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Specific Alterations of Gut Microbiota in Chinese Patients with Hypertension: A Systematic Review and Meta-Analysis 中国高血压患者肠道微生物群的特异性改变:一项系统回顾和荟萃分析
Pub Date : 2022-04-08 DOI: 10.1159/000524282
Yunlong Qin, Jin Zhao, Yuwei Wang, M. Bai, Shiren Sun
Background: China has the largest absolute burden of hypertension (HTN) in the world. Gut dysbiosis may be a potentially modifiable risk factor for HTN. However, the characteristics of gut microbiota in Chinese populations with HTN remain to be determined. Methods: We systematically searched for studies comparing the gut microbial in HTN with healthy controls in databases. The cut-off date was December 30, 2021. Semiquantitative analysis and meta-analysis with standardized mean differences of the alteration in gut microbiota were carried out. Results: A total of 16 studies involving 2,372 patients with HTN and 849 controls were included, covering 16 Chinese provinces or regions. The present study supports that compared to healthy population, the diversity of patients with HTN is significantly compromised, while richness is overall preserved. To be specific, a significant increase of the Firmicutes (F)/Bacteroidetes (B) ratio is considered as a special parameter of gut microbiota in HTN patients. The increased abundance of phylum Firmicutes, genus Megasphaera, Escherichia_Shigella, and Klebsiella while the lower abundance of phylum Bacteroidetes, genus Bifidobacterium, Faecalibacterium, Roseburia, and Ruminococcus may be associated with HTN. The gut microbial metabolism in HTN was more abundant in lipopolysaccharide biosynthesis, membrane transport, and steroid degradation. Conclusions: Variation in gut microbial parameters is likely associated with Chinese patients with HTN. Further investigations should distinguish geographical and ethnic characteristics to develop in-depth knowledge of the underlying mechanisms by which gut dysbiosis contributes to HTN.
背景:中国是世界上高血压(HTN)绝对负担最大的国家。肠道生态失调可能是HTN的一个潜在可改变的危险因素。然而,中国HTN人群的肠道菌群特征仍有待确定。方法:我们系统地检索了数据库中HTN与健康对照者肠道微生物比较的研究。截止日期为2021年12月30日。对肠道菌群改变的标准化平均差异进行半定量分析和荟萃分析。结果:共纳入16项研究,涉及2372例HTN患者和849例对照,覆盖中国16个省或地区。本研究支持,与健康人群相比,HTN患者的多样性显著降低,而丰富度总体上保持不变。具体而言,厚壁菌门(F)/拟杆菌门(B)比值的显著升高被认为是HTN患者肠道微生物群的一个特殊参数。厚壁菌门、巨生菌属、志贺氏杆菌属和克雷伯氏菌的丰度增加,而拟杆菌门、双歧杆菌属、粪杆菌属、玫瑰菌属和鲁米诺球菌的丰度降低可能与HTN有关。HTN的肠道微生物代谢在脂多糖生物合成、膜转运和类固醇降解方面更为丰富。结论:肠道微生物参数的变化可能与中国HTN患者有关。进一步的调查应区分地理和种族特征,以深入了解肠道生态失调导致HTN的潜在机制。
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引用次数: 5
Intravascular Renal Denervation Reduces Ambulatory and Office Blood Pressure in Patients with Essential Hypertension: A Meta-Analysis of Randomized Sham-Controlled Trials 血管内肾去神经可降低原发性高血压患者的门诊和办公室血压:一项随机假对照试验的荟萃分析
Pub Date : 2022-04-06 DOI: 10.1159/000524171
Xiaoxv Yang, Hui Liu, Shifan Chen, P. Dong, Di Zhao
Background: This meta-analysis was designed to evaluate the antihypertensive efficacy of intravascular renal denervation (RDN) in patients with essential hypertension, especially to determine the magnitude of blood pressure (BP) reduction with RDN therapy using second-generation catheters. Methods: PubMed was searched to identify randomized sham-controlled trials from inception through August 2021. The endpoints were changes in 24-h ambulatory BP or office BP. This meta-analysis was performed by calculating the weighted mean difference (WMD) with 95% confidence interval (CI) using the random-effects model when the I2 index was <50%. A fixed-effects model was used when the I2 index was ≥50%. Results: A total of 1,297 patients were included in 8 randomized, sham-controlled