peptide nucleic acids

肽核酸
  • 文章类型: Systematic Review
    肽核酸(PNA)是合成分子,就像DNA/RNA,但是有不同的积木。它们已被研究为潜在的抗生素,因为它们可以特异性地靶向和结合mRNA并破坏目标基因的功能。本系统综述旨在对PNA作为抗菌剂的现状进行深入分析,定义有效PNA结构的特征,并解决PNA进展中的差距,成为临床合格的药物。按照PRISMA模型,我们搜索了四个电子数据库WebofScience,PubMed,SciFinder和Scopus,在1994年至2023年之间发现了627篇发表的文章。经过筛选和严格的选择过程,使用明确的纳入和排除标准,选择了65篇科学文章,包含656个最小抑制浓度(MIC)数据。针对20种细菌物种评估了PNA的抗菌活性。研究最多的革兰氏阴性和革兰氏阳性是大肠杆菌(n=266)和金黄色葡萄球菌(n=53),分别。此外,我们揭示了PNA设计的影响,如结构长度,绑定位置,和载体剂对其抗菌活性的影响。最后,我们检查了抗菌测试模型的效果,以评估PNA的抑制作用,强调差距和前景。本系统综述全面评估了PNA作为抗菌剂的潜力,并为寻求新的治疗策略来对抗抗生素抗性细菌的研究人员和临床医生提供了有价值的见解。
    Peptide nucleic acids (PNAs) are synthetic molecules that are like DNA/RNA, but with different building blocks. PNAs target and bind to mRNAs and disrupt the function of a targeted gene, hence they have been studied as potential antibacterials. The aim of this systematic review was to provide an in-depth analysis of the current status of PNAs as antibacterial agents, define the characteristics of the effective PNA constructs, and address the gap in advancing PNAs to become clinically competent agents. Following the PRISMA model, four electronic databases were searched: Web of Science, PubMed, SciFinder and Scopus. A total of 627 articles published between 1994 and 2023 were found. After screening and a rigorous selection process using explicit inclusion and exclusion criteria, 65 scientific articles were selected, containing 656 minimum inhibitory concentration (MIC) data. The antibacterial activity of PNAs was assessed against 20 bacterial species. The most studied Gram-negative and Gram-positive bacteria were Escherichia coli (n=266) and Staphylococcus aureus (n=53), respectively. In addition, the effect of PNA design, including construct length, binding location, and carrier agents, on antibacterial activity was shown. Finally, antibacterial test models to assess the inhibitory effects of PNAs were examined, emphasising gaps and prospects. This systematic review provides a comprehensive assessment of the potential of PNAs as antibacterial agents and offers valuable insights for researchers and clinicians seeking novel therapeutic strategies in the context of increasing rates of antibiotic-resistant bacteria.
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  • 文章类型: Journal Article
    肽核酸(PNA)是一种对天然DNA或RNA具有高特异性和结合亲和力的核酸模拟物,以及对酶降解的抗性。PNA序列可以被设计为选择性地沉默基因表达,这使得PNA成为抗菌应用的有前途的工具。然而,PNA的膜通透性差仍然是其在细胞中应用的主要限制因素。为了克服这个障碍,已经开发了具有不同分子的PNA缀合物。这篇小型综述侧重于PNA与细胞穿透肽的共价连接缀合物,氨基糖,氨基糖苷类抗生素,和测试过的非肽分子,主要作为PNA携带者,在抗菌和抗病毒应用。还讨论了缀合的化学性质和应用的接头。
    Peptide nucleic acid (PNA) is a nucleic acid mimic with high specificity and binding affinity to natural DNA or RNA, as well as resistance to enzymatic degradation. PNA sequences can be designed to selectively silence gene expression, which makes PNA a promising tool for antimicrobial applications. However, the poor membrane permeability of PNA remains the main limiting factor for its applications in cells. To overcome this obstacle, PNA conjugates with different molecules have been developed. This mini-review focuses on covalently linked conjugates of PNA with cell-penetrating peptides, aminosugars, aminoglycoside antibiotics, and non-peptidic molecules that were tested, primarily as PNA carriers, in antibacterial and antiviral applications. The chemistries of the conjugation and the applied linkers are also discussed.
