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Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification. 基于网络药理学和细胞培养实验验证的大黄治疗糖尿病肾病的潜在应用。
IF 4.2 3区 医学 Pub Date : 2024-04-09 DOI: 10.4239/wjd.v15.i3.530
Meng-Ying Che, Ling Yuan, Jiao Min, Duo-Jie Xu, Dou-Dou Lu, Wen-Jing Liu, Kai-Li Wang, Yan-Yan Wang, Yi Nan
Diabetic kidney disease (DKD) is one of the serious complications of diabetes mellitus, and the existing treatments cannot meet the needs of today's patients. Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application. However, the specific mechanism by which it works is still unclear. Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair (NRDP) for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.
糖尿病肾病(DKD)是糖尿病的严重并发症之一,现有的治疗方法无法满足当今患者的需求。经过多年的临床应用,中药对糖尿病肾病的疗效已得到验证。然而,其具体的作用机制仍不清楚。阐明羌活大黄配伍治疗糖尿病的分子机制,将为新药研发提供新的思路。
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引用次数: 0
Diabetes and high-glucose could upregulate the expression of receptor for activated C kinase 1 in retina. 糖尿病和高血糖可上调视网膜中活化 C 激酶 1 受体的表达。
IF 4.2 3区 医学 Pub Date : 2024-04-09 DOI: 10.4239/wjd.v15.i3.519
Jian Tan, Ang Xiao, Lin Yang, Yu-Lin Tao, Yi Shao, Qiong Zhou
Diabetic retinopathy (DR) is a major ocular complication of diabetes mellitus, leading to visual impairment. Retinal pigment epithelium (RPE) injury is a key component of the outer blood retinal barrier, and its damage is an important indicator of DR. Receptor for activated C kinase 1 (RACK1) activates protein kinase C-ε (PKC-ε) to promote the generation of reactive oxygen species (ROS) in RPE cells, leading to apoptosis. Therefore, we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS, thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR.
糖尿病视网膜病变(DR)是糖尿病的主要眼部并发症,可导致视力损伤。视网膜色素上皮(RPE)损伤是视网膜外血屏障的关键组成部分,其损伤是糖尿病视网膜病变的一个重要指标。活化C激酶1受体(RACK1)激活蛋白激酶C-ε(PKC-ε),促进RPE细胞中活性氧(ROS)的生成,导致细胞凋亡。因此,我们推测在缺氧/高血糖条件下,RACK1的激活可能会通过调节PKC-ε/ROS促进RPE细胞凋亡,从而破坏视网膜外血屏障的屏障效应,导致DR的进展。
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引用次数: 0
MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4. MicroRNA-630 通过靶向收费样受体 4 减轻糖尿病肾病大鼠的炎症反应
IF 4.2 3区 医学 Pub Date : 2024-04-09 DOI: 10.4239/wjd.v15.i3.488
Qi-Shun Wu, Dan-Na Zheng, Cheng Ji, Hui Qian, Juan Jin, Qiang He
Diabetic kidney disease (DKD) is a major complication of diabetes mellitus. Renal tubular epithelial cell (TEC) damage, which is strongly associated with the inflammatory response and mesenchymal trans-differentiation, plays a significant role in DKD; However, the precise molecular mechanism is unknown. The recently identified microRNA-630 (miR-630) has been hypothesized to be closely associated with cell migration, apoptosis, and autophagy. However, the association between miR-630 and DKD and the underlying mechanism remain unknown.
