Nucleosides, Nucleotides & Nucleic Acids最新文献

This study investigates the potential of a protein-DNA aptamer conjugate to enhance aptamer binding to recombinant human intercellular adhesion molecule 1 (rhICAM-1). Aptamers are single-stranded nucleic acids that bind target molecules through hydrogen bonding and hydrophobic interactions. Conjugating aptamers with antibodies or proteins has been shown to improve their binding affinity. Using Systematic Evolution of Ligands by Exponential Enrichment (SELEX), eight rounds of selection were performed with ICAM-1-coupled Dynabeads Protein A, identifying a DI05 as having the strongest binding affinity to rhICAM-1. An antibody inhibition assay showed a significant reduction in rhICAM-1 binding to immobilized aptamers (DI05, DI20, DI31, and DI33). Additionally, the binding affinity of eGFP-conjugated DI05 to rhICAM-1 was higher than that of unconjugated DI05. Docking simulations revealed close contact between DI05 and ICAM-1, with interactions primarily mediated by hydrogen bonds within three hairpin structures at ≤2.8 Å. These findings highlight the potential of aptamer-small protein conjugates as a promising strategy to enhance aptamer binding characteristics.

The first encounter I ever had with Fritz Eckstein was in 1969 at Stanford University to discuss a polyribonucleotide in which the phosphate was replaced by thiophosphate groups, engendering increased interferon induction (i.e. antiviral activity). His research work then focused on the versatility of oligonucleotides as potential therapeutics. Spanning a period of several decades, various other leads of research were undertaken, i.e. 2'- and 3'-amino or -azido-substituted deoxyribonucleoside analogs, hammerhead ribozymes, small non-coding mRNAs (siRNAs, miRNAs) for monitoring gene therapy, and thiophosphate-substituted nucleotide analogs to be used in RNA and DNA sequencing. This exemplary scientific career generated not one but a multitude of magic bullets for biomedical research and application.

The 21^th biennial symposium on Purine and Pyrimidine metabolism (PP25) was organized by the Purine and Pyrimidine Society (PPS) in June 2025. The symposium took place in Barcelona, Spain, and the chairman was Prof. Marçal Pastor-Anglada affiliated to the University of Barcelona. The scientific program covered various topics such as inborn errors, cancer, immunity, enzymatic reactions, drug development etc. and was presented in 8 sessions over three days. The current issue of Nucleosides, Nucleotides & Nucleic Acids is a collection of articles issued from PP25-presentations and other PPS-related manuscripts, and in this editorial, we give an overview of the scientific program of the meeting.

Objective: To explore the effect of long non-coding (lnc)RNA AK094457 on the malignant biological functions of oesophageal cancer, such as proliferation, migration and invasion.

Methods: We constructed lncRNA AK094457 overexpressing and blank control oesophageal cancer Eca109 cell lines using lentivirus, and divided the cells into the Control group, the overexpression (OE)-AK094457 group and the OE-negative control (NC) group. The expression level of lncRNA AK094457 in each of the groups was detected using quantitative real-time polymerase chain reaction analysis. The proliferative capacity of cells was assessed using a cell counting kit-8 assay and colony formation assay. Cell invasion ability was detected via a Transwell invasion assay, and the migration ability of cells was detected using a wound-healing assay. The cell-cycle levels and apoptosis were detected using flow cytometry. The expression of beta (β)-catenin, a key protein in the Wnt pathway, was detected via western blot analysis.

Results: Compared with the Control group and the OE-NC group, the expression of lncRNA AK09457 in the OE-AK094457 group was significantly increased (p < 0.001). Various in-vitro experiments showed that overexpression of lncRNA AK094457 significantly inhibited the proliferation, migration and invasion of oesophageal cancer cells, stalled the cell cycle at the G0/G1 phase and promoted apoptosis of oesophageal cancer cells. Western blot results showed that the expression of β-catenin in the OE-AK094457 group was significantly lower than that in the other two groups, indicating that lncRNA AK094457 can affect the malignant biological function of oesophageal cancer cells through the Wnt pathway (p < 0.001).

Conclusions: Long non-coding RNA AK094457 can inhibit certain functions of oesophageal cancer cells, such as proliferation, migration and invasion, by activating the Wnt pathway.

Objective: This investigation sought to characterize the clinical relevance and functional impact of miR-1180-3p in breast cancer (BRCA) pathogenesis while delineating its underlying mechanistic basis.

Methods: MiR-1180-3p expression in tumor tissues from 139 BRCA patients and cells was assessed by using polymerase chain reaction (PCR). Correlation analysis evaluated its association with clinicopathological characteristics. In vitro, the functional consequences of miR-1180-3p expression on cell proliferation, migration, and invasion of MCF7 and MDA-MB-231 were determined by Cell Counting Kit-8 and Transwell assay. Bioinformatic analysis predicted miR-1180-3p target genes, with dual luciferase reporter assays validated the interaction. Rescue studies were conducted to confirm the effect of the miR-1180-3p/ZNF83 axis on BRCA cell functions.

Results: Significant miR-1180-3p downregulation was observed in BRCA. Low miR-1180-3p levels correlated with poor prognosis and shorter survival, and were associated with ultrasound features like tumor size and lymph node metastasis. Functional studies showed miR-1180-3p overexpression inhibited BRCA cell proliferation, migration, and invasion, while its downstream target gene ZNF83 exhibited significantly elevated expression levels in BRCA cells, and overexpression of ZNF83 abrogated miR-1180-3p-mediated suppression of proliferative, migratory, and invasive capacities in BRCA cells.

