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Identification of Prognostic Biomarkers in Papillary Thyroid Cancer and Developing Non-Invasive Diagnostic Models Through Integrated Bioinformatics Analysis. 通过综合生物信息学分析鉴定甲状腺乳头状癌预后生物标志物并建立无创诊断模型。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220124115445
Afsaneh Arefi Oskouie, Mohammad Saeed Ahmadi, Amir Taherkhani
BACKGROUNDPapillary thyroid cancer (PTC) is the most frequent subtype of thyroid carcinoma, mainly detected in patients with benign thyroid nodules (BTN). Due to the invasiveness of accurate diagnostic tests, there is a need to discover applicable biomarkers for PTC. So, in this study, we aimed to identify the genes associated with prognosis in PTC. Besides, we performed a machine learning tool to develop a non-invasive diagnostic approach for PTC.METHODSFor the study's purposes, the miRNA dataset GSE130512 was downloaded from the GEO database and then analyzed to identify the common differentially expressed miRNAs in patients with non-metastatic PTC (nm-PTC)/metastatic PTC (m-PTC) compared with BTNs. The SVM was also applied to differentiate patients with PTC from those patients with BTN using the common DEMs. A protein-protein interaction network was also constructed based on the targets of the common DEMs. Next, functional analysis was performed, the hub genes were determined, and survival analysis was then executed.RESULTSA total of three common miRNAs were found to be differentially expressed among patients with nm-PTC/m-PTC compared with BTNs. In addition, it was established that the autophagosome maturation, ciliary basal body-plasma membrane docking, antigen processing as ubiquitination & proteasome degradation, and class I MHC mediated antigen processing & presentation are associated with the pathogenesis of PTC. Furthermore, it was illustrated that RPS6KB1, CCNT1, SP1, and CHD4 might serve as new potential biomarkers for PTC prognosis.CONCLUSIONSRPS6KB1, CCNT1, SP1, and CHD4 may be considered as new potential biomarkers used for prognostic aims in PTC. However, performing validation tests is inevitable in the future.
背景:甲状腺乳头状癌(PTC)是最常见的甲状腺癌亚型,主要见于良性甲状腺结节(BTN)患者。由于准确诊断测试的侵入性,有必要发现适用于PTC的生物标志物。因此,在本研究中,我们旨在确定与PTC预后相关的基因。此外,我们使用机器学习工具来开发PTC的非侵入性诊断方法。方法:为了研究目的,从GEO数据库下载miRNA数据集GSE130512,然后分析非转移性PTC (nm-PTC)/转移性PTC (m-PTC)患者与btn患者的共同差异表达miRNA。支持向量机也被用于区分PTC患者和BTN患者使用常见的dem。基于常见dem的靶点,构建了蛋白-蛋白相互作用网络。接下来,进行功能分析,确定中心基因,然后进行生存分析。结果:与btn相比,nm-PTC/m-PTC患者中共有3种常见的mirna存在差异表达。此外,我们还发现自噬体成熟、纤毛基底体-质膜对接、泛素化和蛋白酶体降解等抗原加工和I类MHC介导的抗原加工和递呈与PTC的发病机制有关。此外,RPS6KB1、CCNT1、SP1和CHD4可能作为PTC预后的新的潜在生物标志物。结论:RPS6KB1、CCNT1、SP1和CHD4可能被认为是用于PTC预后目标的新的潜在生物标志物。然而,执行验证测试在将来是不可避免的。
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引用次数: 4
Screening and in Silico Functional Analysis of MiRNAs Associated with Acute Myeloid Leukemia Relapse. 与急性髓性白血病复发相关的mirna的筛选和计算机功能分析。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220511160502
Ali Amini Fard, Hamzeh Rahimi, Zinat Shams, Pegah Ghoraeian

Background: Hematologic malignancies are among fatal diseases with different subtypes. Acute myeloid leukemia (AML) is a subtype showing a high invasion rate to different tissues.

Objective: AML patients, even after treatment, show an increased rate of recurrence, and this relapsed profile of AML has turned this malignancy into big challenges in the medical scope.

