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Effects of Calamintha incana (Sm.) Helder Ethanolic Extract on the mRNA Expression of Drug-metabolizing cyp450s in the Mouse Livers. Calamintha incana (Sm.) Helder乙醇提取物对小鼠肝脏中药物代谢cyp450s mRNA表达的影响
Pub Date : 2024-01-01 DOI: 10.2174/0122115366268781231205103752
Arwa R Althaher, Yazun Jarrar, Mahmood Ayad Al-Ibadah, Ruba Balasmeh, Qais Jarrar, Dina Abulebdah

Background: Alteration in the expression and activity of drug-metabolizing enzymes (DMEs) can alter the pharmacokinetics and hence the response of the drug. Some chemicals found in herbs and fruits affect the expression of DMEs. Calamintha incana is commonly used in Middle Eastern Arabic countries. There is no report regarding the influence of Calamintha incana on the hepatic expression of DMEs.

Aims: The current investigation aimed to investigate the effect of Calamintha incana consumption on the mRNA expression of major hepatic drug-metabolizing cytochrome (cyp) P450 genes in mice.

Methods: The chemical composition of the ethanoic extract was analyzed using liquid chromatography/ mass spectrometry. Then, 21 BALB/c mice were used for the in vivo experiment. The mice were divided into three groups, each consisting of seven mice. The first group (low-dose group) was treated with 41.6 mg/kg of Calamintha incana extract and the second group was administered the high-dose (125 mg/kg) of the extract for one month. The mice in the third "control" group administrated the vehicle 20% polyethylene glycol 200. Then, the expression of cyp3a11, cyp2c29, cyp2d9, and cyp1a1 was analyzed using the real-time polymerase chain reaction. The relative liver weights of the mice and the hepatic pathohistological alterations were assessed.

Results: The ethanolic extract of Calamintha incana contained 27 phytochemical compounds. The most abundant compounds were linolenic acid, myristic acid, and p-cymene. It was found that the low dose of Calamintha incana extract upregulated significantly (P < 0.05) the expression of cyp3a11 by more than ten folds in the liver of treated mice. Furthermore, the histological analysis showed that low- and high-dose administration of the C. incana did not cause pathological alterations.

Conclusion: It can be concluded from these findings that consumption of low doses of Calamintha incana upregulated the mRNA expression of mouse cyp3a11 without causing histopathological alterations in the livers. Further studies are needed to determine the influence of Calamintha incana on the pharmacokinetics and response of drugs metabolized by cyp3a11.

背景:药物代谢酶(DMEs)表达和活性的改变会改变药物的药代动力学,从而改变药物的反应。草药和水果中的一些化学物质会影响 DMEs 的表达。Calamintha incana 是中东阿拉伯国家常用的草药。目前还没有关于石菖蒲对肝脏 DMEs 表达影响的报告。目的:本研究旨在探讨服用石菖蒲对小鼠肝脏主要药物代谢细胞色素(cyp)P450 基因 mRNA 表达的影响:方法:采用液相色谱/质谱法分析乙酸提取物的化学成分。然后用 21 只 BALB/c 小鼠进行体内实验。小鼠被分为三组,每组七只。第一组(低剂量组)服用 41.6 毫克/千克的石菖蒲提取物,第二组服用高剂量(125 毫克/千克)的石菖蒲提取物,为期一个月。第三 "控制 "组的小鼠使用 20% 聚乙二醇 200 作为载体。然后,使用实时聚合酶链式反应分析cyp3a11、cyp2c29、cyp2d9和cyp1a1的表达。对小鼠肝脏相对重量和肝脏病理组织学改变进行了评估:结果:石菖蒲乙醇提取物中含有 27 种植物化学物质。最丰富的化合物是亚麻酸、肉豆蔻酸和对伞花烃。研究发现,低剂量的石菖蒲提取物能显著(P < 0.05)提高小鼠肝脏中 cyp3a11 的表达量,提高幅度超过 10 倍。此外,组织学分析表明,低剂量和高剂量服用石菖蒲提取物不会导致病理改变:从这些研究结果中可以得出结论,服用低剂量的白千层能上调小鼠 cyp3a11 的 mRNA 表达,但不会导致肝脏组织病理学改变。还需要进一步研究,以确定石菖蒲对由 cyp3a11 代谢的药物的药代动力学和反应的影响。
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引用次数: 0
Non-Canonical Targets of MicroRNAs: Role in Transcriptional Regulation, Disease Pathogenesis and Potential for Therapeutic Targets. MicroRNAs 的非典型靶标:在转录调控、疾病发病机制和潜在治疗靶点中的作用。
Pub Date : 2024-01-01 DOI: 10.2174/0122115366278651240105071533
Aishwarya Ray, Abhisek Sarkar, Sounak Banerjee, Kaushik Biswas

