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慢性肾脏病和终末期肾病中肾祖细胞/干细胞、肾间充质干细胞样细胞和内皮祖细胞的组织学评价,以及药物-受体相互作用的分子对接分析。

Histological evaluation of renal progenitor/stem cells, renal mesenchymal stem-like cells, and endothelial progenitor cells in chronic kidney disease and end-stage renal disease, and molecular docking analysis of drug-receptor interactions.

机构信息

Student Research Committee, Bushehr University of Medical Sciences, Bushehr, Iran.

The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran.

出版信息

Tissue Cell. 2024 Oct;90:102527. doi: 10.1016/j.tice.2024.102527. Epub 2024 Aug 22.

Abstract

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are prevalent and debilitating conditions with a significant impact on patients' quality of life. In this study, we conducted a comprehensive investigation into the histological characteristics of renal progenitor/stem cells (RPCs), renal mesenchymal stem-like cells, and endothelial progenitor cells (EPCs) in CKD and ESRD patients. Additionally, we performed a molecular docking analysis to explore potential drug-receptor interactions involving common medications prescribed to CKD patients. Our histological examination revealed a noteworthy increase in the number of CD24- and CD133-positive cells in CKD and ESRD patients, representing RPCs. These cells are implicated in kidney repair and regeneration, underscoring their potential role in CKD management. Moreover, we observed an elevation in the number of EPCs within the kidneys of CKD and ESRD patients, suggesting a protective role of EPCs in kidney preservation. The molecular docking analysis unveiled intriguing insights into potential drug interventions. Notably, digoxin exhibited the highest in-silico binding affinity to numerous receptors associated with the functions of RPCs, renal mesenchymal stem-like cells, and EPCs, emphasizing the potential multifaceted effects of this cardiac glycoside in CKD patients. Other drugs, including apixaban, glimepiride, and glibenclamide, also displayed strong in-silico affinities to specific receptors, indicating their potential influence on various renal cell functions. In conclusion, this study provides valuable insights into the histological alterations in renal cell populations in CKD and ESRD patients and underscores the potential roles of RPCs and EPCs in kidney repair and preservation. The molecular docking analysis reveals the complex interactions between common drugs and renal cells, suggesting the need for further in-vitro and in-vivo research to fully understand these relationships. These findings contribute to our understanding of CKD and offer new avenues for research into potential therapeutic interventions.

摘要

慢性肾脏病(CKD)和终末期肾病(ESRD)是普遍存在且使人虚弱的疾病,对患者的生活质量有重大影响。在这项研究中,我们对 CKD 和 ESRD 患者的肾祖细胞/干细胞(RPCs)、肾间充质干细胞样细胞和内皮祖细胞(EPCs)的组织学特征进行了全面研究。此外,我们进行了分子对接分析,以探索涉及 CKD 患者常用药物的潜在药物-受体相互作用。我们的组织学检查表明,CD24-和 CD133-阳性细胞(代表 RPCs)在 CKD 和 ESRD 患者中的数量显著增加。这些细胞参与肾脏修复和再生,强调了它们在 CKD 管理中的潜在作用。此外,我们观察到 CKD 和 ESRD 患者肾脏中 EPCs 的数量增加,表明 EPCs 在保护肾脏方面发挥作用。分子对接分析揭示了潜在药物干预的有趣见解。值得注意的是,地高辛对与 RPCs、肾间充质干细胞样细胞和 EPCs 功能相关的众多受体表现出最高的计算机模拟结合亲和力,强调了这种强心苷在 CKD 患者中的多方面潜在作用。其他药物,包括阿哌沙班、格列美脲和格列本脲,也对特定受体表现出强烈的计算机模拟亲和力,表明它们对各种肾细胞功能的潜在影响。总之,这项研究提供了对 CKD 和 ESRD 患者肾脏细胞群体组织学改变的宝贵见解,并强调了 RPCs 和 EPCs 在肾脏修复和保护中的潜在作用。分子对接分析揭示了常见药物与肾脏细胞之间的复杂相互作用,表明需要进一步进行体外和体内研究,以充分了解这些关系。这些发现有助于我们理解 CKD,并为研究潜在的治疗干预提供了新的途径。

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