Methods: In the current study, we aimed to investigate hub-genes and potential signaling pathways in AML recurrence. Two expression profiles of genes and non-coding RNAs were extracted from the Gene Expression Omnibus (GEO) database. Target genes of identified miRNAs were predicted through bioinformatics tools. GO and KEGG pathway enrichment analyses were conducted to discover common target genes and differentially expressed genes. Protein-protein interaction (PPI) network was constructed and visualized through the STRING online database and Cytoscape software, respectively. Hub-genes of constructed PPI were found through the CytoHubba plugin of Cytoscape software.

Results: As a result, 109 differentially expressed genes and 45 differentially expressed miRNAs were found, and the top enriched pathways were immune response, xhemokine activity, immune System, and plasma membrane. The hub-genes were TNF, IL6, TLR4, VEGFA, PTPRC, TLR7, TLR1, CD44, CASP1, and CD68.

Conclusion: The present investigation based on the in silico analysis and microarray GEO databases may provide a novel understanding of the mechanisms related to AML relapse.

背景:血液恶性肿瘤是具有不同亚型的致死性疾病之一。急性髓性白血病(AML)是一种对不同组织具有高侵袭率的亚型。目的:AML患者即使经过治疗,其复发率仍呈上升趋势,AML的这种复发特征使其成为医学领域的一大挑战。方法:在当前的研究中,我们旨在研究中心基因和潜在的AML复发信号通路。从Gene expression Omnibus (GEO)数据库中提取基因和非编码rna的两个表达谱。通过生物信息学工具预测鉴定的mirna的靶基因。通过GO和KEGG途径富集分析,发现共同靶基因和差异表达基因。通过STRING在线数据库和Cytoscape软件分别构建和可视化蛋白质-蛋白质相互作用(PPI)网络。通过Cytoscape软件的CytoHubba插件找到构建的PPI的中心基因。结果:共发现109个差异表达基因和45个差异表达mirna,富集最多的途径为免疫应答、趋化因子活性、免疫系统和质膜。中心基因为TNF、IL6、TLR4、VEGFA、PTPRC、TLR7、TLR1、CD44、CASP1和CD68。结论:目前基于芯片分析和微阵列GEO数据库的研究可能为AML复发相关机制提供新的理解。
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引用次数: 1
Perspectives on Epigenetic Markers in Adaptation to Physical Exercise. 体育运动适应的表观遗传标记研究进展
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220318140844
Robert Solsona, Fabio Borrani, Henri Bernardi, Anthony M J Sanchez
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引用次数: 0
Novel Biomarkers of microRNAs in Gastric Cancer: An Overview from Diagnosis to Treatment. 胃癌中微小rna的新生物标志物:从诊断到治疗的综述。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220322160242
Ebrahim Mirzajani, Sogand Vahidi, Seyedeh Elham Norollahi, Ali Akbar Samadani

Gastric cancer (GC) is the fourth most frequent disease in the world and the second cause of cancer-related death. In this way, over 80% of diagnoses are made in the middle to advanced degrees of the disease, underscoring the requirement for innovative biomarkers that can be identified quickly. Meaningly, biomarkers that can complement endoscopic diagnosis and be used to detect patients with a high risk of GC are desperately needed. These biomarkers will allow for the accurate prediction of therapy response and prognosis in GC patients, as well as the development of an optimal treatment strategy for each individual. Conspicuously, microRNAs (miRNAs) and small noncoding RNA regulate the expression of target mRNA, thereby modifying critical biological mechanisms. According to the data, abnormally miRNAs expression in GC is linked to tumor growth, carcinogenesis, aggression, and distant metastasis. Importantly, miRNA expression patterns and nextgeneration sequencing (NGS) can also be applied to analyze different kinds of tissues and cancers. Given the high death rates and poor prognosis of GC, and the absence of a clinical diagnostic factor that is adequately sensitive to GC, research on novel sensitive and specific markers for GC diagnosis is critical. In this review, we examine the latest research findings that suggest the feasibility and clinical utility of miRNAs in GC.