MicroRNAs are a class of regulatory, non-coding small ribonucleic acid (RNA) molecules found in eukaryotes. Dysregulated expression of microRNAs can lead to downregulation or upregulation of their target gene. In general, microRNAs bind with the Argonaute protein and its interacting partners to form a silencing complex. This silencing complex binds with fully or partial complementary sequences in the 3'-UTR of their cognate target mRNAs and leads to degradation of the transcripts or translational inhibition, respectively. However, recent developments point towards the ability of these microRNAs to bind to the promoters, enhancers or coding sequences, leading to upregulation of their target genes. This review briefly summarizes the various non-canonical binding sites of microRNAs and their regulatory roles in various diseased conditions.

微小核糖核酸(microRNA)是一类存在于真核生物中的调节性非编码小核糖核酸(RNA)分子。microRNA 的表达失调可导致其靶基因的下调或上调。一般来说,microRNA 与 Argonaute 蛋白及其相互作用伙伴结合形成沉默复合体。这种沉默复合物与其同源靶 mRNA 的 3'-UTR 中的完全或部分互补序列结合,分别导致转录本降解或翻译抑制。然而,最近的研究表明,这些 microRNA 能够与启动子、增强子或编码序列结合,从而导致其靶基因的上调。本综述简要概述了 microRNA 的各种非规范结合位点及其在各种疾病中的调控作用。
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引用次数: 0
Bioinformatics-Assisted Extraction of All PCa miRNAs and their Target Genes. 生物信息学辅助提取所有 PCa miRNA 及其靶基因
Pub Date : 2024-01-01 DOI: 10.2174/0122115366253242231020053221
Akilandeswari Ramu, Jayaprakash Chinnappan

Introduction: To retrieve, and classify PCa miRNAs and identify the functional relationship between miRNAs and their targets through literature collection with computational analysis.

Background: MicroRNAs play a role in gene regulation, which can either repress or activate the gene. Hence, the functions of miRNAs are dependent on the target gene. This study will be the first of its kind to combine computational analysis with corpus PCa data. Effectively, our study reported the huge number of miRNAs associated with PCa along with functional information.

Objective: The identification and classification of previously known full PCa miRNAs and their targets were made possible by mining the literature data. Systems Biology and curated data mining assisted in identifying optimum miRNAs and their target genes for PCa therapy.

Methods: PubMed database was used to collect the PCa literature up to December 2021. Pubmed. mineR package was used to extract the microRNAs associated articles and manual curation was performed to classify the microRNAs based on the function in PCa. PPI was constructed using the STRING database. Pathway analysis was performed using PANTHER and ToppGene Suite Software. Functional analysis was performed using ShinyGO software. Cluster analysis was performed using MCODE 2.0, and Hub gene analysis was performed using cytoHubba. The genemiRNA network was reconstructed using Cytoscape.

Results: Unique PCa miRNAs were retrieved and classified from mined PCa literature. Six hundred and five unique miRNAs from 250 articles were considered as oncomiRs to trigger PCa. One hundred and twenty unique miRNAs from 118 articles were considered Tumor Suppressor miRNAs to suppress the PCa. Twenty-four unique miRNAs from 22 articles were utilized as treatment miRNAs to treat PCa. miRNAs target genes and their significant pathways, functions and hub genes were identified.

Conclusion: miR-27a, miR-34b, miR-495, miR-23b, miR-100, miR-218, Let-7a family, miR-27a- 5p, miR-34c, miR-34a, miR-143/-145, miR-125b, miR-124 and miR-205 with their target genes AKT1, SRC, CTNNB1, HRAS, MYC and TP53 are significant PCa targets.

