BMP-4 into the dentate gyrus of Alzheimer＇s disease model rats alleviates central cholinergic system injury and concomitantly improves spatial memory.
文摘Human embryonic stem cells (hESC) can be induced to differentiate to trophoblast by bone morphogenetic proteins (BMPs) and by aggregation to form embryoid bodies (EB), but there are many differences and controversies regarding the nature of the differentiated cells. Our goals herein were to determine if BG02 cells form trophoblast-like cells (a) in the presence of BMP4-plus-basic fibroblast growth factor (FGF-2) and (b) upon EB formation, and (c) whether the BMP4 antagonist noggin elicits direct effects on gene expression and hormone production in the cells. Transcriptome profiling of hESC incubated with BMP4/FGF-2 showed a down-regulation of pluripotency-associated genes, an up-regulation of trophoblast-associated genes, and either a down-regulation or no change in gene expression for many markers of the three embryonic germ layers. Yet, there was up-regulation of several genes associated with mesoderm, ectoderm, and endoderm, strongly suggesting that differentiation to trophoblast-like cells under the conditions used does not yield a homogeneous cell type. Several genes, heretofore unreported, were identified that are altered in hESC in response to BMP4-mediated differentiation. The production of human chorionic gonadotropin (hCG), progesterone, and estradiol in the differentiated cells confirmed that trophoblast-like cells were obtained. Gene expression by EB was characterized by an up-regulation of a number of genes associated with trophoblast, ectoderm, endoderm, and mesoderm, and the production of hCG and progesterone confirmed that trophoblast-like cells were formed. These results suggest that, in the presence of FGF-2, BG02 cells respond to BMP4 to yield trophoblast-like cells, which are also obtained upon EB formation. Thus, BMP4-mediated differentiation of hESC represents a viable cell system for studying early developmental events post-implantation;however, up-regulation of non-trophoblast genes suggests a somewhat diverse response to BMP4/FGF-2. Noggin altered the transcription of a limited number of genes but, not surprisingly, did not lead to secretion of hormones.
文摘本研究旨在探究线粒体复合物Ⅰ(ComplexⅠ,CⅠ)的核心结构蛋白NADH脱氢酶铁硫蛋白4(NADH Dehydrogenase(Ubiquinone)Fe S protein 4,NDUFS4)在涡虫成体干细胞功能维持与神经再生过程中的作用。通过克隆获得东亚三角涡虫(Dugesia sp.)ndufs4基因并进行序列及结构预测分析,结果显示其编码蛋白在保守结构域和关键氨基酸位点高度保守。采用RNA干扰技术持续敲降ndufs4表达,测定再生涡虫胚基(blastema)生长速率,并结合原位杂交与免疫组织化学等实验技术检测成体干细胞(Neoblasts)的增殖与分化、神经再生情况。结果表明,ndufs4敲降导致涡虫再生速率显著减慢,神经再生明显受损;同时,干细胞标记基因表达水平下降,干细胞分化进程受阻。上述结果说明,NDUFS4是维持涡虫成体干细胞群体功能及促进神经再生的必需蛋白,在生物再生中发挥重要调控功能。
文摘骨质疏松症(osteoporosis,OP)是以骨密度降低、骨微结构异常为特征,脆性骨折风险显著增加的代谢性骨病。溴结构域蛋白4(bromodomain-containing protein 4,BRD4)是溴结构域蛋白(bromodomain and extra-terminal domain proteins,BET家族)的重要成员,属于表观遗传调控因子,在干细胞分化、细胞周期、炎症反应及癌症发生等过程中具有关键作用。近年来研究表明,BRD4在OP发病机制中扮演着重要角色。BRD4通过调控WNT4/NF-κB、Wnt/β-catenin和Runx2通路促进骨形成,同时经RANKL/NF-κB/MAPK信号抑制骨吸收,在OP进展中发挥双向调控作用。因此,BRD4可能成为治疗OP新靶点,为OP防治提供新导向。本文通过总结BRD4在OP中的作用机制,探讨BRD4在OP中的潜在作用靶点与可能治疗途径。未来研究应进一步探究BRD4与OP的具体作用机制,并开发新的治疗药物,以提高OP的临床治疗效果。