糖尿病肾病(DKD)是糖尿病的主要并发症。肾小管上皮细胞(TEC)损伤与炎症反应和间质转分化密切相关,在 DKD 中起着重要作用;然而,其确切的分子机制尚不清楚。最近发现的microRNA-630(miR-630)被认为与细胞迁移、凋亡和自噬密切相关。然而,miR-630 与 DKD 之间的关联及其内在机制仍然未知。
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引用次数: 0
Metabolic disorders in prediabetes: From mechanisms to therapeutic management. 糖尿病前期的代谢紊乱:从机制到治疗管理。
IF 4.2 3区 医学 Pub Date : 2024-04-09 DOI: 10.4239/wjd.v15.i3.361
Wen-Xin Ping, Shan Hu, Jing-Qian Su, Song-Ying Ouyang
Diabetes, one of the world's top ten diseases, is known for its high mortality and complication rates and low cure rate. Prediabetes precedes the onset of diabetes, during which effective treatment can reduce diabetes risk. Prediabetes risk factors include high-calorie and high-fat diets, sedentary lifestyles, and stress. Consequences may include considerable damage to vital organs, including the retina, liver, and kidneys. Interventions for treating prediabetes include a healthy lifestyle diet and pharmacological treatments. However, while these options are effective in the short term, they may fail due to the difficulty of long-term implementation. Medications may also be used to treat prediabetes. This review examines prediabetic treatments, particularly metformin, glucagon-like peptide-1 receptor agonists, sodium glucose cotransporter 2 inhibitors, vitamin D, and herbal medicines. Given the remarkable impact of prediabetes on the progression of diabetes mellitus, it is crucial to intervene promptly and effectively to regulate prediabetes. However, the current body of research on prediabetes is limited, and there is considerable confusion surrounding clinically relevant medications. This paper aims to provide a comprehensive summary of the pathogenesis of pre-diabetes mellitus and its associated therapeutic drugs. The ultimate goal is to facilitate the clinical utilization of medications and achieve efficient and timely control of diabetes mellitus.
糖尿病是世界十大疾病之一,以死亡率高、并发症多、治愈率低而闻名。糖尿病前期是糖尿病发病的前兆,在此期间,有效的治疗可以降低糖尿病风险。糖尿病前期的风险因素包括高热量和高脂肪饮食、久坐不动的生活方式和压力。其后果可能包括对视网膜、肝脏和肾脏等重要器官造成严重损害。治疗糖尿病前期的干预措施包括健康生活饮食和药物治疗。不过,虽然这些方法在短期内有效,但由于难以长期实施,可能会失败。药物也可用于治疗糖尿病前期。本综述探讨了糖尿病前期的治疗方法,尤其是二甲双胍、胰高血糖素样肽-1 受体激动剂、钠葡萄糖共转运体 2 抑制剂、维生素 D 和草药。鉴于糖尿病前期对糖尿病进展的显著影响,及时有效地干预以控制糖尿病前期至关重要。然而,目前关于糖尿病前期的研究还很有限,临床相关药物也相当混乱。本文旨在全面总结糖尿病前期的发病机制及其相关治疗药物。最终目的是方便临床用药,及时有效地控制糖尿病。
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引用次数: 0
Periodontitis: An often-neglected complication of diabetes. 牙周炎:经常被忽视的糖尿病并发症。
IF 4.2 3区 医学 Pub Date : 2024-04-09 DOI: 10.4239/wjd.v15.i3.318
Marina G Kudiyirickal, Joseph M Pappachan
The bidirectional association between type 2 diabetes mellitus (T2DM) and periodontitis is now well established, resulting in periodontal disease being considered as the 6th major complication of diabetes mellitus (DM) after car-diovascular disease, eye disease, neuropathy, nephropathy, and peripheral vascular disease. DM can worsen the virulence and invasiveness of pathogenic oral microbial flora aggravating the local inflammation and infection in those with periodontal disease. On the other hand, the chemical and immunological mediators released into the circulation as part of periodontal inflammation worsen the systemic insulin resistance with worsening of T2DM. Periodontitis if undiagnosed or left untreated can also result in eventual tooth loss. A study by Xu et al in the World Journal of Diabetes examined the predictive factors associated with periodontitis in Chinese patients with T2DM. The prevalence of periodontitis was found to be 75.7% in this study. Based on logistic regression analysis, the predictive factors for higher risk were low tooth brushing frequency [odds ratio (OR) = 4.3], high triglycerides (TG; OR = 3.31), high total cholesterol (TC; OR = 2.87), higher glycated hemoglobin (HbA1c; OR = 2.55), and higher age (OR = 1.05) while higher education level was protective (OR = 0.53). However, the most influential variables were HbA1c followed by age, TC, TG, low education level, brushing frequency, and sex on the random forest model (this model showed higher sensitivity for predicting the risk). A good understanding of the predictors for periodontitis in T2DM patients is important in prevention, early detection of susceptible patients, and intervention to improve periodontal health and enable long-term glycaemic control as observed by Xu et al.
