RNA stability

RNA 稳定性
  • 文章类型: Journal Article
    癌症是一种严重威胁人类健康的疾病,其发生和发展涉及复杂的分子机制。长链非编码RNA(lncRNAs)和RNA结合蛋白(RBP)是细胞内重要的调控分子。近年来在癌症研究中引起了广泛关注。lncRNAs和RBPs的结合在mRNA的转录后调控中起着至关重要的作用,通过调节mRNA的稳定性来影响与癌症相关的蛋白质的合成。这个,反过来,调节肿瘤细胞的恶性生物学行为,如增殖和转移,并在治疗抗性中起重要作用。本研究综述了lncRNA-RBP相互作用在多种恶性肿瘤mRNA稳定性调节中的作用。重点关注这种调控相互作用的分子机制。本综述旨在更深入地了解这些分子机制,为癌症的精准治疗提供新的策略和见解。
    Cancer is a disease that poses a serious threat to human health, the occurrence and development of which involves complex molecular mechanisms. Long non‑coding RNAs (lncRNAs) and RNA‑binding proteins (RBPs) are important regulatory molecules within cells, which have garnered extensive attention in cancer research in recent years. The binding of lncRNAs and RBPs plays a crucial role in the post‑transcriptional regulation of mRNA, affecting the synthesis of proteins related to cancer by regulating the stability of mRNA. This, in turn, regulates the malignant biological behaviors of tumor cells, such as proliferation and metastasis, and serves an important role in therapeutic resistance. The present study reviewed the role of lncRNA‑RBP interactions in the regulation of mRNA stability in various malignant tumors, with a focus on the molecular mechanisms underlying this regulatory interaction. The aim of the present review was to gain a deeper understanding of these molecular mechanisms to provide new strategies and insights for the precise treatment of cancer.
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  • 文章类型: Journal Article
    尽管死后间隔估计仍然是法医学的主要目标之一,最常用的方法仍然有几个限制:出于这个原因,即使在今天,精确估计死后间隔仍然是法医病理学领域最重要的挑战之一。为了克服这些限制,近年来,已经对mRNA降解时间的潜在用途进行了大量研究,以达到更精确的验尸间隔(PMI)估计。已对文献进行了基于证据的系统综述,以评估关注mRNA降解与PMI估计之间潜在相关性的最新知识。这项研究是使用电子数据库PubMed和Scopus进行的。所进行的分析使得有可能证实mRNA对于达到更精确的PMI估计的潜在适用性。对结果的分析强调了一些mRNA的有用性,如β-肌动蛋白和甘油醛-3-磷酸脱氢酶(GAPDH)mRNA,尤其是在短时间内,在死亡的几个小时或几天内。还分析了进行这些分析的矩阵,从而减少了对外部环境的暴露,包括心脏,大脑,和牙髓。还报告了主要限制,包括大多数文章中分析的短时间间隔,缺乏数学模型,以及未能报告mRNA降解时间与PMI之间的错误率。鉴于发表的文章数量仍然很少,缺乏全球公认的标准化方法,以及用于评估mRNA降解时间的众多技术,许多和更大的研究仍然是必要的,以达到更坚实和共享的证据。
    Although the postmortem interval estimation still represents one of the main goals of forensic medicine, there are still several limitations that weigh on the methods most used for its determination: for this reason, even today, precisely estimating the postmortem interval remains one of the most important challenges in the forensic pathology field. To try to overcome these limitations, in recent years, numerous studies have been conducted on the potential use of the mRNA degradation time for reaching a more precise post mortem interval (PMI) estimation. An evidence-based systematic review of the literature has been conducted to evaluate the state of the art of the knowledge focusing on the potential correlation between mRNA degradation and PMI estimation. The research has been performed using the electronic databases PubMed and Scopus. The analysis conducted made it possible to confirm the potential applicability of mRNA for reaching a more precise PMI estimation. The analysis of the results highlighted the usefulness of some mRNAs, such as β-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, especially in short time frames, within a few hours or days of death. The matrices on which these analyses were conducted were also analyzed, resulting in less exposure to the external environment, including the heart, brain, and dental pulp. The major limitations were also reported, including the short time intervals analyzed in most of the articles, the lack of mathematical models, and the failure to report the error rate between the mRNA degradation time and PMI. Given the still small number of published articles, the lack of globally recognized standardized methods, and the numerous techniques used to evaluate the mRNA degradation times, numerous and larger studies are still necessary to reach more solid and shared evidence.