胃癌(GC)是世界上第四大常见疾病,也是第二大癌症相关死亡原因。通过这种方式,超过80%的诊断是在疾病的中晚期进行的,这强调了对能够快速识别的创新生物标志物的需求。这意味着,迫切需要能够补充内镜诊断并用于检测胃癌高风险患者的生物标志物。这些生物标志物将允许准确预测胃癌患者的治疗反应和预后,以及为每个个体制定最佳治疗策略。值得注意的是,microRNAs (miRNAs)和小非编码RNA调节靶mRNA的表达,从而改变关键的生物学机制。根据这些数据,GC中异常的miRNAs表达与肿瘤生长、癌变、侵袭和远处转移有关。重要的是,miRNA表达模式和下一代测序(NGS)也可以用于分析不同类型的组织和癌症。鉴于胃癌死亡率高、预后差,且缺乏对胃癌足够敏感的临床诊断因素,研究新的敏感特异性标志物对胃癌的诊断至关重要。在这篇综述中,我们回顾了最新的研究结果,表明miRNAs在GC中的可行性和临床应用。
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引用次数: 1
Downregulation of miR-125a-5p Leads to STAT3 Increased Expression in Breast Cancer Patients. miR-125a-5p下调导致STAT3在乳腺癌患者中的表达升高。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220907125812
Negar Shafagh Shishavan, Soheila Talesh Sasani, Zivar Salehi, Masoumeh Rezaei Azhang

Background: Breast cancer (BC) is one of the main causes of cancer-related death in women worldwide. It is necessary to find methods for prognosis and early detection of BC. MicroRNAs inhibit the expression of special target genes at the post-transcriptional stage and have a fundamental role in various cancers. They function as oncogenes or tumor suppressors. MiR-125a- 5p acts as a tumor suppressor in some cancers through a signal transducer and activator of transcription 3 (STAT3) suppression. STAT3 is activated in response to cytokines and growth factors, affecting the transcription of target genes.

Objective: We examined the association between miR-125a-5p and STAT3 expression levels in breast cancer patients for the first time through a case-control study on an Iranian population.

Methods: Total RNAs were extracted from breast cancer and healthy tissues using TRIzol Reagent. Complementary DNA synthesis was performed, and Real-time PCR was done using miR-125a and STAT3-specific primers. GAPDH and U48 genes were used as internal controls. Statistical analysis of the results was conducted by SPSS v.19.0 software.

Results: We obtained a significant association between miR-125a-5p down-regulation and breast cancer disease (0.4333 in patients vs. 1.656 in controls, p-value = 0.009). STAT3 expression was significantly up-regulated in BC samples relative to healthy subjects (1.324 vs. 0.6557, respectively) and p-value <0.0001.

Conclusion: We investigated that decreased miR-125a-5p expression levels were significantly associated with increased STAT3 expression in BC tissues. Therefore, the expression changes of miR- 125a-5p can be an important potential biomarker for early diagnosis of breast cancer. Also, the miRNA molecule may have serious therapeutic potential.

背景:乳腺癌(BC)是全世界女性癌症相关死亡的主要原因之一。寻找预后和早期发现BC的方法是必要的。MicroRNAs在转录后阶段抑制特殊靶基因的表达,在各种癌症中起着重要作用。它们的功能是致癌基因或肿瘤抑制因子。MiR-125a- 5p在某些癌症中通过信号换能器和转录3激活因子(STAT3)抑制发挥肿瘤抑制作用。STAT3在细胞因子和生长因子的作用下被激活,影响靶基因的转录。目的:我们首次通过对伊朗人群的病例对照研究,研究了乳腺癌患者中miR-125a-5p和STAT3表达水平之间的关系。方法:采用TRIzol试剂从乳腺癌组织和健康组织中提取总rna。进行互补DNA合成,使用miR-125a和stat3特异性引物进行Real-time PCR。以GAPDH和U48基因为内对照。采用SPSS v.19.0软件对结果进行统计分析。结果:我们获得了miR-125a-5p下调与乳腺癌疾病之间的显著相关性(患者0.4333 vs对照组1.656,p值= 0.009)。与健康受试者相比,BC样本中STAT3的表达水平显著上调(分别为1.324 vs. 0.6557), p值为p值。结论:我们研究了miR-125a-5p表达水平的降低与BC组织中STAT3表达水平的升高显著相关。因此miR- 125a-5p的表达变化可作为乳腺癌早期诊断的重要潜在生物标志物。此外,miRNA分子可能具有严重的治疗潜力。
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引用次数: 0
The Role, Significance, and Association of MicroRNA-10a/b in Physiology of Cancer. MicroRNA-10a/b在肿瘤生理中的作用、意义和关联
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220523104408
Khaled M Elgeshy, Abdel Hady A Abdel Wahab

