Nucleosides, Nucleotides & Nucleic Acids最新文献

{"title":"Aptamer-directed siRNA delivery systems for triple-negative breast cancer therapy.","authors":"Dilpreet Singh, Satvir Singh, Nitin Tandon","doi":"10.1080/15257770.2025.2524468","DOIUrl":"https://doi.org/10.1080/15257770.2025.2524468","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors, making it unresponsive to targeted hormonal and HER2-based therapies. Current treatment options, including chemotherapy and radiation, have limited efficacy and are associated with severe side effects, emphasizing the need for innovative therapeutic strategies. Aptamer-siRNA conjugates have emerged as a promising gene-silencing approach, leveraging the high specificity of nucleic acid aptamers to selectively deliver short interfering RNA (siRNA) to TNBC cells. Aptamers, single-stranded DNA or RNA molecules generated <i>via</i> SELEX, exhibit nanomolar-range binding affinities (Kd ∼0.5-2.5 nM) for TNBC biomarkers such as EGFR, EpCAM, nucleolin, and MUC1, enabling receptor-mediated internalization of siRNA. Preclinical studies have demonstrated that aptamer-siRNA conjugates enhance cellular uptake by 5-10-fold, improve gene silencing efficiency (80-95%), and extend siRNA stability in circulation (from <2 h to 6-9 h). In xenograft models, aptamer-siRNA therapies have shown tumor volume reductions of 60-85%, outperforming non-targeted siRNA and chemotherapy. However, challenges such as nuclease degradation, immune responses, endosomal escape, and large-scale production remain significant hurdles to clinical translation. Recent advances in chemical modifications, lipid-based carriers, and artificial intelligence-driven aptamer design are addressing these limitations, paving the way for personalized, precision RNAi-based therapeutics. This review explores the mechanisms, recent advancements, challenges, and future directions of aptamer-siRNA therapeutics, providing a comprehensive analysis of their potential to revolutionize TNBC treatment by offering targeted, effective, and less toxic gene-silencing approaches.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-19"},"PeriodicalIF":1.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct regulation mechanism of immune-related genes in left-sided and right-sided colon cancer.","authors":"Tianfei Yi, Qi Liao, Zhiqin Jiang","doi":"10.1080/15257770.2025.2521554","DOIUrl":"https://doi.org/10.1080/15257770.2025.2521554","url":null,"abstract":"<p><p>Colon cancer is one of the most common cancers in worldwide. Emerging evidence has demonstrated distinct patterns of immune infiltration between left colon cancer (LCC) and right colon cancer (RCC), classified according to primary tumor location. However, the underlying mechanism was still unknown. Here, we identified 111 more up-regulated genes (MURGs) including <i>PD1</i> (<i>PDCD1</i>) and <i>CTLA4</i> in RCC and 166 more down-regulated genes (MDRGs) in LCC, all participating in immune-related biological processes. Notably, <i>CD83</i>, <i>CXCR4</i> and <i>ISL1</i> emerged as reversely regulated immune-related genes (IRGs) showing opposite regulation patterns between the two cancer types. Through regulatory network analysis, we found that genetic mutations predominantly drive enhanced immune infiltration in RCC through IRG up-regulation, whereas DNA methylation-mediated IRG suppression accounts for diminished immune responses in LCC. Furthermore, prognostic models based on these IRGs with high-quality were constructed in LCC and RCC respectively. In conclusion, our results provide crucial insights into the divergent immunoregulatory mechanisms governing LCC and RCC, potentially facilitating the discovery of novel biomarkers for prognosis prediction and targeted therapy.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-28"},"PeriodicalIF":1.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A positive correlation between the pseudorotational phase angle <i>P</i> and the δ_H torsion angle (H4'-C4'-C3'-H3') in nucleosides and nucleic acids.","authors":"Jesse Vanloon, Alexander Y Yan, Hongbin Yan","doi":"10.1080/15257770.2025.2516597","DOIUrl":"https://doi.org/10.1080/15257770.2025.2516597","url":null,"abstract":"<p><p>Examination of structures of DNA duplexes (A-, B-, and Z-DNA) showed a positive correlation between the pseudorotational phase angle <i>P</i> and the torsion angle δ_H (H4'-C4'-C3'-H3'). Such a <i>P</i> - δ_H plot reflects the structural features of the three types of DNA duplexes. Since the δ_H torsion angle can be measured by nuclear magnetic resonance, the linear correlation between <i>P</i> and δ_H provides a useful method for predicting the sugar pucker of nucleosides and nucleic acids.