目的:通过文献收集和计算分析,检索 PCa miRNAs,并对其进行分类,确定 miRNAs 与其靶标之间的功能关系:背景:microRNAs 在基因调控中起着抑制或激活基因的作用。因此,miRNA 的功能取决于靶基因。这项研究是首次将计算分析与 PCa 数据库相结合。实际上,我们的研究报告了与 PCa 相关的大量 miRNA 及其功能信息:目的:通过挖掘文献数据,对以前已知的PCa miRNA及其靶标进行了鉴定和分类。系统生物学和数据挖掘有助于确定治疗 PCa 的最佳 miRNA 及其靶基因:方法:使用 PubMed 数据库收集截至 2021 年 12 月的 PCa 文献。方法:使用 Pubmed.mineR 软件包提取与 microRNAs 相关的文章,并根据 microRNAs 在 PCa 中的功能对其进行人工分类。使用 STRING 数据库构建 PPI。使用 PANTHER 和 ToppGene Suite 软件进行通路分析。使用 ShinyGO 软件进行功能分析。使用 MCODE 2.0 进行聚类分析,使用 cytoHubba 进行 Hub 基因分析。使用 Cytoscape 重建基因 miRNA 网络:结果:从挖掘到的 PCa 文献中检索到了独特的 PCa miRNA,并对其进行了分类。250 篇文章中的 65 个独特 miRNA 被认为是诱发 PCa 的 oncomiRs。118篇文章中的120个独特miRNA被认为是抑制PCa的肿瘤抑制miRNA。22篇文章中的24个独特的miRNA被认为是治疗PCa的治疗miRNA。结论:miR-27a、miR-34b、miR-495、miR-23b、miR-100、miR-218、Let-7a 家族、miR27a-5p、miR-34c、miR-34a、miR-143/-145、miR-125b、miR-124 和 miR-205 及其靶基因 AKT1、SRC、CTNNB1、HRAS、MYC 和 TP53 是治疗 PCa 的重要靶点。
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引用次数: 0
Comparative Analysis of Published Database Predicting MicroRNA Binding in 3'UTR of mRNA in Diverse Species. 已发表的预测不同物种信使核糖核酸3'UTR中微小核糖核酸结合的数据库的比较分析。
Pub Date : 2024-01-01 DOI: 10.2174/0122115366261005231018070640
Sonu Singh Ahirwar, Rehma Rizwan, Samdish Sethi, Zainab Shahid, Shivani Malviya, Rekha Khandia, Amit Agarwal, Ashwin Kotnis

Background: Micro-RNAs are endogenous non-coding RNA moieties of 22-27 nucleotides that play a crucial role in the regulation of various biological processes and make them useful prognostic and diagnostic biomarkers. Discovery and experimental validation of miRNA is a laborious and time-consuming process. For early prediction, multiple bioinformatics databases are available for miRNA target prediction; however, their utility can confuse amateur researchers in selecting the most appropriate tools for their study.

Objective: This descriptive review aimed to analyse the usability of the existing database based on the following criteria: accessibility, efficiency, interpretability, updatability, and flexibility for miRNA target prediction of 3'UTR of mRNA in diverse species so that the researchers can utilize the database most appropriate to their research.

Methods: A systematic literature search was performed in PubMed, Google Scholar and Scopus databases up to November 2022. ≥10,000 articles found online, including ⁓130 miRNA tools, which contain various information on miRNA. Out of them, 31 databases that provide information on validated 3'UTR miRNAs target databases were included and analysed in this review.

Results: These miRNA database tools are being used in varied areas of biological research to select the most suitable miRNA for their experimental validation. These databases, updated until the year 2021, consist of miRNA-related data from humans, animals, mice, plants, viruses etc. They contain 525-29806351 data entries, and information from most databases is freely available on the online platform.

Conclusion: Reviewed databases provide significant information, but not all information is accurate or up-to-date. Therefore, Diana-TarBase and miRWalk are the most comprehensive and up-to-date databases.