trials in this meta-analysis. Intravascular RDN reduced 24-h ambulatory systolic BP (SBP) −3.02 (WMD, 95% CI: −4.95, −1.10, p < 0.01) and diastolic BP (DBP) −1.66 (WMD, 95% CI: −2.44, −0.88, p < 0.001) mm Hg, respectively. In the studies using first-generation catheters, the WMDs of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham control were −2.67 (95% CI: −5.08, −0.27; p < 0.05; I2 = 0%, p = 0.53) and −0.82 (95% CI: −2.19, 0.56; p > 0.05; I2 = 0%, p = 0.64) mm Hg. In the studies using second-generation catheters, the WMDs of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham control were −3.14 (95% CI: −5.94, −0.33, p < 0.05; I2 = 71%, p = 0.008) and −2.06 (95% CI: −3.02, −1.11, p < 0.001; I2 = 50%, p = 0.09) mm Hg. Intravascular RDN using second-generation catheters reduced office SBP −6.30 (WMD, 95% CI: −7.67, −4.93, p < 0.001; I2 = 43%, p = 0.14) and DBP −3.88 (WMD, 95% CI: −4.44, −3.33, p < 0.001; I2 = 42%, p = 0.14) mm Hg, respectively. Conclusions: Intravascular RDN using second-generation catheters reduces ambulatory and office BP in patients with essential hypertension. The selection of appropriate hypertensive patients may be the major challenge for the performance of intravascular RDN in routine clinical practice.
背景:本荟萃分析旨在评估原发性高血压患者血管内肾去神经支配(RDN)的降压效果,特别是确定使用第二代导管进行RDN治疗的血压(BP)降低幅度。方法:检索PubMed以确定从开始到2021年8月的随机假对照试验。终点是24小时动态血压或办公室血压的变化。当I2指数为0.05时,采用随机效应模型计算95%置信区间(CI)的加权平均差(WMD)进行meta分析;I2 = 0%, p = 0.64) mm Hg。在使用第二代导管的研究中,血管内RDN和假对照组24小时动态收缩压和舒张压变化的wmd为- 3.14 (95% CI: - 5.94, - 0.33, p < 0.05;I2 = 71%, p = 0.008)和−2.06(95%置信区间CI: 3.02−−1.11,p < 0.001;I2 = 50%, p = 0.09) mm Hg。血管内RDN使用第二代导管降低办公室收缩压- 6.30 (WMD, 95% CI: - 7.67, - 4.93, p < 0.001;I2 = 43%, p = 0.14)和DBP - 3.88 (WMD, 95% CI: - 4.44, - 3.33, p < 0.001;I2 = 42%, p = 0.14) mm Hg。结论:血管内RDN使用第二代导管可降低原发性高血压患者的动态血压和办公室血压。选择合适的高血压患者可能是常规临床实践中血管内RDN性能的主要挑战。
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引用次数: 2
The Dopamine System: Insights between Kidney and Brain 多巴胺系统:肾脏和大脑之间的洞察
Pub Date : 2022-04-04 DOI: 10.1159/000522132
Antonio de Donato, V. Buonincontri, Gianmarco Borriello, Giuseppe Martinelli, P. Mone
Background: Chronic kidney disease (CKD) is one of the most common diseases in adult age, and it is typical of older adults. Recent data suggest that almost half of the elders have CKD. It is now clear that CKD is accompanied, in the early stages, by cognitive impairment, together with depression and subtle abnormalities in motor control (such as gait and balance alterations). Summary: Several data suggest a link between brain dopamine and kidney diseases. Metabolic syndrome and diabetes can affect dopamine neuron survival (leading to Parkinson’s disease). Several uremic toxins in CKD (uric acid, indoxyl sulfate) and trace elements accumulating in CKD (aluminum, manganese) can also modify the dopaminergic system. Hormones produced by the kidney such as vitamin D are neuroprotective for dopamine neurons. Dopaminergic drugs are useful for the treatment of a common sleep disorder in CKD, the restless legs syndrome. However, experiments on animal models of CKD show conflicting results regarding a modification of dopamine neurons. Key Messages: Several observations suggest a limited relevance of the dopaminergic system in CKD-related cognitive impairment. However, a common sleep disturbance in CKD, the restless legs syndrome, improves with dopaminergic drugs. Therefore, it remains to be established the role of the dopamine system in subtle motor dysfunction observed in CKD, such as tremors, gait alterations, and central sleep apnea.
