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
目的探讨免疫球蛋白A(IgA)肾病患者脂肪酸结合蛋白1(FABP1)和脂肪酸结合蛋白4(FABP4)水平与疾病活动性的相关性。方法选取2018年3月至2021年9月该院收治的IgA肾病患者240例作为观察组,另选取同期在该院体检健康的志愿者240例作为对照组...目的探讨免疫球蛋白A(IgA)肾病患者脂肪酸结合蛋白1(FABP1)和脂肪酸结合蛋白4(FABP4)水平与疾病活动性的相关性。方法选取2018年3月至2021年9月该院收治的IgA肾病患者240例作为观察组,另选取同期在该院体检健康的志愿者240例作为对照组。对比2组研究对象的收缩压、舒张压、24 h尿蛋白定量(24 h UTP)、肾小球滤过率(eGFR)和血肌酐(Scr)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、甘油三酯(TG)和血浆清蛋白(ALB)、FABP1、FABP4、IgA和补体C3(C3)水平。采用Pearson相关分析观察组血清FABP1、FABP4水平与IgA、C3、Scr、ALB和收缩压、舒张压、24 h UTP、eGFR、TC、TG、HDL-C的相关性;采用多因素Logistic回归分析影响IgA肾病患者疾病活动性的因素。结果观察组血清FABP4、IgA、C3、TC、TG和Scr水平以及收缩压、舒张压、24 h UTP显著高于对照组,而FABP1、eGFR、ALB和HDL-C水平显著低于对照组,差异均有统计学意义(P<0.05)。依据肾内活动性指数得分将观察组患者分为高分组(得分≥7分)174例和低分组(得分<7分)66例;与低分组相比,高分组血清FABP4、IgA和C3水平明显升高,FABP1、ALB水平和eGFR明显降低,差异均有统计学意义(P<0.05)。Pearson相关分析结果显示,IgA肾病患者血清FABP1水平均与IgA、C3、Scr水平及收缩压、舒张压、24 h UTP、TC和TG呈负相关(P<0.05),与eGFR、HDL-C和ALB水平呈正相关(P<0.05);血清FABP4水平均与IgA、C3、Scr水平和收缩压、舒张压、24 h UTP、TC和TG呈正相关(P<0.05),与eGFR、HDL-C和ALB水平呈负相关(P<0.05)。多因素Logistic回归分析结果显示,血清FABP4、IgA、C3水平升高是影响IgA肾病患者疾病活动性的危险因素(P<0.05),血清FABP1和ALB水平升高及eGFR增大是影响IgA肾病患者疾病活动性的保护因素(P<0.05)。结论IgA肾病患者血清FABP1水平降低,FABP4水平升高,二者与IgA肾病患者疾病活动性关系密切。展开更多
目的分析原发性高血压并发心力衰竭的独立危险因素,并探讨视黄醇结合蛋白4(retinol-binding protein 4,RBP4)丰度与心室重塑及心功能指标的相关性。方法选择2020年4月—2024年4月于安阳市人民医院就诊的104例原发性高血压合并心力衰竭...目的分析原发性高血压并发心力衰竭的独立危险因素,并探讨视黄醇结合蛋白4(retinol-binding protein 4,RBP4)丰度与心室重塑及心功能指标的相关性。方法选择2020年4月—2024年4月于安阳市人民医院就诊的104例原发性高血压合并心力衰竭患者纳入观察组,同时纳入52例原发性高血压未合并心力衰竭患者为对照组。比较两组患者一般数据、实验室指标、心功能指标及左室重塑指数。采用多因素logistic回归分析探讨原发性高血压并发心力衰竭的独立危险因素。依据美国纽约心脏病协会心功能分级将104例原发性高血压合并心力衰竭患者分Ⅱ级(n=39)、Ⅲ级(n=52)及Ⅳ级(n=13),分析RBP4丰度与心功能分级的关系。采用Pearson相关性分析探讨RBP4与心功能指标及左室重塑指数的相关性。结果多因素logistic回归分析显示,高血压病程、空腹血糖、总胆固醇、甘油三酯及RBP4丰度均为原发性高血压并发心力衰竭的危险因素(OR>1,P<0.05);左室重塑指数为原发性高血压并发心力衰竭的保护因素(0<OR<1,P<0.01)。单因素方差分析结果显示不同心功能分级患者血清RBP4丰度及左室重塑指数均存在显著差异(P<0.05)。且随着心功能分级的增加,血清RBP4丰度逐渐升高,左室重塑指数逐渐降低。Pearson相关性分析结果显示血清RBP4丰度与左心室舒张末期内径及右心室收缩末期内径呈正相关(P<0.05),与左心室射血分数及左室重塑指数呈负相关(P<0.05)。结论原发性高血压并发心力衰竭的独立影响因素包括高血压病程、空腹血糖、总胆固醇、甘油三酯、左室重塑指数及RBP4丰度。血清高丰度的RBP4与心功能恶化及左室重塑密切相关。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.