背景:微小RNA是22-27个核苷酸的内源性非编码RNA部分,在各种生物过程的调节中起着至关重要的作用,使其成为有用的预后和诊断生物标志物。miRNA的发现和实验验证是一个费时费力的过程。对于早期预测,多个生物信息学数据库可用于miRNA靶点预测;然而,它们的实用性可能会让业余研究人员在选择最合适的研究工具时感到困惑。目的:本描述性综述旨在基于以下标准分析现有数据库的可用性:可访问性、效率、可解释性、可更新性和灵活性,用于预测不同物种中信使核糖核酸3'UTR的miRNA靶点,以便研究人员能够利用最适合其研究的数据库。方法:截至2022年11月,在PubMed、Google Scholar和Scopus数据库中进行系统的文献检索网上发现的10000篇文章,包括⁓130 miRNA工具,其中包含有关miRNA的各种信息。其中,31个数据库提供了有关已验证的3’UTR miRNA靶数据库的信息,并在本综述中进行了分析。结果:这些miRNA数据库工具被用于生物学研究的各个领域,以选择最合适的miRNA进行实验验证。这些数据库更新至2021年,由来自人类、动物、小鼠、植物、病毒等的miRNA相关数据组成。它们包含525-29806351个数据条目,大多数数据库的信息可以在在线平台上免费获得。结论:经过审查的数据库提供了重要信息,但并非所有信息都是准确或最新的。因此,Diana TarBase和miRWalk是最全面、最新的数据库。
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引用次数: 0
Meet Our Regional Editor 认识我们的地区编辑
Pub Date : 2023-03-01 DOI: 10.2174/221153661201230206152903
A. van den Berg
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引用次数: 0
Small Molecules have Great Benefits. The Arising of microRNA in LifeSciences and Medicine 小分子有大好处。microRNA在生命科学和医学中的应用
Pub Date : 2023-03-01 DOI: 10.2174/221153661201230206154732
Izzotti A
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引用次数: 0
Evaluation of Expression Profile of Patients with Acute Myeloid Leukemia in Response to Azacitidine with Biological System Approach. 用生物系统法评价急性髓系白血病患者对阿扎胞苷的表达谱。
Pub Date : 2023-01-01 DOI: 10.2174/2211536612666230825152826
Rasta Hejab, Hamzeh Rahimi, Hamid Abedinlou, Pegah Ghoraeian

Background: Acute myeloid leukemia (AML) is a prevalent type of leukemia that is associated with high rates of chemoresistance, including resistance to Azacitidine (AZA). Understanding the molecular mechanisms of chemoresistance can lead to the development of novel therapeutic approaches. In this study, we aimed to identify dysregulated miRNAs and their target genes involved in chemoresistance to AZA in AML patients.

Methods: We analyzed expression profiles from two GEO datasets (GSE16625 and GSE77750) using the "Limma" package in R. We identified 29 differentially expressed miRNAs between AML patients treated with AZA and healthy individuals. MultiMiR package of R was used to predict target genes of identified miRNAs, and functional enrichment analysis was performed using FunRich software. Protein-protein interaction networks were constructed using STRING and visualized using Cytoscape. MiR-582 and miR- 597 were the most up- and down-regulated miRNAs, respectively. Functional enrichment analysis revealed that metal ion binding, regulation of translation, and proteoglycan syndecan-mediated signaling events were the most enriched pathways. The tumor necrosis factor (TNF) gene was identified as a hub gene in the protein-protein interaction network.

Discussion: Our study identified dysregulated miRNAs and their target genes in response to AZA treatment in AML patients. These findings provide insights into the molecular mechanisms of chemoresistance and suggest potential therapeutic targets for the treatment of AML.

Conclusion: Further experimental validation of the identified miRNAs and their targets is warranted.