2 型糖尿病(T2DM)与牙周炎之间的双向关联现已得到证实,牙周病被认为是继汽车-心血管疾病、眼病、神经病变、肾病和外周血管疾病之后的糖尿病(DM)第六大并发症。糖尿病会增加口腔致病微生物菌群的毒力和侵袭力,加重牙周病患者的局部炎症和感染。另一方面,牙周炎症释放到血液循环中的化学和免疫介质会加重全身性胰岛素抵抗,导致 T2DM 恶化。牙周炎如果得不到诊断或治疗,最终也会导致牙齿脱落。Xu 等人在《世界糖尿病杂志》(World Journal of Diabetes)上发表的一项研究探讨了 T2DM 中国患者牙周炎的相关预测因素。研究发现,牙周炎的患病率为 75.7%。根据逻辑回归分析,高风险的预测因素包括刷牙频率低[比值比(OR)= 4.3]、甘油三酯(TG)高(OR = 3.31)、总胆固醇(TC)高(OR = 2.87)、糖化血红蛋白(HbA1c)高(OR = 2.55)和年龄高(OR = 1.05),而教育程度高则具有保护作用(OR = 0.53)。然而,在随机森林模型中,影响最大的变量是 HbA1c,其次是年龄、TC、TG、教育程度低、刷牙频率和性别(该模型对预测风险的灵敏度更高)。正如 Xu 等人所观察到的,充分了解 T2DM 患者牙周炎的预测因素对于预防、早期发现易感患者以及干预改善牙周健康和实现长期血糖控制非常重要。
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引用次数: 0
Evaluation of hybrid closed-loop insulin delivery system in type 1 diabetes in real-world clinical practice: One-year observational study. 评估混合闭环胰岛素输送系统在 1 型糖尿病实际临床实践中的应用:为期一年的观察研究。
IF 4.2 3区 医学 Pub Date : 2024-04-09 DOI: 10.4239/wjd.v15.i3.455
Ahmed Eldib, Shilton Dhaver, Karim Kibaa, Astrid Atakov-Castillo, Tareq Salah, Marwa Al-Badri, Abdelrahman Khater, Ryan McCarragher, Omnia Elenani, Elena Toschi, Osama Hamdy
In 2016, the Food and Drug Administration approved the first hybrid closed-loop (HCL) insulin delivery system for adults with type 1 diabetes (T1D). There is limited information on the impact of using HCL systems on patient-reported outcomes (PROs) in patients with T1D in real-world clinical practice. In this independent study, we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic's 670G HCL in real-world clinical practice.
2016 年,美国食品和药物管理局批准了首个用于 1 型糖尿病(T1D)成人患者的混合闭环(HCL)胰岛素给药系统。关于在实际临床实践中使用 HCL 系统对 T1D 患者的患者报告结果(PROs)的影响,目前的信息还很有限。在这项独立研究中,我们评估了在实际临床实践中连续使用美敦力 670G HCL 一年的血糖参数和患者报告结果。
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引用次数: 0
Roles of fibroblast growth factors in the treatment of diabetes. 成纤维细胞生长因子在糖尿病治疗中的作用。
IF 4.2 3区 医学 Pub Date : 2024-04-09 DOI: 10.4239/wjd.v15.i3.392
Chun-Ye Zhang, Ming Yang
Diabetes affects about 422 million people worldwide, causing 1.5 million deaths each year. However, the incidence of diabetes is increasing, including several types of diabetes. Type 1 diabetes (5%-10% of diabetic cases) and type 2 diabetes (90%-95% of diabetic cases) are the main types of diabetes in the clinic. Accumulating evidence shows that the fibroblast growth factor (FGF) family plays important roles in many metabolic disorders, including type 1 and type 2 diabetes. FGF consists of 23 family members (FGF-1-23) in humans. Here, we review current findings of FGFs in the treatment of diabetes and management of diabetic complications. Some FGFs (e.g., FGF-15, FGF-19, and FGF-21) have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes, and their therapeutic roles in diabetes are currently under investigation in clinical trials. Overall, the roles of FGFs in diabetes and diabetic complications are involved in numerous processes. First, FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production. Second, modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components, promote diabetic wound healing process and bone repair, and inhibit cancer cell proliferation and migration. Finally, FGFs can regulate the activation of glucose-excited neurons and the expression of thermogenic genes.