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-10"},"PeriodicalIF":1.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-regulation of miRNA and lncRNA on immunosuppression gene: unveiling the regulatory networks in cancer.","authors":"A G Dharini, Priyatharcini Kejamurthy, K T Ramya Devi","doi":"10.1080/15257770.2025.2514129","DOIUrl":"https://doi.org/10.1080/15257770.2025.2514129","url":null,"abstract":"<p><p>Cancer cells often evade immune detection and destruction by inducing immune suppression genes, which include CTLA-4, TGF-β, and PD-L1, that inhibit immune responses and promote tumour progression. Recent studies have highlighted the significance of non-coding RNAs, particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in regulating these immune suppression pathways. miRNAs, short RNA molecules that target mRNA of immune genes at the post-transcription level and influence gene expression. Similarly, lncRNAs, which act as molecular scaffolds, sponges, or regulators of gene expression, are involved in modulating immune responses by interacting with miRNAs or directly binding to immune-related genes. This review explores the complex interplay between miRNAs, lncRNAs, and immune suppression genes, detailing how these non-coding RNAs contribute to immune evasion in cancer. Furthermore, the therapeutic potential of targeting these regulatory networks is examined, highlighting current strategies and challenges in using miRNA and lncRNA modulators to enhance anti-tumour immunity. Understanding these intricate regulatory networks offers new insights into the mechanisms of immune suppression in cancer and opens avenues for developing novel therapeutic interventions to restore immune surveillance and improve the efficacy of cancer immunotherapies.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-30"},"PeriodicalIF":1.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aptamers as therapeutic targets: prospects and progress in the treatment of cancers.","authors":"Yash Sansare, Priyatharcini Kejamurthy, Suramya Singh, Aryan Ayush, Koustubhi Khani, K T Ramya Devi","doi":"10.1080/15257770.2025.2512853","DOIUrl":"https://doi.org/10.1080/15257770.2025.2512853","url":null,"abstract":"<p><p>Contemporary cancer treatments encompass diverse strategies like surgery, chemotherapy, radiation, immunotherapy, and targeted therapies, aiming for effective cancer cell control with minimal impact on healthy tissues. Aptamers are short nucleotide sequences typically containing 25-80 bases and can attach to specific target molecules as effectively as monoclonal antibodies. While the FDA has yet to approve any aptamers for oncology applications, a few, such as Pegaptanib (Macugen), have been approved for ophthalmologic conditions like age-related macular degeneration. Pegaptanib and Izervay are the approved aptamers against age-related macular degeneration (AMD) that target vascular endothelial growth factor (VEGF) and block complement component protein C5, respectively. A new type of highly sensitive and specific biosensor has recently been created to detect leukaemia cancer cells. Aptamosomes, encapsulating drugs like doxorubicin, effectively reduce tumour size and are highly advantageous over targeted drug delivery. Many aptamers have been generated against ERα, Epithelial cell adhesion molecule, EGFR, B subunit of platelet-derived growth factor, Vimentin, Osteopontin, Type II membrane protein PSMA, MUC-1, AXL receptor tyrosine kinase, CD28 agonistic aptamer, as well as for the B7-CD28 interaction, etc. This review suggests the pros and cons of aptamer usage and its advantages over antibody treatment. It also outlines the roles of aptamers and connects their modes of action with specific cancer types. The content is highly detailed, providing a comprehensive understanding of aptamer therapy and its applications.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-39"},"PeriodicalIF":1.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the interactions of Axitinib, a tyrosine kinase inhibitor, with DNA: experimental studies, molecular docking, and molecular dynamics simulations.","authors":"Pelin Şenel, Abdullah Al Faysal, Soykan Agar, Mine Yurtsever, Ayşegül Gölcü","doi":"10.1080/15257770.2025.2509977","DOIUrl":"https://doi.org/10.1080/15257770.2025.2509977","url":null,"abstract":"<p><p>Axitinib is an oral medication classified as a second-generation tyrosine kinase inhibitor. It serves as a primary treatment for metastatic renal cell carcinoma (RCC) due to its strong affinity for DNA, which leads to the disruption of the double helix structure. This disruption ultimately halts the cell cycle and induces senescence and mitotic catastrophe in RCC cells. Consequently, investigating