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  • 文章类型: Review
    背景:压力和倦怠导致缺勤水平增加,地区护理中的错误和投诉。这个问题似乎正在恶化,有必要进行变革并引入新的干预措施来扭转这一趋势。专业护士辩护人(PNA)的角色在护理中相对较新,在这种情况下,他们的配合可能对地区护理有益。目的:本文旨在探讨PNA在地区护理中的潜在作用,以及将其引入社区环境是否有助于减轻压力,倦怠和旷工。方法:探索与地区护理实践领域相关的文献,并考虑为什么会发生倦怠,PNA如何工作来减少这种情况(使用A-EQUIP模型),和可能存在的障碍。结果:地区护理工作倦怠是一个严重的问题,可能会影响患者护理质量。有明确的迹象表明,PNA,如果有效使用,可以减轻压力和倦怠,从而提高出勤率,保留和患者护理质量。结论:有证据表明PNA在降低职业倦怠和改善患者护理方面具有潜在的益处。
    Background: Stress and burnout has been leading to increased levels of absences, errors and complaints in district nursing. This problem appears to be worsening, necessitating the need for change and introducing new interventions to reverse this trend. The Professional Nurse Advocate (PNA) role is relatively new within nursing and their assitance in such instances could be of benefit to district nursing. Aim: This article aims to explore the potential role of PNAs in district nursing and whether their introduction to community settings could help reduce levels of stress, burnout and absenteeism. Method: The literature is explored with relation to the field of district nursing practice and consideration is given to why burnout is occurring, how PNAs could work to reduce this (using A-EQUIP model), and barriers that could exist. Findings: Burnout in district nursing is a significant problem that can affect quality of patient care. There is clear indication that PNAs, if used effectively, could reduce stress and burnout, and consequently lead to improved attendance, retention and quality of patient care. Conclusion: There is evidence for the potential benefits of PNAs within district nursing in terms of reducing burnout and improving patient care.
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  • 文章类型: Journal Article
    OBJECTIVE: Molecular testing in non-small cell lung cancer (NSCLC) aids in identifying oncogenic alterations. The aim of this study was to compare the rates of detection of oncogenic alterations and responsiveness to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) according to EGFR mutation status as determined by peptide nucleic acid (PNA) clamping or direct sequencing (DS).
    METHODS: We performed a systematic literature search using MEDLINE, EMBASE, and the Cochrane Central Register. Data from included studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and receiver operating characteristic curves. A meta-regression analysis was conducted to identify potential sources of heterogeneity between selected studies.
    RESULTS: We identified 10 studies comprising 924 patients. Oncogenic alterations were detected in 340 of 924 cases (36.8%) with PNA clamping and in 250 of 924 (27.1%) with DS. The pooled sensitivities of PNA clamping and DS were 0.93 [95% confidence interval (CI): 0.90-0.95] and 0.69 (95% CI: 0.64-0.73), respectively. According to meta-regression analysis, none of the covariates were found to be significant sources of heterogeneity. With respect to treatment responses to EGFR-TKIs, there was no significant difference therein between EGFR mutations detected by PNA clamping and DS (53.4% vs. 50.8%; risk ratio, 0.99; 95% CI 0.83-1.19; p=0.874).
    CONCLUSIONS: We demonstrated that PNA clamping has a higher sensitivity than DS for detecting oncogenic alterations in NSCLC. Our findings suggest that PNA clamping is a more useful method for clinical practice.
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    文章类型: Journal Article
    Peptide nucleic acid (PNA) is a DNA surrogate in which the phosphate deoxyribose backbone of DNA is replaced by repeating N-(2-aminoethyl)glycine units. PNA can hybridize to the complementary DNA and RNA with higher affinity than their oligonucleotide counterparts. This character of PNA not only makes it a new tool for the studies of molecular biology but also the potential candidate for gene-targeting drugs. The non-ionic backbone of PNA leads to stable hybrids with the nucleic acids, but at the same time, the neutral backbone results in poor cellular uptake. To address this problem, studies on modified PNA progress rapidly in recent years. We reviewed literature reports combined with our study about the delivery methods, including backbone modified PNA and PNA-ligand conjugates, and the cellular uptake of modified PNA. In addition, we summarized the problems and future prospect of the cellular delivery of modified PNA.