MicroRNAs (miRNAs) are small non-coding RNAs that regulate the translation of mRNA and protein, mainly at the posttranscriptional level. Global expression profiling of miRNAs has demonstrated a broad spectrum of aberrations that correlated with several diseases, and miRNA- 10a and miRNA-10b were the first examined miRNAs to be involved in abnormal activities upon dysregulation, including many types of cancers and progressive diseases. It is expected that the same miRNAs behave inconsistently within different types of cancer. This review aims to provide a set of information about our updated understanding of miRNA-10a and miRNA-10b and their clinical significance, molecular targets, current research gaps, and possible future applications of such potent regulators.

MicroRNAs (miRNAs)是一种小的非编码rna,主要在转录后水平调控mRNA和蛋白质的翻译。miRNA的全球表达谱显示了与多种疾病相关的广泛的畸变,miRNA- 10a和miRNA-10b是第一个被研究的涉及异常活动的miRNA,包括许多类型的癌症和进行性疾病。预计相同的mirna在不同类型的癌症中表现不一致。这篇综述旨在提供我们对miRNA-10a和miRNA-10b的最新认识及其临床意义、分子靶点、目前的研究空白以及这些强效调节剂未来可能的应用。
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引用次数: 0
The Interaction Network of MicroRNAs with Cytokines and Signaling Pathways in Allergic Asthma. 过敏性哮喘中microrna与细胞因子及信号通路的相互作用网络。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220428134324
Ali Farmanzadeh, Durdi Qujeq, Tooba Yousefi

Allergic asthma is a complicated disease that is affected by many factors. Numerous cytokines and signaling pathways are attributed to the cause of asthma symptoms. MicroRNAs (miRNAs) are a group of small non-coding single-stranded RNA molecules that are involved in gene silencing and posttranscriptional regulation of gene expression by targeting mRNAs. In pathological conditions, altered expression of microRNAs differentially regulates cytokines and signaling pathways and therefore, can be the underlying reason for the pathogenesis of allergic asthma. Indeed, microRNAs participate in airway inflammation via inducing airway structural cells and activating immune responses by targeting cytokines and signaling pathways. Thus, to make a complete understanding of allergic asthma, it is necessary to investigate the communication network of microRNAs with cytokines and signaling pathways which is contributed to the pathogenesis of allergic asthma. Here, we shed light on this aspect of asthma pathology by Summarizing our current knowledge of this topic.

过敏性哮喘是一种受多种因素影响的复杂疾病。许多细胞因子和信号通路被认为是引起哮喘症状的原因。MicroRNAs (miRNAs)是一组小的非编码单链RNA分子,通过靶向mrna参与基因沉默和基因表达的转录后调控。在病理条件下,microrna表达的改变对细胞因子和信号通路进行了差异调节,因此可能是过敏性哮喘发病的潜在原因。事实上,microRNAs通过靶向细胞因子和信号通路,诱导气道结构细胞和激活免疫反应,参与气道炎症。因此,为了全面了解变应性哮喘,有必要研究与变应性哮喘发病机制有关的microrna与细胞因子和信号通路的通讯网络。在这里,我们通过总结我们目前对这一主题的知识来阐明哮喘病理学的这一方面。
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引用次数: 2
The Core Human MicroRNAs Regulated by Toxoplasma gondii. 刚地弓形虫调控的核心人类microrna。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220428130250
Neelam Antil, Mohammad Arefian, Mrudula Kinarulla Kandiyil, Kriti Awasthi, Thottethodi Subrahmanya Keshava Prasad, Rajesh Raju

Background: Toxoplasma gondii (T. gondii) is an intracellular zoonotic protozoan parasite known to effectively modulate the host system for its survival. A large number of microRNAs (miRNAs) regulated by different strains of T. gondii in diverse types of host cells/tissues/organs have been reported across multiple studies.