全世界约有 4.22 亿人患有糖尿病,每年造成 150 万人死亡。然而,糖尿病的发病率正在上升,其中包括多种类型的糖尿病。1 型糖尿病(占糖尿病病例的 5%-10%)和 2 型糖尿病(占糖尿病病例的 90%-95%)是临床上主要的糖尿病类型。越来越多的证据表明,成纤维细胞生长因子(FGF)家族在包括 1 型和 2 型糖尿病在内的许多代谢性疾病中发挥着重要作用。在人类中,成纤维细胞生长因子由 23 个家族成员(FGF-1-23)组成。在此,我们回顾了目前有关 FGFs 在治疗糖尿病和控制糖尿病并发症方面的研究成果。一些 FGFs(如 FGF-15、FGF-19 和 FGF-21)已在临床前研究中被广泛用于糖尿病的诊断和治疗,它们在糖尿病中的治疗作用目前正在临床试验中进行研究。总体而言,FGFs 在糖尿病和糖尿病并发症中的作用涉及多个过程。首先,通过调节脂肪组织的脂肪分解和肝糖生成,干预 FGF 可预防高脂饮食引起的肥胖和胰岛素抵抗,降低空腹血糖和甘油三酯水平。其次,调节 FGF 的表达可通过调节细胞外基质成分的表达抑制肾脏和心脏纤维化,促进糖尿病伤口愈合过程和骨修复,抑制癌细胞增殖和迁移。最后,成纤维细胞生长因子可以调节葡萄糖激发神经元的活化和产热基因的表达。
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引用次数: 0
Effects of vitamin family members on insulin resistance and diabetes complications. 维生素家族成员对胰岛素抵抗和糖尿病并发症的影响。
IF 4.2 3区 医学 Pub Date : 2024-04-09 DOI: 10.4239/wjd.v15.i3.568
Hong-Jin Chen, Min Wang, Ding-Min Zou, Gui-You Liang, Si-Yuan Yang
The following letter to the editor highlights the article "Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance" in World J Diabetes 2023 Oct 15; 14 (10): 1514-1523. It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.
以下致编辑的信重点介绍了《世界糖尿病杂志》(World J Diabetes 2023 Oct 15; 14 (10):1514-1523.有必要探讨维生素家族成员在胰岛素抵抗和糖尿病并发症中的作用。
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引用次数: 0
Glucagon-like peptide-1 receptor agonists as a possible intervention to delay the onset of type 1 diabetes: A new horizon. 胰高血糖素样肽-1 受体激动剂作为一种可能的干预措施,可延缓 1 型糖尿病的发病:新视野。
IF 4.2 3区 医学 Pub Date : 2024-02-15 DOI: 10.4239/wjd.v15.i2.133
Mahmoud Nassar, Ajay Chaudhuri, Husam Ghanim, Paresh Dandona

Type 1 diabetes (T1D) is a chronic autoimmune condition that destroys insulin-producing beta cells in the pancreas, leading to insulin deficiency and hyper-glycemia. The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels. However, this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells. Recent research has explored the potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as a novel intervention to modify the disease course and delay the onset of T1D. GLP-1RAs are medications initially developed for treating type 2 diabetes. They exert their effects by enhancing glucose-dependent insulin secretion, suppressing glucagon secretion, and slowing gastric emptying. Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D. This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D, possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells. This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification, which should open new avenues for preventing and treating T1D, improving the quality of life and long-term outcomes for individuals at risk of T1D.