背景:慢性肾脏疾病(CKD)是成年人最常见的疾病之一,以老年人为典型。最近的数据显示,几乎一半的老年人患有慢性肾病。现在很清楚,CKD在早期阶段伴有认知障碍、抑郁和运动控制的细微异常(如步态和平衡改变)。总结:一些数据表明脑多巴胺和肾脏疾病之间存在联系。代谢综合征和糖尿病会影响多巴胺神经元的存活(导致帕金森病)。CKD中的一些尿毒症毒素(尿酸、硫酸吲哚酚)和在CKD中积累的微量元素(铝、锰)也可以改变多巴胺能系统。肾脏产生的激素,如维生素D,对多巴胺神经元具有神经保护作用。多巴胺能药物对慢性肾病中一种常见的睡眠障碍——不宁腿综合症——的治疗很有用。然而,在CKD动物模型上的实验显示了多巴胺神经元修饰的矛盾结果。关键信息:一些观察结果表明,多巴胺能系统在ckd相关认知障碍中的相关性有限。然而,慢性肾病中一种常见的睡眠障碍,不宁腿综合征,可以通过多巴胺能药物得到改善。因此,多巴胺系统在CKD中观察到的细微运动功能障碍(如震颤、步态改变和中枢性睡眠呼吸暂停)中的作用仍有待确定。
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引用次数: 6
Requirement of Na+/H+ Exchanger NHE1 for Vasopressin-Induced Osteogenic Signaling and Calcification in Human Aortic Smooth Muscle Cells Na+/H+交换物NHE1对加压素诱导的人主动脉平滑肌细胞成骨信号和钙化的需求
Pub Date : 2022-03-25 DOI: 10.1159/000524050
Xuexue Zhu, Ke Ma, Kuo Zhou, X-D Pan, Jibin Liu, B. Nürnberg, I. Alesutan, J. Völkl, F. Lang
Background/Aims: Vasopressin is a powerful stimulator of vascular calcification, augmenting osteogenic signaling in vascular smooth muscle cells (VSMCs) including upregulation of transcription factors such as core-binding factor α-1 (CBFA1), msh homeobox 2 (MSX2), and SRY-Box 9 (SOX9), as well as of tissue-nonspecific alkaline phosphatase (ALPL). Vasopressin-induced osteogenic signaling and calcification require the serum- and glucocorticoid-inducible kinase 1 (SGK1). Known effects of SGK1 include upregulation of Na+/H+ exchanger 1 (NHE1). NHE1 further participates in the regulation of reactive oxygen species (ROS). NHE1 has been shown to participate in the orchestration of bone mineralization. The present study, thus, explored whether vasopressin modifies NHE1 expression and ROS generation, as well as whether pharmacological inhibition of NHE1 disrupts vasopressin-induced osteogenic signaling and calcification in VSMCs. Methods: Human aortic smooth muscle cells (HAoSMCs) were treated with vasopressin in the absence or presence of SGK1 silencing, SGK1 inhibitor GSK-650394, and NHE1 blocker cariporide. Transcript levels were determined by using quantitative real-time polymerase chain reaction, protein abundance by Western blotting, ROS generation with 2′,7′-dichlorofluorescein diacetate fluorescence, and ALP activity and calcium content by using colorimetric assays. Results: Vasopressin significantly enhanced the NHE1 transcript and protein levels in HAoSMCs, effects significantly blunted by SGK1 inhibition with GSK-650394 or SGK1 silencing. Vasopressin increased ROS accumulation, an effect significantly blocked by the NHE1 inhibitor cariporide. Vasopressin further significantly increased osteogenic markers CBFA1, MSX2, SOX9, and ALPL transcript levels, as well as ALP activity and calcium content in HAoSMCs, all effects significantly blunted by SGK1 silencing or in the presence of GSK-650394 or cariporide. Conclusion: Vasopressin stimulates NHE1 expression and ROS generation, an effect dependent on SGK1 and required for vasopressin-induced stimulation of osteogenic signaling and calcification of VSMCs.