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  • 文章类型: Journal Article
    信使RNA(mRNA)在管理和预防癌症等各种疾病方面获得了极大的关注,老年痴呆症,传染病,等。由于基于COVID-19mRNA的疫苗的快速开发和成功,mRNA最近显著增长。许多产品正在临床试验中,有些产品已经获得FDA批准。然而,在优化稳定性和交付方面仍然有所改善,降低免疫原性,提高效率,扩大治疗应用,可扩展性和制造,需要长期的安全监测。通过纳米载体系统递送mRNA为管理慢性和复杂病症提供了协同结果。修饰的纳米载体负载的mRNA作为治疗策略具有极好的潜力。这个新兴平台涵盖了广泛的疾病,最近,一些临床研究正在进行中,每年都有大量出版物出版。尽管如此,许多无法解释的身体,生物,和mRNA的技术问题,更安全的人类消费。这些并发症用各种纳米载体制剂解决。本文系统地总结了基于纳米载体的mRNA递送所解决的问题和应用。修饰的纳米载体mRNA有意义地提高了mRNA稳定性并减少了其免疫原性问题。此外,讨论了几种策略,这些策略可能是将来管理复杂疾病的有效解决方案。
    Messenger RNA (mRNA) has gained marvelous attention for managing and preventing various conditions like cancer, Alzheimer\'s, infectious diseases, etc. Due to the quick development and success of the COVID-19 mRNA-based vaccines, mRNA has recently grown in prominence. A lot of products are in clinical trials and some are already FDA-approved. However, still improvements in line of optimizing stability and delivery, reducing immunogenicity, increasing efficiency, expanding therapeutic applications, scalability and manufacturing, and long-term safety monitoring are needed. The delivery of mRNA via a nanocarrier system gives a synergistic outcome for managing chronic and complicated conditions. The modified nanocarrier-loaded mRNA has excellent potential as a therapeutic strategy. This emerging platform covers a wide range of diseases, recently, several clinical studies are ongoing and numerous publications are coming out every year. Still, many unexplained physical, biological, and technical problems of mRNA for safer human consumption. These complications were addressed with various nanocarrier formulations. This review systematically summarizes the solved problems and applications of nanocarrier-based mRNA delivery. The modified nanocarrier mRNA meaningfully improved mRNA stability and abridged its immunogenicity issues. Furthermore, several strategies were discussed that can be an effective solution in the future for managing complicated diseases.
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  • 文章类型: Systematic Review
    法医学中的死后间隔(PMI)对于刑事和民事案件都极为重要,并推荐了几种技术。这篇系统综述只关注与RNA分析相关的方法,而不是包括所有建议的PMI确定方法。术语PMI将在本审查中用于表示一个人的死亡和尸体的尸检之间的时间。在进行本系统评价时,我们遵守了系统评价和荟萃分析(PRISMA)指南的首选报告项目。在各种温度下,在各种时间间隔对各种组织的研究大多数是非人类的,只有一小部分人在人类身上。然后使用各种统计方法提供结果。要计算PMI,使用几种组织检查死后RNA降解。如此获得的结果具有相反的极性。虽然一些研究表明,各种组织中的RNA稳定性在死亡后几天保持不变,另一组研究显示,随着死亡时间的推移,RNA会明显降解,这受温度和其他因素的影响很大。这些因素对RNA降解前后因素的多参数数学模型有影响,以及其适用性和可行性。在控制了难以估计法医样品中的RNA的各种因素和挑战之后,使用RNA降解来估计PMI可以证明是高度客观和有效的。
    Postmortem interval (PMI) in legal medicine is extremely important for both criminal and civil cases, and several sorts of techniques have been recommended. This systematic review solely focuses on approaches linked to RNA analysis, instead of including all proposed methods for determining the PMI. The term PMI will be used in this review to indicate the time between a person\'s death and the postmortem examination of the body. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines when conducting this systematic review. The majority of studies on various tissues at various time intervals at various temperatures are non-human, and just a small number are on humans. The results are then provided using various statistical approaches. To calculate the PMI, post-mortem RNA degradation was examined using several tissues. The result so obtained had an opposite polarity. While some studies show that RNA stability in various tissues remained constant for several days after death, the other group of studies showed evident RNA degradation over time post-mortem, which was significantly influenced by temperature and other agonal factors. These factors have an impact on the multi-parametric mathematical model of ante and post-mortem factors on RNA degradation, as well as its applicability and feasibility. The estimation of PMI using RNA degradation can prove to be highly objective and efficient after controlling for the various factors and challenges that pose the estimation of RNA in forensic samples difficult.