Objective: We aimed to decipher the complexity of T. gondii regulated spectrum of miRNAs to derive a set of core miRNAs central to different strains of T. gondii infection in diverse human cell lines.

Methods: We first assembled miRNAs hat are regulated by T. gondii altered across the various assortment of infections and time points of T. gondii infection in multiple cell types. For these assembled datasets, we employed specific criteria to filter the core miRNAs regulated by T. gondii. Subsequently, accounting for the spectrum of miRNA-mRNA target combinations, we applied a novel confidence criterion to extract their core experimentally-validated mRNA targets in human cell systems.

Results: This analysis resulted in the extraction of 74 core differentially regulated miRNAs and their 319 high-confidence mRNA targets. Based on these core miRNA-mRNA pairs, we derived the central biological processes perturbed by T. gondii in diverse human cell systems. Further, our analysis also resulted in the identification of novel autocrine/paracrine signalling factors that could be associated with host response modulated by T. gondii.

Conclusion: The current analysis derived a set of core miRNAs, their targets, and associated biological processes fine-tuned by T. gondii for its survival within the invaded cells.

背景:刚地弓形虫(T. gondii)是一种细胞内人畜共患原生动物寄生虫,已知可有效调节宿主系统以维持其生存。多项研究报道了不同弓形虫菌株在不同类型的宿主细胞/组织/器官中调控的大量microRNAs (miRNAs)。目的:我们旨在破译弓形虫调节的miRNAs谱的复杂性,以获得一组核心miRNAs,这些miRNAs在不同的人类细胞系中对不同的弓形虫感染菌株至关重要。方法:我们首先组装了受弓形虫调控的miRNAs,这些miRNAs在多种细胞类型的弓形虫感染的不同分类和时间点上发生了改变。对于这些组装的数据集,我们采用特定的标准来筛选弓形虫调节的核心mirna。随后,考虑到miRNA-mRNA靶标组合的光谱,我们应用了一种新的置信度标准来提取它们在人类细胞系统中经过实验验证的核心mRNA靶标。结果:该分析结果提取了74个核心差异调节mirna及其319个高置信度mRNA靶点。基于这些核心miRNA-mRNA对,我们推导了弓形虫在不同人类细胞系统中扰动的中心生物学过程。此外,我们的分析还发现了新的自分泌/旁分泌信号因子,这些因子可能与弓形虫调节的宿主反应有关。结论:目前的分析得出了一组核心mirna、它们的靶点和相关的生物学过程,这些过程被弓形虫微调,以使其在入侵细胞内存活。
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引用次数: 5
The Use of Machine Learning in MicroRNA Diagnostics: Current Perspectives. 机器学习在MicroRNA诊断中的应用:当前观点。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220818145553
Chrysanthos D Christou, Angelos C Mitsas, Ioannis Vlachavas, Georgios Tsoulfas

MicroRNAs constitute small non-coding RNAs that play a pivotal role in regulating the translation and degradation of mRNA and have been associated with many diseases. Artificial Intelligence (AI) is an evolving cluster of interrelated fields, with machine learning (ML) standing out as one of the most prominent AI fields, with a plethora of applications in almost every aspect of human life. ML could be defined as computer algorithms that learn from past data to predict future data. This review comprehensively reviews the current applications of microRNA-based ML models in healthcare. The majority of the identified studies investigated the role of microRNA-based ML models in the management of cancer and specifically gastric cancer (maximum diagnostic accuracy (Accmax): 94%), pancreatic cancer (Accmax: 93%), colorectal cancer (Accmax: 100%), breast cancer (Accmax: 97%), ovarian cancer, neck squamous cell carcinoma, liver cancer, lung cancer (Accmax: 100%), and melanoma. Except for cancer, microRNA-based ML models have been applied for a plethora of other diseases, including ulcerative colitis (Accmax: 92.8%), endometriosis, gestational diabetes mellitus (Accmax: 86%), hearing loss, ischemic stroke, coronary heart disease (Accmax: 96%), tuberculosis, pulmonary arterial hypertension (Accmax: 83%), dementia (Accmax: 82.9%), major cardiovascular events in end-stage renal disease patients, and alcohol dependence (Accmax: 79.1%). Our findings suggest that the development of microRNA-based ML models could be used to enhance the diagnostic accuracy of a plethora of diseases while at the same time substituting or minimizing the use of more invasive diagnostic means (such as endoscopy). Even not as fast as anticipated, AI will eventually infiltrate the entire healthcare industry. AI is the key to a clinical practice where medicine's inherent complexity is embraced. Therefore, AI will become a reality that physicians should conform with to avoid becoming obsolete.