背景/目的:血管加压素是一种强大的血管钙化刺激剂,增强血管平滑肌细胞(VSMCs)的成骨信号,包括上调核心结合因子α-1 (CBFA1)、msh同源盒2 (MSX2)和sly - box 9 (SOX9)等转录因子,以及组织非特异性碱性磷酸酶(ALPL)。抗利尿激素诱导的成骨信号和钙化需要血清和糖皮质激素诱导的激酶1 (SGK1)。已知SGK1的作用包括Na+/H+交换器1 (NHE1)的上调。NHE1进一步参与活性氧(ROS)的调控。NHE1已被证明参与骨矿化的编排。因此,本研究探讨了抗利尿激素是否会改变NHE1的表达和ROS的产生,以及NHE1的药理抑制是否会破坏抗利尿激素诱导的vsmc的成骨信号和钙化。方法:在没有或存在SGK1沉默、SGK1抑制剂GSK-650394和NHE1阻滞剂cariporide的情况下,用加压素处理人主动脉平滑肌细胞(HAoSMCs)。转录产物水平采用实时定量聚合酶链反应测定,蛋白丰度采用Western blotting测定,ROS生成采用2′,7′-二氯荧光素双醋酸酯荧光法测定,ALP活性和钙含量采用比色法测定。结果:加压素显著提高了HAoSMCs中NHE1转录物和蛋白水平,而用GSK-650394或SGK1沉默抑制SGK1则显著减弱了这一作用。抗利尿激素增加ROS积累,这一作用被NHE1抑制剂cariporide显著阻断。加压素进一步显著提高了成骨标志物CBFA1、MSX2、SOX9和ALPL转录物水平,以及HAoSMCs中ALP活性和钙含量,所有这些作用都被SGK1沉默或GSK-650394或cariporide存在显著减弱。结论:抗利尿激素刺激NHE1表达和ROS生成,这一作用依赖于SGK1,是抗利尿激素诱导的成骨信号和VSMCs钙化的刺激所必需的。
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引用次数: 3
An Integrative in silico Study to Discover Key Drivers in Pathogenicity of Focal and Segmental Glomerulosclerosis 一项综合计算机研究发现局灶性和节段性肾小球硬化致病性的关键驱动因素
Pub Date : 2022-03-18 DOI: 10.1159/000524133
A. Gholaminejad, Maryam Ghaeidamini, J. Simal-Gándara, A. Roointan
Background: Focal and segmental glomerulosclerosis (FSGS) is a clinical-pathologic condition marked by segmental and localized glomerular damages. Despite investigations, the molecular mechanisms behind FSGS development remain to be more clarified. By a comprehensive analysis of an FSGS-related array set, the aim of this study was to unravel the top pathways and molecules involved in the pathogenesis of this disorder. Methods: FSGS-related microarray dataset (GSE129973) from the Gene Expression Omnibus database was quality checked, analyzed, and its differentially expressed genes (DEGs) (log2 fold change > 1) were used for the construction of a protein-protein interaction (PPI) network (STRING). The degree of centrality was considered to select the hub molecules in the network. The weighted gene co-expression network analysis (WGCNA) was utilized to construct co-expression modules. Hub molecules were selected based on module membership and gene significance values in the disease’s most correlated module. After spotting the key molecules considering both strategies, their expression pattern was checked in other FSGS microarray datasets. Gene ontology and Reactome pathway enrichment analyses were performed on the DEGs of the related module. Results: After quality checking, normalization, and analysis of the dataset, 5,296 significant DEGs, including 2,469 upregulated and 2,827 downregulated DEGs were identified. The WGCNA algorithm clustered the DEGs into nine independent co-expression modules. The disease most correlated module (black module) was recognized and considered for further enrichment analysis. The immune system, cell cycle, and vesicle-mediated transports were among the top enriched terms for the identified module’s DEGs. The immune system, cell cycle, and vesicle-mediated transports were among the top enriched terms for the black module’s DEGs. The key molecules (BMP-2 and COL4A1) were identified as common hub molecules extracted from the two methods of PPI and the co-expressed networks. The two identified key molecules were validated in other FSGS datasets, where a similar pattern of expression was observed for both the genes. Conclusions: Two hub molecules (BMP-2 and COL4A) and some pathways (vesicle-mediated transport) were recognized as potential players in the pathogenesis of FSGS.