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  • 文章类型: Journal Article
    尽管在诊断方面取得了进展,预后,和治疗方式,心肌梗死(MI)仍然是发病和死亡的主要原因.MI后受损的细胞信号传导会导致适应不良的变化,从而导致心脏重塑。已经研究了微小RNA(miRNA/miR)以及其他分子组分在各种心脏疾病如MI的发病机理中参与细胞信号传导的情况。miRNA是负调控基因表达的非编码小RNA。它们与互补的mRNA结合并通过改变其靶向的mRNA的稳定性来调节蛋白质合成的速率。单个miRNA可以通过靶向数百个mRNA来调节几种细胞信号传导途径。这篇综述着重于MI后细胞和循环(外泌体)miRNA对心脏重塑的生物发生和有益作用。特别是,详细描述了在MI后的心脏重塑中起重要作用的miR-1、-133、135和-29。还将讨论未来需要解决的限制,以进一步开发基于miRNA的心血管疾病治疗剂。
    Despite advances in diagnostic, prognostic, and treatment modalities, myocardial infarction (MI) remains a leading cause of morbidity and mortality. Impaired cellular signaling after an MI causes maladaptive changes resulting in cardiac remodeling. MicroRNAs (miRNAs/miR) along with other molecular components have been investigated for their involvement in cellular signaling in the pathogenesis of various cardiac conditions like MI. miRNAs are small non-coding RNAs that negatively regulate gene expression. They bind to complementary mRNAs and regulate the rate of protein synthesis by altering the stability of their targeted mRNAs. A single miRNA can modulate several cellular signaling pathways by targeting hundreds of mRNAs. This review focuses on the biogenesis and beneficial effects of cellular and circulating (exosomal) miRNAs on cardiac remodeling after an MI. Particularly, miR-1, -133, 135, and -29 that play an essential role in cardiac remodeling after an MI are described in detail. The limitations that will need to be addressed in the future for the further development of miRNA-based therapeutics for cardiovascular conditions will also be discussed.
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  • 文章类型: Journal Article
    尽管儿童急性淋巴细胞白血病(ALL)的生存率显着改善,无反应或复发患者仍然是儿童疾病死亡的最常见原因之一。基于遗传标记的准确患者风险分层可以提高生存率。miRNAs可以代表新的候选诊断,预测和预后潜力;然而,许多团体调查了他们的参与,结果相互矛盾。目的:通过系统评价阐明miRNAs作为生物标志物的作用。结果:从45份手稿的修订中,我们发现miR-128和miR-181过表达可以代表ALL诊断的标志物,而miR-708和miR-99a的低表达可能是不良预后的标志物.结论:这些特征可以改善患者的分类和风险分层,并改善ALL结局。
    Despite remarkable improvements in survival of childhood acute lymphoblastic leukemia (ALL), nonresponding or relapsing patients still represent one of the most frequent causes of death by disease in children. Accurate patient risk stratification based on genetic markers could increases survival rates. miRNAs can represent novel candidates with diagnostic, predictive and prognostic potential; however, many groups investigated their involvement with contradictory results. Aim: To clarify the role of miRNAs as biomarkers through a systematic review. Results: From a revision of 45 manuscripts, we found that miR-128 and miR-181 overexpression could represent markers for ALL diagnosis and underexpression of miR-708 and miR-99a could be markers for bad prognosis. Conclusion: These signatures could refine classification and risk stratification of patients and improve ALL outcome.
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  • 文章类型: Journal Article
    Post-mortem interval (PMI) determination is one of the most important issues in forensic sciences. In the past, forensic scientists provided different approaches (physical, chemical, and entomological) for the estimation of PMI without success.However, advances in molecular biology over the last two decades have allowed us to assess the time-dependent degradation of biological markers (e.g., proteins, DNA, and RNA). Thus, the aim of the manuscript is to provide a review of the recent progress in the estimation of PMI using molecular biology methods, mainly focusing on the potential usefulness of RNA markers. To this end, 29 studies have been systematically reviewed, each one chosen according to specific inclusion/exclusion criteria. The selected studies evaluated the contribution of endogenous reference genes in different biological samples in order to determine the PMI based on post-mortem RNA degradation as a function of other influencing factors such as time, cause of death, and environmental conditions.