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  • 文章类型: Journal Article
    Peptide nucleic acid (PNA) is a mimic of DNA that shows a high chemical stability and can survive the enzymatic degradation of nucleases and proteases. The superior binding properties of PNA enable the formation of PNA/DNA or PNA/RNA duplex with excellent thermal stability and unique ionic strength effect. The introduction of microarray makes it possible to achieve accurate, high throughput parallel analysis of DNA or RNA with a highly integrated and low reagents consuming device. This powerful tool expands the applications of PNA in genotyping based on single nucleotide polymorphism (SNP) detection, the monitoring of disease-related miRNA expression and pathogen detection. This review paper discusses the fabrications of PNA microarrays through in situ synthesis strategy or spotting method by automatic devices, the various detection methods for the microarray-based hybridization and the current applications of PNA microarrays.
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  • 文章类型: Journal Article
    BACKGROUND: DNA/RNA-based drugs are considered of major interest in molecular diagnosis and nonviral gene therapy. In this field, peptide nucleic acids (PNAs, DNA analogs in which the sugar-phosphate backbone is replaced by N-(2-aminoethyl)glycine units or similar building blocks) have been demonstrated to be excellent candidates as diagnostic reagents and biodrugs.
    METHODS: Recent (2002 - 2013) patents based on studies on development of PNA analogs, delivery systems for PNAs, applications of PNAs in molecular diagnosis, and use of PNA for innovative therapeutic protocols.
    CONCLUSIONS: PNAs are unique reagents in molecular diagnosis and have been proven to be very active and specific for alteration of gene expression, despite the fact that solubility and uptake by target cells can be limiting factors. Accordingly, patents on PNAs have taken in great consideration delivery strategies. PNAs have been proven stable and effective in vivo, despite the fact that possible long-term toxicity should be considered. For possible clinical applications, the use of PNA molecules in combination with drugs already employed in therapy has been suggested. Considering the patents available and the results on in vivo testing on animal models, we expect in the near future relevant PNA-based clinical trials.
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  • 文章类型: Journal Article
    Fungal infections are a frequent occurrence in medical practice due to increasing numbers of immunosuppressed patients. New antifungal medications have been developed and it has become evident that different fungi require different treatments as some are intrinsically resistant to these drugs. Thus, it is imperative that pathologists recognize the limitations of histopathologic diagnosis regarding speciation of fungal infections and advocate for the use of different techniques that can help define the genus and species of the fungus present in the specimen they are studying. In this review we present the use of in situ hybridization as an important adjunct for the diagnosis of fungal diseases, the different techniques that have been used for fungal identification, and the limitations that these techniques have.
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  • 文章类型: Journal Article
    Peptide nucleic acids (PNAs) are polyamidic oligonucleotide analogues which have been described for the first time almost twenty years ago and were immediately found to be excellent tool in binding DNA and RNA for diagnostics and gene regulation. Their use as therapeutic agents have been proposed since early studies and recent advancements in cellular delivery systems and in the so called anti-gene strategy make them good candidates for drug development. The search for new chemical modification of PNAs is a very active field of research and new structures are continuously proposed. This review focuses on the modification of the PNA backbone, and their possible use in medicinal chemistry with an update of this topics in view of emerging new trends and opening of new possibilities In particular two classes of structurally biased PNAs are described in details: i) PNAs with acyclic structures and their helical preference, which is regulated by stereochemistry and ii) cyclic PNAs with preorganized structures, whose performances depend both on stereochemistry and on conformational constraints. The properties of these compounds are discussed in terms of affinity for nucleic acids, and several examples of their use in cellular or animal systems are presented , with exciting new fields of research such as microRNA (miR) targeting and gene repair.
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  • DOI:
    文章类型: Journal Article
    Peptide nucleic acids (PNAs) are synthetic analogs of DNA that hybridize with complementary DNAs or RNAs with high affinity and specificity, essentially because of an uncharged and flexible polyamide backbone. Originally conceived as ligand for the recognition of double stranded DNA, the unique physico-chemical properties of PNAs have led to the development of a variety of research and diagnostic assays. Initially used as antisense and antigene reagents, the more recent applications of PNA have involved their use as molecular hybridization probes. Thus, sensitive and robust PNA-dependent methods have been designed for developing anti-cancer drugs, modulating PCR reactions, detecting genomic mutation or labelling chromosomes in situ.
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