背景:局灶性和节段性肾小球硬化(FSGS)是一种以节段性和局域性肾小球损伤为特征的临床病理状态。尽管进行了研究,但FSGS发展背后的分子机制仍有待进一步阐明。通过对fsgs相关阵列的综合分析,本研究的目的是揭示参与该疾病发病机制的主要途径和分子。方法:对基因表达Omnibus数据库中fsgs相关微阵列数据集(GSE129973)进行质量检查和分析,并利用其差异表达基因(DEGs) (log2倍变化> 1)构建蛋白-蛋白相互作用(PPI)网络(STRING)。通过考虑中心度来选择网络中的枢纽分子。采用加权基因共表达网络分析(WGCNA)构建共表达模块。根据疾病最相关模块的模块隶属度和基因显著性值选择枢纽分子。在确定了考虑这两种策略的关键分子后,在其他FSGS微阵列数据集中检查它们的表达模式。对相关模块的deg进行基因本体和Reactome通路富集分析。结果:经过对数据集的质量检查、归一化和分析,鉴定出5296个显著的deg,其中包括2469个上调deg和2827个下调deg。WGCNA算法将deg聚类为9个独立的共表达模块。识别出疾病最相关模块(黑色模块),并考虑进一步富集分析。免疫系统、细胞周期和囊泡介导的运输是被鉴定模块的deg的最丰富的术语。免疫系统、细胞周期和囊泡介导的运输是黑色模组的deg中最丰富的术语。关键分子(BMP-2和COL4A1)被鉴定为从PPI和共表达网络两种方法中提取的共同枢纽分子。这两个鉴定的关键分子在其他FSGS数据集中得到了验证,在这些数据集中观察到两个基因的相似表达模式。结论:两个中心分子(BMP-2和COL4A)和一些途径(囊泡介导的运输)被认为是FSGS发病机制的潜在参与者。
{"title":"An Integrative in silico Study to Discover Key Drivers in Pathogenicity of Focal and Segmental Glomerulosclerosis","authors":"A. Gholaminejad, Maryam Ghaeidamini, J. Simal-Gándara, A. Roointan","doi":"10.1159/000524133","DOIUrl":"https://doi.org/10.1159/000524133","url":null,"abstract":"Background: Focal and segmental glomerulosclerosis (FSGS) is a clinical-pathologic condition marked by segmental and localized glomerular damages. Despite investigations, the molecular mechanisms behind FSGS development remain to be more clarified. By a comprehensive analysis of an FSGS-related array set, the aim of this study was to unravel the top pathways and molecules involved in the pathogenesis of this disorder. Methods: FSGS-related microarray dataset (GSE129973) from the Gene Expression Omnibus database was quality checked, analyzed, and its differentially expressed genes (DEGs) (log2 fold change > 1) were used for the construction of a protein-protein interaction (PPI) network (STRING). The degree of centrality was considered to select the hub molecules in the network. The weighted gene co-expression network analysis (WGCNA) was utilized to construct co-expression modules. Hub molecules were selected based on module membership and gene significance values in the disease’s most correlated module. After spotting the key molecules considering both strategies, their expression pattern was checked in other FSGS microarray datasets. Gene ontology and Reactome pathway enrichment analyses were performed on the DEGs of the related module. Results: After quality checking, normalization, and analysis of the dataset, 5,296 significant DEGs, including 2,469 upregulated and 2,827 downregulated DEGs were identified. The WGCNA algorithm clustered the DEGs into nine independent co-expression modules. The disease most correlated module (black module) was recognized and considered for further enrichment analysis. The immune system, cell cycle, and vesicle-mediated transports were among the top enriched terms for the identified module’s DEGs. The immune system, cell cycle, and vesicle-mediated transports were among the top enriched terms for the black module’s DEGs. The key molecules (BMP-2 and COL4A1) were identified as common hub molecules extracted from the two methods of PPI and the co-expressed networks. The two identified key molecules were validated in other FSGS datasets, where a similar pattern of expression was observed for both the genes. Conclusions: Two hub molecules (BMP-2 and COL4A) and some pathways (vesicle-mediated transport) were recognized as potential players in the pathogenesis of FSGS.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73883755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Correlation between Tubulointerstitial Lesion and Blood Pressure in Lupus Nephritis Patients: A Pathological, Retrospective Study 狼疮性肾炎患者肾小管间质病变与血压的相关性:一项病理回顾性研究