the mechanism by which Axitinib binds to DNA is essential for comprehending its pharmacodynamic properties and for the advancement of more effective DNA-binding therapeutics. The present study aimed to examine the interaction between Axitinib and DNA through various analytical techniques, including UV-Vis spectroscopy, thermal denaturation assays, electrochemical methods, and fluorescence emission spectroscopy. According to the electrochemical studies, the binding constant (<i>K_b</i>) for Axitinib was calculated to be (5.13 ± 0.28) × 10⁴, suggesting the potential for groove binding. This finding was further supported by in-silico analyses, where molecular docking and molecular dynamics simulations indicated that the drug selectively binds to the DNA minor groove through partial intercalation, forming new hydrogen bonds with its functional groups while separating the guanine and cytosine base pairs.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-24"},"PeriodicalIF":1.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biophysical and electrochemical studies on the interaction of arbutin drug with calf-thymus DNA.","authors":"D S Bhuvaneshwari, Kandasamy Pavithra, Kuppanagounder P Elango","doi":"10.1080/15257770.2025.2512857","DOIUrl":"https://doi.org/10.1080/15257770.2025.2512857","url":null,"abstract":"<p><p>Understanding the interaction of therapeutic drugs with DNA is crucial for designing highly selective DNA-targeted medicines that could overcome the current therapeutic limitations. In this endeavour, the DNA binding behaviour of arbutin (<b>ATN</b>) was explored using multi-spectroscopic, electrochemical and computational studies. The UV-Vis spectral studies authenticated the complexation of <b>ATN</b> with CT-DNA and exposed <b>ATN</b> as a moderately strong DNA binder with a binding constant of 8.029 × 10³ M^-1. The findings of fluorescence spectral studies not only revealed the spontaneous ground state complex formation between <b>ATN</b> and CT-DNA, but also emphasised the role of hydrogen bonding and Van der Waals interactions in stabilising the <b>ATN</b>/CT-DNA complex. Since the competitive dye displacement assay strongly excluded the plausibility of classical intercalation and conventional groove binding mode of <b>ATN</b>, viscosity studies provided clues regarding the external binding mode of <b>ATN</b>. The appreciable enhancement resulted in the fluorescence emission of the <b>ATN</b>/CT-DNA complex upon increasing NaCl concentration, which certified <b>ATN</b> as an external binder. The CD spectral results exposed the <b>ATN</b>-induced moderate conformational alterations in CT-DNA. Remarkably, the voltammetric titration results labelled the glucopyranoside moiety of <b>ATN</b> as a DNA binding unit with a formation constant of 2.57 × 10⁴ M^-1 rather than the hydroquinone moiety of <b>ATN</b>. Molecular docking and metadynamics simulation outcomes served as pictorial evidence of experimental results. They revealed the predominant contribution of hydrogen bonding interactions in stabilising <b>ATN</b>/DNA complexation.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-23"},"PeriodicalIF":1.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of miRNA134 in pathogenesis and treatment of intractable epilepsy: a review article.","authors":"Maniya Kasaiyan, Mohsen Basiri, Sara Pajouhanfar","doi":"10.1080/15257770.2024.2331046","DOIUrl":"10.1080/15257770.2024.2331046","url":null,"abstract":"<p><p>MicroRNA-134 (miRNA134) has emerged as a critical regulator in the pathogenesis of epilepsy, particularly in intractable cases resistant to conventional therapies. This review explores the multifaceted roles of miRNA134 in epileptogenesis, focusing on its influence on dendritic spine morphology and synaptic plasticity. Through its interactions with proteins such as LIM kinase 1 (LIMK1), Pumilio 2 (PUM2), and Tubby-like protein 1 (TULP1), miRNA134 modulates various molecular pathways implicated in epilepsy development. Preclinical studies have shown pro-mising results in targeting miRNA134 for mitigating seizure activity, highlighting its potential as a therapeutic target. Furthermore, miRNA134 holds promise as a biomarker for epilepsy diagnosis and prognosis, offering opportunities for personalized treatment approaches. However, further research is warranted to elucidate the precise mechanisms underlying miRNA134's effects and to translate these findings into clinical applications.