文摘目的探讨免疫球蛋白A(IgA)肾病患者脂肪酸结合蛋白1(FABP1)和脂肪酸结合蛋白4(FABP4)水平与疾病活动性的相关性。方法选取2018年3月至2021年9月该院收治的IgA肾病患者240例作为观察组,另选取同期在该院体检健康的志愿者240例作为对照组。对比2组研究对象的收缩压、舒张压、24 h尿蛋白定量(24 h UTP)、肾小球滤过率(eGFR)和血肌酐(Scr)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、甘油三酯(TG)和血浆清蛋白(ALB)、FABP1、FABP4、IgA和补体C3(C3)水平。采用Pearson相关分析观察组血清FABP1、FABP4水平与IgA、C3、Scr、ALB和收缩压、舒张压、24 h UTP、eGFR、TC、TG、HDL-C的相关性;采用多因素Logistic回归分析影响IgA肾病患者疾病活动性的因素。结果观察组血清FABP4、IgA、C3、TC、TG和Scr水平以及收缩压、舒张压、24 h UTP显著高于对照组,而FABP1、eGFR、ALB和HDL-C水平显著低于对照组,差异均有统计学意义(P<0.05)。依据肾内活动性指数得分将观察组患者分为高分组(得分≥7分)174例和低分组(得分<7分)66例;与低分组相比,高分组血清FABP4、IgA和C3水平明显升高,FABP1、ALB水平和eGFR明显降低,差异均有统计学意义(P<0.05)。Pearson相关分析结果显示,IgA肾病患者血清FABP1水平均与IgA、C3、Scr水平及收缩压、舒张压、24 h UTP、TC和TG呈负相关(P<0.05),与eGFR、HDL-C和ALB水平呈正相关(P<0.05);血清FABP4水平均与IgA、C3、Scr水平和收缩压、舒张压、24 h UTP、TC和TG呈正相关(P<0.05),与eGFR、HDL-C和ALB水平呈负相关(P<0.05)。多因素Logistic回归分析结果显示,血清FABP4、IgA、C3水平升高是影响IgA肾病患者疾病活动性的危险因素(P<0.05),血清FABP1和ALB水平升高及eGFR增大是影响IgA肾病患者疾病活动性的保护因素(P<0.05)。结论IgA肾病患者血清FABP1水平降低,FABP4水平升高,二者与IgA肾病患者疾病活动性关系密切。
文摘目的分析原发性高血压并发心力衰竭的独立危险因素,并探讨视黄醇结合蛋白4(retinol-binding protein 4,RBP4)丰度与心室重塑及心功能指标的相关性。方法选择2020年4月—2024年4月于安阳市人民医院就诊的104例原发性高血压合并心力衰竭患者纳入观察组,同时纳入52例原发性高血压未合并心力衰竭患者为对照组。比较两组患者一般数据、实验室指标、心功能指标及左室重塑指数。采用多因素logistic回归分析探讨原发性高血压并发心力衰竭的独立危险因素。依据美国纽约心脏病协会心功能分级将104例原发性高血压合并心力衰竭患者分Ⅱ级(n=39)、Ⅲ级(n=52)及Ⅳ级(n=13),分析RBP4丰度与心功能分级的关系。采用Pearson相关性分析探讨RBP4与心功能指标及左室重塑指数的相关性。结果多因素logistic回归分析显示,高血压病程、空腹血糖、总胆固醇、甘油三酯及RBP4丰度均为原发性高血压并发心力衰竭的危险因素(OR>1,P<0.05);左室重塑指数为原发性高血压并发心力衰竭的保护因素(0<OR<1,P<0.01)。单因素方差分析结果显示不同心功能分级患者血清RBP4丰度及左室重塑指数均存在显著差异(P<0.05)。且随着心功能分级的增加,血清RBP4丰度逐渐升高,左室重塑指数逐渐降低。Pearson相关性分析结果显示血清RBP4丰度与左心室舒张末期内径及右心室收缩末期内径呈正相关(P<0.05),与左心室射血分数及左室重塑指数呈负相关(P<0.05)。结论原发性高血压并发心力衰竭的独立影响因素包括高血压病程、空腹血糖、总胆固醇、甘油三酯、左室重塑指数及RBP4丰度。血清高丰度的RBP4与心功能恶化及左室重塑密切相关。