Pub Date : 2022-03-08 DOI: 10.1159/000523793
Ruili Yuan, Y. Zhong, Yan Zeng, Jing Zhang
Objective: The objective was to study the influence of pathological factors of glomerular lesion (GL), tubulointerstitial lesion (TIL), and arteriosclerotic lesion on the blood pressure (BP) of lupus nephritis (LN). Methods: The pathological data and clinical characteristics of 69 LN patients who underwent their first renal biopsy in Chengdu Second People’s Hospital from 2012 to 2018 were retrospectively analyzed. The revised 2018 ISN/RPS classification criteria of LN were used to assess the GL and TIL. The lesion index of interlobar/arcuate artery and arteriolar was calculated. Multiple linear regressions were used to analyze the effects of GL, TIL, and vascular lesion (VL) on estimated glomerular filtration rate, systolic BP (SBP), and proteinuria. Results: TIL and VL scores were different between the various grades of BP (p = 0.009, 0.019). After adjusting for gender and age, multiple linear regression showed that only TIL was linearly correlated with SBP (p = 0.022). Conclusion: After adjusting for gender and age, TIL is related to SBP and has a linear relationship with them.
目的:探讨肾小球病变(GL)、小管间质病变(TIL)和动脉硬化病变病理因素对狼疮性肾炎(LN)患者血压(BP)的影响。方法:回顾性分析2012 ~ 2018年成都市第二人民医院69例LN患者首次肾活检的病理资料及临床特点。采用经修订的2018年ISN/RPS LN分类标准评估GL和TIL。计算叶间动脉/弓状动脉及小动脉病变指数。采用多元线性回归分析GL、TIL和血管病变(VL)对肾小球滤过率、收缩压(SBP)和蛋白尿的影响。结果:不同程度BP患者的TIL和VL评分差异有统计学意义(p = 0.009, 0.019)。在调整性别和年龄后,多元线性回归显示只有TIL与收缩压呈线性相关(p = 0.022)。结论:经性别、年龄调整后,TIL与收缩压相关,两者呈线性关系。
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引用次数: 0
Circ_0037866 Contributes to the Tumorigenesis of Renal Cell Carcinoma by Sequestering miR-384 to Elevate Chromobox 5 Expression Circ_0037866通过分离miR-384提高Chromobox 5表达参与肾细胞癌的发生
Pub Date : 2022-03-04 DOI: 10.1159/000522190
Xiaoqiang Shi, Shichao Song, Ying Gao, Zhenyu Cui, Wentao Wang, Mingkai Liu
Background: Circular RNAs (circRNAs) were demonstrated to have roles in the carcinogenesis of renal cell carcinoma (RCC). Hence, this work aimed to determine the functions and molecular mechanism of circ_0037866 in regulating the progression of RCC. Methods: Quantitative real-time polymerase chain reaction and Western blotting were used to detect the levels of genes and proteins. In vitro assays, including colony formation, 5-ethynyl-2′-deoxyuridine, flow cytometry, transwell assays, and in vivo tumor formation, were conducted to investigate the effects of circ_0037866 on RCC tumorigenesis. Dual-luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation assay were used to confirm the interaction between miR-384 and circ_0037866 or Chromobox 5 (CBX5). Results: Circ_0037866 is a stable circRNA and was found to be increased in RCC tissues and cells. Functionally, circ_0037866 silencing suppressed RCC cell survival, invasion, and migration in vitro, and impeded RCC cell tumorigenesis in the subcutaneous xenograft model. Mechanistically, circ_0037866 could function as a sponge for miR-384 to elevate the expression of its target CBX5. Furthermore, a series of rescue experiments showed that miR-384 inhibition reversed the anticancer effects of circ_0037866 knockdown on RCC cells; besides that, miR-384 restoration suppressed RCC cell growth and mobility, which were attenuated by CBX5 overexpression. Conclusion: Circ_0037866 knockdown restrains the tumorigenesis of RCC by miR-384/CBX5, revealing a promising molecular target for RCC therapy.