背景:急性髓系白血病(AML)是一种常见的白血病类型,与高耐药率相关,包括对阿扎胞苷(AZA)的耐药。了解化疗耐药的分子机制可以导致新的治疗方法的发展。在这项研究中,我们旨在鉴定AML患者中参与AZA化疗耐药的异常mirna及其靶基因。方法:我们使用r中的“Limma”软件包分析了两个GEO数据集(GSE16625和GSE77750)的表达谱。我们在接受AZA治疗的AML患者和健康个体之间鉴定了29种差异表达的mirna。使用R的MultiMiR包预测鉴定的miRNAs的靶基因,并使用FunRich软件进行功能富集分析。使用STRING构建蛋白-蛋白相互作用网络,并使用Cytoscape进行可视化。miR- 582和miR- 597分别是上调和下调最多的mirna。功能富集分析显示,金属离子结合、翻译调控和蛋白聚糖syndecan介导的信号通路富集最多。肿瘤坏死因子(TNF)基因被确定为蛋白-蛋白相互作用网络中的枢纽基因。讨论:我们的研究确定了AML患者对AZA治疗的反应中失调的mirna及其靶基因。这些发现为化疗耐药的分子机制提供了见解,并为AML的治疗提供了潜在的治疗靶点。结论:对鉴定的mirna及其靶标进行进一步的实验验证是必要的。
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引用次数: 0
MicroRNA Expression Profile Separates Squamous Cell Carcinoma by Mode of Differentiation. 微小RNA表达谱通过分化模式分离鳞状细胞癌。
Pub Date : 2023-01-01 DOI: 10.2174/2211536612666230418103004
Andani Marumo, Adam Botha, Julitha Molepo, Henry Adeola, Pumza Samantha Maganagane, Mulalo Molaudzi

Background: Squamous cell carcinoma (SCC) is a non-melanoma skin cancer with several risk factors including age and sun exposure. The degree of histological differentiation is considered an independent predictor of recurrence, metastasis, and survival. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in regulating gene expression, culminating in the initiation and progression of multiple tumors. The aim of this study was to determine changes in miRNA expression as a result of the mode of differentiation in SCC.

Methods: We analyzed 29 SCC samples that were separated by mode of differentiation into well (n=4), moderate (n=20) and poor (n=5). Of the 29 samples, five had matched normal tissues, which were used as controls. Total RNA was extracted using the RNeasy FFPE kit, and miRNAs were quantified using Qiagen MiRCURY LNA miRNA PCR Assays. Ten miRNAs (hsa-miR-21, hsa-miR-146b-3p, hsa-miR-155-5p, hsa-miR-451a, hsa-miR-196-5p, hsa-miR-221-5p, hsa-miR-375, hsa-miR-205-5p, hsa-let-7d-5p and hsa-miR-491-5p) that have been previously differentiated in cancer, were quantified. A fold regulation above 1 indicated upregulation and below 1, downregulation.

Results: Hierarchical clustering showed that the miRNA expression profile in the moderately differentiated group was similar to the well-differentiated group. The miRNA with the greatest upregulation in the moderate group was hsa-miR-375, while in the well group, hsa-miR-491-5p showed the greatest downregulation.

Conclusion: In conclusion, this study observed that the well and moderate groups had similar microRNA expression patterns compared to the poorly differentiated group. MicroRNA expression profiling may be used to better understand the factors underpinning mode of differentiation in SCC.

背景:鳞状细胞癌(SCC)是一种癌症,有多种危险因素,包括年龄和日晒。组织学分化程度被认为是复发、转移和生存的独立预测因素。微小RNA(miRNA)是一种小型非编码RNA,在调节基因表达中发挥重要作用,最终导致多发性肿瘤的发生和发展。本研究的目的是确定SCC分化模式导致的miRNA表达的变化。方法:我们分析了29个SCC样本,这些样本按分化模式分为良(n=4)、中(n=20)和差(n=5)。在29个样本中,有5个样本与正常组织匹配,作为对照。使用RNeasy FFPE试剂盒提取总RNA,并使用Qiagen MiRCURY LNA miRNA PCR分析对miRNA进行定量。对先前在癌症中分化的10种miRNA(hsa-miR-21、hsa-miR-146b-3p、hsa-iR-155-5p、hsa-miR-451a、hsa--miR-196-5p、hsa-miR-221-5p、hsa-1miR-375、hsa-miR-205-5p、hsa-let-7d-5p和hsa-miR-491-5p)进行定量。倍数调节高于1表示上调,低于1表示下调。结果:分层聚类显示,中分化组和高分化组的miRNA表达谱相似。中度组中上调最大的miRNA是hsa-miR-375,而在正常组中,hsa-miR-491-5p表现出最大的下调。结论:总之,本研究观察到,与低分化组相比,高分化组和中分化组具有相似的微小RNA表达模式。微RNA表达谱可用于更好地了解SCC分化模式的基础因素。
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引用次数: 0
MicroRNA-Mediated Regulation of BMP Signaling in the Developing Neural Tube. 微RNA介导的发育中神经管中BMP信号的调控
Pub Date : 2023-01-01 DOI: 10.2174/2211536611666220930151322
Partha Mukhopadhyay, Ratnam S Seelan, Robert M Greene, M Michele Pisano