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  • 文章类型: Journal Article
    Ras-GTPase-activating protein (SH3 domain)-binding proteins (G3BPs, also known as Rasputin) are a family of RNA binding proteins that regulate gene expression in response to environmental stresses by controlling mRNA stability and translation. G3BPs appear to facilitate this activity through their role in stress granules for which they are considered a core component, however, it should be noted that not all stress granules contain G3BPs and this appears to be contextual depending on the environmental stress and the cell type. Although the role of G3BPs in stress granules appears to be one of its major roles, data also strongly suggests that they interact with mRNAs outside of stress granules to regulate gene expression. G3BPs have been implicated in several diseases including cancer progression, invasion, and metastasis as well as virus survival. There is now a body of evidence that suggests targeting of G3BPs could be explored as a form of cancer therapeutic. This review discusses the important discoveries and advancements made in the field of G3BPs biology over the last two decades including their roles in RNA stability, translational control of cellular transcripts, stress granule formation, cancer progression and its interactions with viruses during infection. An emerging theme for G3BPs is their ability to regulate gene expression in response to environmental stimuli, disease progression and virus infection making it an intriguing target for disease therapies.
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  • 文章类型: Journal Article
    It is well recognised that genomic, proteomic and biomarker studies require properly annotated and well-characterised biospecimens. Consequently, this necessitates biobanks to collect, store and distribute biospecimens under stringent quality control and assurance measures. However, despite this realisation, there remains a lack of standardisation in quality management among biobanks and consensus as to which quality indicators provide the optimal molecular diagnostic performance tools and information for biospecimens. In an attempt to identify key factors that predict tissue specimen integrity and quality, this systematic review investigated the measures reported in the literature, which characterised the collection, processing and storage of high-quality tissue specimens. Our findings demonstrated RNA integrity, alone, may not be an effective measure of tissue quality. Furthermore, the frequently reported parameters related to biospecimen integrity, such as storage time, temperature, time to cryopreservation and tissue morphology were also not effective indicators of quality control and assurance. These findings suggest that it is unlikely that a single marker will provide the optimal diagnostic and performance information for biospecimens, but rather, a panel of markers assessing the molecular integrity of the lifespan of the biospecimen is required. Further work is needed to identify which factors predict specimen integrity and quality in biobanked tissue specimens.
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  • 文章类型: Journal Article
    BACKGROUND: HIV viral load (VL) testing is the gold standard for antiretroviral treatment monitoring, but many barriers exist to VL testing in resource-limited settings, including storage and transport limitations for whole blood and plasma. Data from various studies indicate that HIV RNA is stable beyond current recommendations. We conducted a systematic review to assess stability data of HIV RNA in whole blood and plasma across times and temperatures.
    RESULTS: Using a pre-defined protocol, five databases were searched for studies where blood samples from HIV patients were stored at time and temperature points that exceeded manufacturer recommendations. RNA stability, the primary outcome, was measured by the difference in means compared to samples stored within established thresholds. RNA stability was defined as ≤0.5 log degradation. The search identified 10,716 titles, of which nine full-text articles were included for review. HIV RNA maintained stability in EDTA whole blood and plasma at all measured time points up to 168 hours when stored at 4°C, while stability was detected at 72 hours (95% confidence) in whole blood at 25°C, with data points before and beyond 72 hours suggesting stability but not reaching statistical significance. For EDTA plasma stored at 30°C, stability was maintained up to 48 hours (95% confidence), with OLS linear regression estimates up to 127 hours, suggesting stability. Overall, quality of studies was moderate. Limitations included small sample sizes, few studies meeting inclusion criteria, and no studies examining RNA stability in low viremia (<3,000 copies/mL) environments.
    CONCLUSIONS: Whole blood and plasma samples in EDTA may remain stable under conditions exceeding current manufacturer recommendations for HIV VL testing. However, given the limited number of studies addressing this question, especially at low levels of viremia, additional evaluations on HIV RNA stability in EDTA tubes and PPT in field conditions are needed.
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