背景:环状rna (circRNAs)已被证明在肾细胞癌(RCC)的癌变过程中发挥作用。因此,本研究旨在确定circ_0037866在调控RCC进展中的功能和分子机制。方法:采用实时定量聚合酶链反应和Western blotting检测基因和蛋白水平。体外实验包括集落形成、5-乙基-2 ' -脱氧尿苷、流式细胞术、transwell实验和体内肿瘤形成,研究circ_0037866对RCC肿瘤发生的影响。采用双荧光素酶报告基因法、RNA下拉法和RNA免疫沉淀法确认miR-384与circ_0037866或Chromobox 5 (CBX5)之间的相互作用。结果:Circ_0037866是一个稳定的circRNA,在RCC组织和细胞中被发现增加。在功能上,circ_0037866沉默抑制了RCC细胞的体外存活、侵袭和迁移,并在皮下异种移植模型中阻碍了RCC细胞的肿瘤发生。在机制上,circ_0037866可以作为miR-384的海绵,提高其靶CBX5的表达。此外,一系列挽救性实验表明,miR-384抑制逆转了circ_0037866敲低对RCC细胞的抗癌作用;此外,miR-384的恢复抑制了RCC细胞的生长和移动性,CBX5过表达减弱了这种抑制作用。结论:Circ_0037866敲低可通过miR-384/CBX5抑制RCC的肿瘤发生,为RCC治疗提供了一个有前景的分子靶点。
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引用次数: 1
Acknowledgement to the Reviewers 向审稿人致谢
Pub Date : 2021-12-01 DOI: 10.1159/000520308
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引用次数: 0
Cystatin C in Evaluating Renal Function in Ureteral Calculi Hydronephrosis in Adults 胱氨酸抑素C评价成人输尿管结石性肾积水患者肾功能
Pub Date : 2019-12-04 DOI: 10.1159/000504441
W. Mao, Shenghua Liu, Keyi Wang, Miao Wang, Heng Shi, Qunlong Liu, Meiyu Bao, Bo Peng, J. Geng
Background: Serum cystatin C (CysC) is still becoming used as a marker of renal function but is far from being commonly used worldwide. The purpose of this study was to characterize the ureteral calculi patients with hydronephrosis-caused CysC changes in renal function. Methods: To better reflect the changes of renal function, we constructed models of ureteral obstruction in rats to mimic the hydronephrosis caused by human ureteral calculi. Moreover, our study included 200 patients diagnosed with ureteral calculi in our hospital between June 2017 and 2018. We compared the estimated glomerular filtration rate using different equations based on CysC and/or serum creatinine (SCr). Results: We found that the expression of CysC and SCr increased with the prolonged obstruction time by enzyme linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry further demonstrated that the expression of CysC increases with the degree of hydronephrosis. Among 200 patients with ureteral calculi, 40 (20.0%) had no hydronephrosis, 110 (55.0%) had mild hydronephrosis, 32 (16.0%) had moderate hydronephrosis and 18 (9.0%) had severe hydronephrosis. As the degree of hydronephrosis increased, the expression of neutrophil percentage, CysC, blood urea nitrogen, SCr and serum uric acid also increased. Multivariate analyses demonstrated that only CysC was an independent risk factor for hydronephrosis (p = 0.003). In addition, CysC and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) CysC equation showed the highest veracity in renal function estimation of patients with hydronephrosis caused by ureteral calculus. Conclusion: For patients with hydronephrosis caused by ureteral calculi, CysC better reflects the changes in renal function, and the CKD-EPI CysC equation has the highest accuracy.