Background: Neural tube (NT) morphogenesis is reliant on the proper temporospatial expression of numerous genes and synchronized crosstalk between diverse signaling cascades and gene regulatory networks governing key cellular processes. MicroRNAs (miRNAs), a group of small non-coding regulatory RNAs, execute defining roles in directing key canonical pathways during embryogenesis.

Objective: In order to comprehend the mechanistic underpinnings of miRNA regulation of NT morphogenesis, we have identified in the current study various miRNAs and their target mRNAs associated with BMP signaling during critical stages of neurulation.

Methods: We previously demonstrated the expression of several miRNAs during the critical stages of neurulation (gestational days (GD) 8.5, 9.0, and 9.5) employing high-sensitivity, high-coverage microarrays. In the present study, bioinformatic analyses were used to identify miRNAs differentially expressed (DE) in the embryonic NT that target messenger RNAs (mRNAs) associated with the bone morphogenetic protein (BMP) signaling pathway. RNAs extracted from the developing NT were hybridized to both miRNA and mRNA arrays to evaluate miRNA-mRNA interactions.

Results: Bioinformatic analysis identified several DE miRNAs that targeted mRNAs encoding members of (and proteins associated with) the BMP signaling pathway - a signaling cascade central to normal NT development.

Conclusion: Identification of the miRNAs and their mRNA targets associated with BMP signaling facilitates a better understanding of the crucial epigenetic mechanisms underlying normal NT development as well as the pathogenesis of NT defects. The current study supports the notion that miRNAs function as key regulators of neural tube morphogenesis via modulation of the BMP signaling cascade. Altered expression of these miRNAs during neurulation may therefore result in NT defects.

背景:神经管(NT)的形态发生有赖于众多基因在时间空间上的正确表达,以及各种信号级联和基因调控网络之间的同步串扰,从而控制关键的细胞过程。微小RNA(miRNA)是一组小型非编码调控RNA,在胚胎发生过程中发挥着指导关键规范通路的决定性作用:为了理解miRNA调控NT形态发生的机理基础,我们在本研究中鉴定了神经形成关键阶段与BMP信号相关的各种miRNA及其靶mRNA:方法:我们先前利用高灵敏度、高覆盖率的芯片研究了神经发育关键期(妊娠天数(GD)8.5、9.0和9.5)中几种miRNA的表达。本研究利用生物信息学分析鉴定了胚胎 NT 中针对与骨形态发生蛋白(BMP)信号通路相关的信使 RNA(mRNA)的 miRNA 差异表达(DE)。从发育中的NT提取的RNA与miRNA和mRNA阵列杂交,以评估miRNA与mRNA之间的相互作用:结果:生物信息学分析发现了几个DE miRNA,它们靶向编码BMP信号通路成员(和相关蛋白)的mRNA,BMP信号通路是正常NT发育的核心信号级联:鉴定与 BMP 信号转导相关的 miRNA 及其 mRNA 靶标有助于更好地了解 NT 正常发育的关键表观遗传机制以及 NT 缺陷的发病机制。目前的研究支持这样一种观点,即 miRNA 通过调节 BMP 信号级联而成为神经管形态发生的关键调控因子。因此,这些 miRNA 在神经发育过程中的表达改变可能会导致 NT 缺陷。
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引用次数: 0
Distinct MicroRNAs Identified in Rabbit Blood Arising from Induced Diabetes and a Surgically Simulated Diabetic Ischemia Complication. 诱导糖尿病和手术模拟糖尿病缺血并发症在兔血液中发现的不同microrna。
Pub Date : 2023-01-01 DOI: 10.2174/2211536611666221005091351
Girish J Kotwal, Sabine Waigel, Julia Chariker, Eric Rouchka, Sufan Chien

Background: Diabetic complications have been studied extensively in recent years. There are very few biomarkers in body fluids that can pinpoint a distinct diabetic complication due to insufficient known specific biomarkers for ischemia.