Conclusion: In summary, miR-1180-3p served as a prognostic biomarker for BRCA and regulated cellular functions, thereby being involved in tumor progression.

Hepatocellular carcinoma (HCC), which predominantly manifests as a malignant form of primary liver cancer, remains resistant to existing therapies in many patients. Therefore, elucidating the cellular processes and signaling networks driving HCC progression and discovering novel treatment targets remain key areas of research. ELF3-AS1, miR-98-5p, and CPSF4 are closely associated with liver cancer, but the relationship between them is unclear. ELF3-AS1, miR-98-5p, and CPSF4 levels were quantified using RT-qPCR. CPSF4 expression was analyzed through Western blotting. Liver tumor cell viability was assessed using CCK8 assays. The metastatic potential of cells was primarily evaluated using wound healing and Transwell assays. ELF3-AS1's impact on tumors was validated through live animal experiments by inducing subcutaneous tumor formation in nude mice. RNAhybrid and TargetScan analyzed potential miR-98-5p target regions in CPSF4 and ELF3-AS1. Our study demonstrates that reducing ELF3-AS1 expression can inhibit hepatoma cell proliferation, migration, and invasive abilities. Specifically, knocking down ELF3-AS1 can reduce the expression of CPSF4. Knocking down ELF3-AS1 can suppress liver cancer development in live animal models. In addition, miR-98-5p can bind ELF3-AS1 and CPSF4 and down-regulate the expression of CPSF4. In summary, ELF3-AS1 promotes the proliferation, migration, and invasion of HCC cells by inhibiting miR-98-5p/CPSF4 axis.

The synthesis, characterization, double stranded (ds-DNA) and G-quadruplex DNA (G-DNA) binding affinities of a new Pt(II) complex of a new benzimidazole based ligand 6-(1H-Imidazol-4-yl)-1,7-dihydroimidazo[4,5-f]benzimidazol-2-ol (idbo) is reported. The interactions of Pt(II) complex with ds-DNA and G-DNA have been studied by UV-Vis titration, UV thermal melting, fluorescent intercalator displacement (FID), competition dialysis and the findings were compared with the other known G-DNA binding compounds. The metal complex binds both G-DNA and ds-DNA according to UV titration results. Uv thermal melting studies show that the new Pt(II) complex stabilize G-quadruplex structure. A high G-DNA selectivity is calculated with FID results. Also, competition dialysis results prove the 1.6 selectivity on G-DNA binding of complex over ds-DNA.

Osteoarthritis (OA) is a prevalent degenerative joint disease with limited diagnostic and therapeutic options. Recent studies suggest that nucleotide metabolism (NM) plays a key role in OA progression. This study aimed to identify NM-related genes involved in OA and explore their potential mechanisms. Transcriptomic data from the GEO database were analyzed using differential expression and machine learning approaches. Two key genes, AMPD3 and TYMS, were identified and validated through ROC analysis and clinical tissue samples. A nomogram based on these genes demonstrated strong diagnostic performance. Enrichment analysis revealed their involvement in multiple pathways, including oxidative phosphorylation. Immune infiltration analysis indicated correlations with immune cells. Drug prediction identified several candidate compounds; molecular docking further confirmed strong binding affinities-AMPD3 with AM095, and TYMS with deoxyuridine monophosphate. These findings suggest that AMPD3 and TYMS are key regulators in OA-related NM and may serve as novel biomarkers and therapeutic targets.

Synchrotron radiation circular dichroism spectra of 2'-deoxyribonucleosides, as well as a few guanine nucleosides were recorded between 170-330 nm. The CD profile of each nucleoside is unique, and there is a general similarity in the SRCD patterns of deoxyribonucleosides and those recorded by a benchtop CD as previously reported. Furthermore, the locked nucleic acid derivative of guanine nucleoside (LNA-G) showed opposite CD profiles to the rest of the guanine nucleoside derivatives. The conformational parameters of the nucleosides were analyzed against the crystal structures available in the Cambridge Crystallographic Data Center. The pseudorotational phase angles of the guanine nucleoside derivatives in solution were also determined based on NMR coupling constants. Analyses showed no apparent correlation between pseudorotational phase angles and CD patterns.

Oral lichen planus (OLP) is a chronic inflammatory condition that has been clinically linked with the risk of developing oral cancer. The present study aimed to determine the oxidative stress in oral lichen planus (OLP) by assessing the immunohistochemical (IHC) expression of 8-hydroxydeoxyguanosine (8-OHdG) in OLP tissue samples and comparing it with that of normal oral mucosa. The study group consisted of 30 formalin-fixed, paraffin-embedded (FFPE) tissue blocks from oral lichen planus (OLP) cases, while 10 normal oral mucosa samples served as the control group. Tissue sections of 5-micron thickness were prepared and immunostained with the 8-hydroxydeoxyguanosine (8-OHdG) antibody. The stained slides were examined under a light microscope, and statistical analysis was conducted using Fisher's exact test. A significant increase in oxidative DNA damage marker 8-OHdG expression (p < 0.05) was observed within the basal and suprabasal epithelial layers of lichen planus tissue samples. In contrast, no immunoreactivity was detected in the normal oral mucosa. Excessive production of reactive oxygen species (ROS) during chronic inflammation is believed to play a crucial role in inducing DNA damage. The mutagenic marker 8-hydroxydeoxyguanosine (8-OHdG) in oral lichen planus tissue highlights its potential as a biomarker for assessing the risk of inflammation-driven carcinogenesis. Further research, incorporating various oxidative stress markers and clinicopathological correlations, is essential to enhance early prediction of malignant transformation in oral lichen planus.