1 型糖尿病(T1D)是一种慢性自身免疫性疾病,会破坏胰腺中产生胰岛素的 beta 细胞,导致胰岛素缺乏和高血糖。T1D 的治疗主要侧重于外源性胰岛素替代,以控制血糖水平。然而,这种方法并不能解决潜在的自身免疫过程,也不能防止贝塔细胞的逐渐丧失。最近的研究探索了胰高血糖素样肽-1 受体激动剂(GLP-1RAs)作为一种新型干预措施的潜力,以改变疾病进程并延缓 T1D 的发病。GLP-1RAs 最初是用于治疗 2 型糖尿病的药物。它们通过增强葡萄糖依赖性胰岛素分泌、抑制胰高血糖素分泌和减缓胃排空来发挥药效。新的证据表明,GLP-1RAs 也可能有益于新诊断的 T1D 患者的治疗。本文旨在强调 GLP-1RAs 作为一种干预措施延缓 T1D 发病的潜力,这可能是通过其潜在的免疫调节和抗炎作用以及对 beta 细胞的保护实现的。本文旨在探讨将 T1D 的治疗模式从被动的胰岛素替代转变为主动的疾病调整的可能性,这将为预防和治疗 T1D、改善 T1D 高危人群的生活质量和长期疗效开辟新的途径。
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引用次数: 0
Urinary exosomal microRNA-145-5p and microRNA-27a-3p act as noninvasive diagnostic biomarkers for diabetic kidney disease 尿液外泌体 microRNA-145-5p 和 microRNA-27a-3p 可作为糖尿病肾病的非侵入性诊断生物标记物
IF 4.2 3区 医学 Pub Date : 2024-01-15 DOI: 10.4239/wjd.v15.i1.92
Lulu Han, Shenghai Wang, Ming-Yan Yao, Hong Zhou
BACKGROUND Diabetic kidney disease (DKD), characterized by increased urinary microalbumin levels and decreased renal function, is the primary cause of end-stage renal disease. Its pathological mechanisms are complicated and multifactorial; Therefore, sensitive and specific biomarkers are needed. Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney. The microRNAs (miRNAs) in urinary exosome are remarkably stable and highly tissue-specific for the kidney. AIM To determine if urinary exosomal miRNAs from diabetic patients can serve as noninvasive biomarkers for early DKD diagnosis. METHODS Type 2 diabetic mellitus (T2DM) patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups: DM, diabetic patients without albuminuria [urinary albumin to creatinine ratio (UACR) < 30 mg/g] and DKD, diabetic patients with albuminuria (UACR ≥ 30 mg/g). Healthy subjects were the normal control (NC) group. Urinary exosomal miR-145-5p, miR-27a-3p, and miR-29c-3p, were detected using real-time quantitative polymerase chain reaction. The correlation between exosomal miRNAs and the clinical indexes was evaluated. The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic (ROC) analysis. Biological functions of miR-145-5p were investigated by performing Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group (miR-145-5p: 4.54 ± 1.45 vs 1.95 ± 0.93, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.71 ± 0.76, P < 0.05) and the NC group (miR-145-5p: 4.54 ± 1.45 vs 1.55 ± 0.83, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.10 ± 0.51, P < 0.001). The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate. miR-27a-3p was also closely related to blood glucose, glycosylated hemoglobin A1c, and low-density lipoprotein cholesterol. ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88 [95% confidence interval (CI): 0.784-0.985, P < 0.0001] in diagnosing DKD than miR-27a-3p with 0.71 (95%CI: 0.547-0.871, P = 0.0239). Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament, cytoskeleton, and extracellular exosome and were involved in the pathological processes of DKD, including apoptosis, inflammation, and fibrosis. CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