Objective: Identifying microRNA in animal models for each complication could enable early diagnosis of a given complication if verified in humans. MicroRNA (miRNA) profiling has been done in rodent models for a number of diabetic complications, like diabetic glomerular injury, atherosclerosis, cognitive impairment, diabetic wound healing, angiopathy and other complications. Due to multiple differences between rodents and humans, the changes in rabbit skin, considered closer to humans than even pigs, may better simulate human diabetic complications of ischemia.

Methods: To study the miRNA profile of rabbits in which diabetes was induced or ischemia was surgically generated, we studied whether diabetes or ischemia-induced specific miRNA could be detected. MicroRNA from the blood of diabetic rabbits and rabbits with local ischemia was collected in PAXgene Blood RNA tubes specifically designed for miRNA isolation and extracted using the PAX gene miRNA extraction kit. The isolated RNA was quality controlled using an RNA analyzer, and further, using RNA seq technology, it was analyzed for distinct miRNAs that were detected in diabetic and non-diabetic rabbits induced with ischemia.

Results: A miRNA that was found to be expressed in diabetic rabbits and ischemic rabbits but not in untreated rabbits was miRNA-183. Several miRNAs were differentially expressed across comparison groups, and several upregulated miRNAs were identified being unique to each comparison. In rabbits with a potential diabetic complication of a long-term ischemic model, there was one distinct microRNA, which was highly significantly upregulated in ischemia rabbit (miRNA-133-3p). One miRNA that was highly significantly upregulated in diabetic rabbit but not in ischemic rabbits was miRNA-3074-5p. Only statistically significant results have been considered and analyzed.

Conclusion: These findings could lead to a precise and timely diagnosis of a potential single diabetic complication without invasive tissue biopsies and could be a novel tool in the management of diabetic patients developing complications due to the progression of diabetes.

背景:近年来,糖尿病并发症得到了广泛的研究。由于缺乏已知的缺血特异性生物标志物,体液中很少有生物标志物可以精确定位明显的糖尿病并发症。目的:在动物模型中鉴定每种并发症的microRNA,如果在人类中得到证实,可以早期诊断给定的并发症。MicroRNA (miRNA)谱分析已经在啮齿动物模型中完成了许多糖尿病并发症,如糖尿病肾小球损伤、动脉粥样硬化、认知障碍、糖尿病伤口愈合、血管病变和其他并发症。由于啮齿类动物和人类之间存在多种差异,兔子皮肤的变化被认为比猪更接近人类,可能更好地模拟人类糖尿病缺血并发症。方法:研究糖尿病或手术致缺血家兔的miRNA谱,研究是否能检测到糖尿病或缺血诱导的特异性miRNA。从糖尿病家兔和局部缺血家兔的血液中采集MicroRNA,用专门设计的PAXgene血液RNA管分离miRNA,用PAX基因miRNA提取试剂盒提取。利用RNA分析仪对分离的RNA进行质量控制,并利用RNA seq技术分析在缺血诱导的糖尿病和非糖尿病家兔中检测到的不同miRNAs。结果:在糖尿病家兔和缺血家兔中有表达,而在未治疗家兔中无表达的miRNA-183。几个mirna在对照组中表达差异,并且在每个比较中鉴定出几个上调的mirna是独特的。在长期缺血模型的潜在糖尿病并发症家兔中,有一种独特的microRNA在缺血家兔中高度显著上调(miRNA-133-3p)。有一个miRNA-3074-5p在糖尿病家兔中显著上调,而在缺血家兔中没有上调。只有统计上显著的结果才被考虑和分析。结论:这些发现可以在没有侵入性组织活检的情况下准确及时地诊断潜在的单一糖尿病并发症,并可能成为管理因糖尿病进展而出现并发症的糖尿病患者的新工具。
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引用次数: 0
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MicroRNA (Shariqah, United Arab Emirates)
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