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"222-237"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular diversity of <i>Klebsiella pneumoniae</i> clinical isolates: antimicrobial resistance, virulence, and biofilm formation.","authors":"Ayşe Hümeyra Taşkın Kafa, Rukiye Aslan, Sevgi Durna Daştan, Cem Çeli K, Mürşit Hasbek, Ayşenur Emi Noğlu","doi":"10.1080/15257770.2024.2344741","DOIUrl":"10.1080/15257770.2024.2344741","url":null,"abstract":"<p><p>One of the mechanisms responsible for antibiotic resistance in <i>Klebsiella pneumoniae</i> is the enzymes produced by the bacteria; another important mechanism is the ability to form biofilm. In this study, antibiotic resistance, genes associated with virulence, and biofilm-forming properties of <i>K. pneumoniae</i> strains were investigated. A total of 100  <i>K. pneumoniae</i> isolates were obtained from different clinical samples identified by Matrix-Assisted Laser Desorption/Ionization time-of-flight Mass Spectrometry. Antimicrobial susceptibility testing was performed with the Phoenix 100 apparatus. The biofilm forming properties of strains were determined by the microtiter plate method. For molecular analysis, genes encoding the carbapenemase enzyme (<i>bla</i>_OXA-48, <i>bla</i>_NDM-1, <i>bla</i>_IMP, and <i>bla</i>_VIM) and biofilm-related genes (<i>tre</i>C, <i>lux</i>S, <i>mrk</i>A, and <i>wza</i>) were investigated by polymerase chain reaction (PCR). While 76% of clinical isolates were resistant to three or more antimicrobials, 24% were classified as non-multidrug resistant (non-MDR). When biofilm-forming capacities of clinical isolates were tested, it was determined that the resistant-isolates produced 59.2% strong biofilm, and susceptible-isolates produced 12.5% strong biofilm. According to PCR results, carbapenemase genes were determined as follows: <i>bla</i>_OXA-48-70%, <i>bla</i>_NDM-49%, and <i>bla</i>_KPC-19%, <i>bla</i>_OXA-48/<i>bla</i>_NDM/<i>bla</i>_KPC-12%, <i>bla</i>_OXA-48/<i>bla</i>_NDM-26%, and <i>bla</i>_OXA-48/<i>bla</i>_KPC-4%. The biofilm-associated genes in bacterial isolates were determined as follows: <i>lux</i>S-98%, <i>tre</i>C-94%, <i>mrk</i>A-88%, and <i>wza</i>-15%. In addition, Hierarchical Clustering Tree and Heatmap analysis revealed an association between isolates that lacks resistance genes and isolates lacks biofilm-formation related genes that were included in MDR or non-MDR classes. As a result, biofilm should be considered in the treatment of MDR infections, and therapy should be planned accordingly. In addition, pursuing the data and genes of antibiotic resistance is significant for combating resistance.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"361-377"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of lung adenocarcinoma subtypes based on mitochondrial energy metabolism-related genes.","authors":"Jianyang Ding, Keng Chen, Xuhui Wu","doi":"10.1080/15257770.2024.2369093","DOIUrl":"10.1080/15257770.2024.2369093","url":null,"abstract":"<p><strong>Background: </strong>Identifying subtypes of lung adenocarcinoma (LUAD) patients based on mitochondrial energy metabolism and immunotherapy sensitivity is essential for precision cancer treatment.</p><p><strong>Methods: </strong>LUAD subtypes were identified using unsupervised consensus clustering, and results were subjected to immune and tumor mutation analyses. DEGs between subtypes were identified by differential analysis. Functional enrichment and PPI network analyses were conducted. Patients were classified into high and low expression groups based on the expression of the top 10 hub genes, and survival analysis was performed. Drugs sensitive to feature genes were screened based on the correlation between hub gene expression and drug IC₅₀ value. qRT-PCR and western blot were used for gene expression detection, and CCK-8 and flow cytometry were for cell viability and apoptosis analysis.</p><p><strong>Results: </strong>Cluster-1 had significantly higher overall survival and a higher degree of immunoinfiltration and immunophenotypic score, but a lower TIDE score, DEPTH score, and TMB. Enrichment analysis showed that pathways and functions of DEGs between two clusters were mainly related to the interaction of receptor ligands with intracellular proteases. High expression of hub genes corresponded to lower patient survival rates. The predicted drugs with high sensitivity to feature genes were CDK1: Ribavirin (0.476), CCNB2: Hydroxyurea (0.474), Chelerythrine (0.470), and KIF11: Ribavirin (0.471). KIF11 and CCNB2 were highly expressed in LUAD cells and promoted cell viability and inhibited cell apoptosis.</p><p><strong>Conclusion: </strong>This study identified two subtypes of LUAD, with cluster-1 being more suitable for immunotherapy. These results provided a reference for the development of precision immunotherapy for LUAD patients.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"568-586"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}