MicroRNAs是一种小的非编码rna,在调节mRNA的翻译和降解中起着关键作用,并与许多疾病有关。人工智能(AI)是一个不断发展的相互关联的领域集群,机器学习(ML)作为最突出的人工智能领域之一脱颖而出,在人类生活的几乎每个方面都有大量的应用。机器学习可以被定义为从过去的数据中学习以预测未来数据的计算机算法。本文综述了目前基于microrna的ML模型在医疗保健中的应用。大多数已确定的研究调查了基于microrna的ML模型在癌症管理中的作用,特别是胃癌(最大诊断准确率(Accmax): 94%)、胰腺癌(Accmax: 93%)、结直肠癌(Accmax: 100%)、乳腺癌(Accmax: 97%)、卵巢癌、颈部鳞状细胞癌、肝癌、肺癌(Accmax: 100%)和黑色素瘤。除癌症外,基于microrna的ML模型已应用于大量其他疾病,包括溃疡性结肠炎(Accmax: 92.8%)、子宫内膜异位症、妊娠糖尿病(Accmax: 86%)、听力损失、缺血性中风、冠心病(Accmax: 96%)、结核病、肺动脉高压(Accmax: 83%)、痴呆(Accmax: 82.9%)、终末期肾病患者的主要心血管事件和酒精依赖(Accmax: 79.1%)。我们的研究结果表明,基于microrna的ML模型的开发可用于提高多种疾病的诊断准确性,同时替代或尽量减少使用更具侵入性的诊断手段(如内窥镜检查)。即使没有预期的那么快,人工智能最终也会渗透到整个医疗行业。人工智能是接受医学固有复杂性的临床实践的关键。因此,人工智能将成为一种现实,医生应该顺应,以避免被淘汰。
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引用次数: 2
Tiny Regulators in Viral Infection: Carving SARS-CoV-2 by miRNAs. 病毒感染中的微小调节因子:通过mirna雕刻SARS-CoV-2。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220816124650
Natalia Martínez-Acuña, Sonia Amelia Lozano-Sepúlveda, María Del Carmen Martínez-Guzmán, Ana María Rivas-Estilla

Viruses are microscopic biological entities that can cause diseases. Viruses require a host cell to replicate and generate progeny. Once inside, viruses hijack the main cellular machinery for their benefit, disrupting cell functions and causing detrimental effects on cell physiology. MicroRNAs are short, non-coding RNAs that regulate gene expression. Recent works have shown that cell-miRNAs can modulate antiviral defense during viral infection, and viruses can disrupt these existing miRNA networks. Furthermore, multiple RNA viruses encode their own miRNAs to evade the host immune response. In this review, we analyze the activities of both, miRNAs as pro-viral modulators and miRNAs as anti-viral agents and their relationship with the development of the disease.

病毒是可以引起疾病的微观生物实体。病毒需要宿主细胞进行复制并产生后代。一旦进入体内,病毒就会劫持主要的细胞机制,破坏细胞功能,对细胞生理造成有害影响。MicroRNAs是一种短的非编码rna,用于调节基因表达。最近的研究表明,细胞miRNA可以在病毒感染期间调节抗病毒防御,而病毒可以破坏这些现有的miRNA网络。此外,多种RNA病毒通过编码自身的mirna来逃避宿主的免疫反应。在这篇综述中,我们分析了miRNAs作为前病毒调节剂和miRNAs作为抗病毒药物的活性及其与疾病发展的关系。
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引用次数: 0
期刊
MicroRNA (Shariqah, United Arab Emirates)
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