背景:血清胱抑素C (CysC)仍被用作肾功能的标志物,但远未在世界范围内普遍使用。本研究的目的是探讨输尿管结石合并肾积水引起的CysC肾功能改变的特点。方法:为了更好地反映肾脏功能的变化,我们建立大鼠输尿管梗阻模型,模拟人类输尿管结石引起的肾积水。此外,我们的研究纳入了2017年6月至2018年6月在我院诊断为输尿管结石的200例患者。我们使用基于CysC和/或血清肌酐(SCr)的不同方程来比较估计的肾小球滤过率。结果:酶联免疫吸附法发现CysC和SCr的表达随阻塞时间的延长而增加。定量实时聚合酶链反应、Western blot和免疫组织化学进一步证实CysC的表达随肾积水程度的增加而增加。200例输尿管结石患者中,无肾积水40例(20.0%),轻度肾积水110例(55.0%),中度肾积水32例(16.0%),重度肾积水18例(9.0%)。随着肾积水程度的增加,中性粒细胞百分比、CysC、血尿素氮、SCr、血清尿酸的表达也增加。多因素分析表明,只有CysC是肾积水的独立危险因素(p = 0.003)。此外,CysC和慢性肾脏病流行病学合作组织(CKD-EPI)的CysC方程对输尿管结石所致肾积水患者的肾功能估计准确性最高。结论:对于输尿管结石所致肾积水患者,CysC更能反映肾功能的变化,CKD-EPI CysC方程准确性最高。
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引用次数: 16
True Arterial Stiffness Does Not Change between Dialysis Sessions during 1 Week in Outpatients on Intermitted Hemodialysis 门诊间断血液透析患者1周透析期间动脉硬度不发生变化
Pub Date : 2019-12-04 DOI: 10.1159/000504138
A. Reshetnik, Daniela K. Wrobel, Georg Wirtz, M. Tölle, K. Eckardt, M. van der Giet
Introduction: End-stage renal disease (ESRD) is associated with exponentially elevated cardiovascular mortality. Arterial stiffness (AS) – usually expressed with pulse wave velocity (PWV) – is an established independent predictor of cardiovascular risk beyond the traditional risk factors. Higher PWV values are frequently observed in patients with ESRD. Due to the intrinsic physiologic relationship between PWV and prevailing arterial pressure, PWV can change without relevant changes in the arterial wall structure, and thus an individual pressure-independent expression of PWV is essential. Methods: The study is a single-center observational study. Repeated measurements of blood pressure (BP) and pulse wave analysis were performed during each dialysis session of 1 week. Aortic PWV was then adjusted to 120 mm Hg central systolic BP (PWV120) based on individually determined relationship. PWV120 values were compared between single sessions. Calculation of the PWV120 was performed retrospectively. Results: Fifty-four subjects were included, 61.1% of whom were male. The median age was 75.5 years, and median dialysis vintage was 33.1 months. Mean systolic/diastolic BP was 121.4/70.5 mm Hg, and the median heart rate was 64.6 beats/min. Mean PWV was 10.9 m/s, and mean PWV120 was 11.3 m/s. PWV120 did not change across single dialysis session during 1 week, while systolic, diastolic BP, PWV, and ultrafiltration volume differed significantly. Discussion/Conclusions: Our data suggest that true AS does not change in the short-term course in dialysis patients. The observed changes in PWV are rather associated with BP change due to intrinsic pressure dependence. Our analytical approach represents a novel method for this purpose, which is easy in performance and also applicable for large interventional trials and clinical practice.
终末期肾病(ESRD)与心血管疾病死亡率呈指数上升相关。动脉僵硬度(AS)通常用脉搏波速度(PWV)表示,是除传统危险因素外,公认的心血管危险的独立预测指标。在ESRD患者中经常观察到较高的PWV值。由于PWV与现行动脉压之间存在内在的生理关系,因此PWV可以在动脉壁结构不发生相应变化的情况下发生变化,因此个体PWV的独立于压力的表达是必要的。方法:本研究为单中心观察性研究。在每1周的透析期间重复测量血压(BP)和脉搏波分析。然后根据个人确定的关系将主动脉PWV调整为120 mm Hg中央收缩压(PWV120)。比较单次会话的PWV120值。回顾性计算PWV120。结果:共纳入54例受试者,男性占61.1%。中位年龄为75.5岁,中位透析时间为33.1个月。平均收缩压/舒张压为121.4/70.5 mm Hg,中位心率为64.6次/分。平均PWV为10.9 m/s,平均PWV120为11.3 m/s。在1周的单次透析期间,PWV120没有变化,而收缩压、舒张压、PWV和超滤体积差异显著。讨论/结论:我们的数据表明,真正的AS在透析患者的短期病程中不会改变。由于固有压力依赖性,观察到的PWV变化与BP变化密切相关。我们的分析方法为这一目的提供了一种新颖的方法,该方法易于执行,也适用于大型介入性试验和临床实践。
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引用次数: 4
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Kidney and Blood Pressure Research
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