背景 糖尿病肾病(DKD)以尿微量白蛋白水平升高和肾功能减退为特征,是终末期肾病的主要病因。其病理机制复杂且多因素,因此需要敏感而特异的生物标记物。尿液外泌体来源于肾小球中不同的肾细胞,部分反映了肾脏的病理变化。尿液外泌体中的微RNA(miRNA)非常稳定,对肾脏组织具有高度特异性。目的 确定糖尿病患者尿液外泌体 miRNA 是否可作为早期诊断 DKD 的无创生物标记物。方法 从河北医科大学第二医院招募 2 型糖尿病(T2DM)患者,将其分为两组:DM:无白蛋白尿的糖尿病患者[尿白蛋白与肌酐比值(UACR)< 30 mg/g];DKD:有白蛋白尿的糖尿病患者(UACR ≥ 30 mg/g)。健康受试者为正常对照(NC)组。采用实时定量聚合酶链反应检测尿液外泌体 miR-145-5p、miR-27a-3p 和 miR-29c-3p。评估了外泌体 miRNA 与临床指标之间的相关性。利用接收器操作特征(ROC)分析确定了外泌体 miR-145-5p 和 miR-27a-3p 在 DKD 中的诊断价值。通过基因本体分析和京都基因和基因组百科全书通路富集研究了 miR-145-5p 的生物学功能。结果 与 DM 组相比,DKD 组的尿液外泌体中 miR-145-5p 和 miR-27a-3p 的表达更高调(miR-145-5p:4.54 ± 1.45 vs 1.95 ± 0.93,P < 0.001;miR-27a-3p:2.33 ± 0.79 vs 1.71 ± 0.76,P < 0.05)和 NC 组(miR-145-5p:4.54 ± 1.45 vs 1.55 ± 0.83,P < 0.001;miR-27a-3p:2.33 ± 0.79 vs 1.10 ± 0.51,P < 0.001)。外泌体miR-145-5p和miR-27a-3p与白蛋白尿和血清肌酐呈正相关,与估计肾小球滤过率呈负相关;miR-27a-3p还与血糖、糖化血红蛋白A1c和低密度脂蛋白胆固醇密切相关。ROC 分析显示,在诊断 DKD 方面,miR-145-5p 的曲线下面积为 0.88 [95% 置信区间 (CI):0.784-0.985,P < 0.0001],优于 miR-27a-3p 的 0.71(95%CI:0.547-0.871,P = 0.0239)。生物信息学分析表明,miR-145-5p 的靶基因位于肌动蛋白丝、细胞骨架和细胞外泌体,参与了 DKD 的病理过程,包括细胞凋亡、炎症和纤维化。结论 尿液外泌体miR-145-5p和miR-27a-3p可作为新型非侵入性诊断生物标志物或有希望成为DKD的治疗靶点。
{"title":"Urinary exosomal microRNA-145-5p and microRNA-27a-3p act as noninvasive diagnostic biomarkers for diabetic kidney disease","authors":"Lulu Han, Shenghai Wang, Ming-Yan Yao, Hong Zhou","doi":"10.4239/wjd.v15.i1.92","DOIUrl":"https://doi.org/10.4239/wjd.v15.i1.92","url":null,"abstract":"BACKGROUND\u0000 Diabetic kidney disease (DKD), characterized by increased urinary microalbumin levels and decreased renal function, is the primary cause of end-stage renal disease. Its pathological mechanisms are complicated and multifactorial; Therefore, sensitive and specific biomarkers are needed. Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney. The microRNAs (miRNAs) in urinary exosome are remarkably stable and highly tissue-specific for the kidney.\u0000 AIM\u0000 To determine if urinary exosomal miRNAs from diabetic patients can serve as noninvasive biomarkers for early DKD diagnosis.\u0000 METHODS\u0000 Type 2 diabetic mellitus (T2DM) patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups: DM, diabetic patients without albuminuria [urinary albumin to creatinine ratio (UACR) < 30 mg/g] and DKD, diabetic patients with albuminuria (UACR ≥ 30 mg/g). Healthy subjects were the normal control (NC) group. Urinary exosomal miR-145-5p, miR-27a-3p, and miR-29c-3p, were detected using real-time quantitative polymerase chain reaction. The correlation between exosomal miRNAs and the clinical indexes was evaluated. The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic (ROC) analysis. Biological functions of miR-145-5p were investigated by performing Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment.\u0000 RESULTS\u0000 Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group (miR-145-5p: 4.54 ± 1.45 vs 1.95 ± 0.93, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.71 ± 0.76, P < 0.05) and the NC group (miR-145-5p: 4.54 ± 1.45 vs 1.55 ± 0.83, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.10 ± 0.51, P < 0.001). The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate. miR-27a-3p was also closely related to blood glucose, glycosylated hemoglobin A1c, and low-density lipoprotein cholesterol. ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88 [95% confidence interval (CI): 0.784-0.985, P < 0.0001] in diagnosing DKD than miR-27a-3p with 0.71 (95%CI: 0.547-0.871, P = 0.0239). Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament, cytoskeleton, and extracellular exosome and were involved in the pathological processes of DKD, including apoptosis, inflammation, and fibrosis.\u0000 CONCLUSION\u0000 Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139529787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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World Journal of Diabetes
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