Nucleosides, Nucleotides & Nucleic Acids最新文献

{"title":"Post-COVID increase in N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3-carboxamide (Met4PY) associates with inflammatory and endothelial activation markers.","authors":"Aleksandra Jóźwiak, Adela Lewandowska, Dominika Sawicka, Agata Jędrzejewska, Alicja Braczko, Marzena Romanowska-Kocejko, Marta Żarczyńska-Buchowiecka, Milena Deptuła, Małgorzata Zawrzykraj, Michał Pikuła, Barbara Kutryb-Zając, Marcin Hellmann, Paulina Mierzejewska","doi":"10.1080/15257770.2026.2650677","DOIUrl":"10.1080/15257770.2026.2650677","url":null,"abstract":"<p><p>COVID-19 is associated with long-term vascular complications, but the underlying mechanisms remain incompletely understood. During infection, NAD⁺ homeostasis becomes dys-regulated, with excessive NAD⁺ consumption and enhanced catabolic flux through nicotinamide methylation pathways. This imbalance leads to NAD⁺ depletion accompanied by accumulation of pyridone metabolites, including N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3-carboxamide (Met4PY). These derivatives have been linked to oxidative stress, endothelial dysfunction, and cardiovascular risk, yet their role in long COVID remains unclear. We enrolled 26 post-COVID patients with persistent cardiovascular symptoms and 8 healthy controls. Serum concentrations of Met2PY and Met4PY were quantified by LC/MS. High-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNFα), interleukin-10 (IL-10), and soluble intercellular adhesion molecule-1 (sICAM-1) were measured to assess systemic inflammation and endothelial activation. Statistical analyses included group comparisons and correlation analyses. We observed significantly elevated Met2PY levels (0.770 ± 0.08 vs. 0.389 ± 0.09 µmol/l) and a trend toward increased Met4PY (0.095 ± 0.01 vs. 0.055 ± 0.01 µmol/l) in post-COVID patients compared with controls. Both metabolites positively correlated with hsCRP. Importantly, Met2PY was associated with an unfavorable cytokine profile (higher TNFα/IL-10 ratio) and increased sICAM-1 levels, whereas no such associations were observed for Met4PY. Persistent dysregulation of NAD⁺ metabolism and accumulation of pyridone metabolites, particularly Met2PY, are associated with markers of chronic endothelial activation and inflammation in long COVID. These findings support the potential utility of Met2PY as a biomarker to identify patients at higher risk for endothelial dysfunction and cardiovascular events, enabling more personalized risk stratification and follow-up.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1132-1145"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627829","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 impact of vitamin B12 deficiency on urinary profile of <i>de novo</i> purine synthesis intermediates: consequences of the methylfolate trap.","authors":"Jakub Krijt, Václava Škopová, Jitka Sokolová, Marie Zikánová, Petr Chrastina, Samuel Stanovský, Viktor Kožich","doi":"10.1080/15257770.2026.2687453","DOIUrl":"10.1080/15257770.2026.2687453","url":null,"abstract":"<p><p>Vitamin B12 (B12) deficiency may cause severe clinical complications, partly attributable to the \"methylfolate trap\". When B12-dependent methionine synthase activity is impaired, 5-methyltetrahydrofolate (5-MTHF) becomes trapped because it cannot be used in the methionine synthase reaction or reconverted to 5,10-methylenetetrahydrofolate. This reduces the availability of folate cofactors, including tetrahydrofolate (THF), 5,10-methylene-THF, and 10-formyl-THF required for histidine catabolism, pyrimidine metabolism, and <i>de novo</i> purine synthesis (DNPS). We investigated whether this mechanism is reflected in urinary DNPS intermediates. Using LC-MS/MS, we quantified the histidine catabolite formiminoglutamate (FIGLU) and urinary DNPS intermediates in 28 patients with confirmed B12 deficiency and age-stratified controls. Serum methylmalonic acid (MMA) served as a proxy for B12 deficiency severity. Compared with controls, urinary FIGLU and DNPS intermediates-glycinamide ribonucleoside (GAr) and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr)-were significantly increased across all age groups (<i>p</i> < 0.05), while succinyl-5-aminoimidazole-4-carboxamide ribonucleoside (SAICAr) was also increased, except in adults. These changes were more evident in severe B12 deficiency-defined as MMA ≥ 10× the age-specific upper limit (UL): THF depletion was reflected by marked FIGLU elevation (up to several dozen multiples of UL), while reduced folate cofactor availability was demonstrated by increased GAr, SAICAr, and AICAr (up to 3.4-, 2.7-, and 5.0-fold UL, respectively). In linear correlation analyses, urinary FIGLU correlated with serum MMA, and GAr, SAICAr, and AICAr correlated with FIGLU, a marker of THF deficiency (<i>p</i> < 0.05). These findings are consistent with methylfolate trapping, linking B12 deficiency to reduced availability of folate cofactors for histidine catabolism and DNPS.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1164-1175"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318352","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":"Deoxycytidine kinase inhibition: Rewiring tumor nucleotide metabolism for therapeutic gain.","authors":"Peter M Clark, Curtis B Thompson, Kenneth A Schultz","doi":"10.1080/15257770.2026.2647890","DOIUrl":"10.1080/15257770.2026.2647890","url":null,"abstract":"<p><p>Deoxycytidine kinase (dCK) is the rate-limiting enzyme of the deoxyribonucleoside salvage pathway, phosphorylating deoxyadenosine, deoxycytidine, and deoxyguanosine to sustain intracellular deoxyribonucleoside triphosphate (dNTP) pools. Replication stress and DNA damage enhance dCK activity, creating tumor dependence on salvage-mediated dNTP supply for DNA repair and survival. Genetic contexts such as BRCA2 loss and mutant p53 further heighten this vulnerability. This review synthesizes mechanistic evidence linking dCK to stress-adaptive nucleotide metabolism, summarizes progress in small-molecule dCK inhibitor development, and highlights dCK inhibitor TRE-515 as the first clinically tested agent, alongside plasma nucleoside profiling and PET imaging as translational pharmacodynamic biomarkers.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1203-1215"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleoterpenoids on the basis of diterpenoid isosteviol, nucleobases and nucleoside analogues. Synthesis and cytotoxicity of a series of conjugates of isosteviol and uracil. Part 2.","authors":"Olga V Andreeva, Bulat F Garifullin, Alexandra D Voloshina, Anna P Lyubina, Andrey A Parfenov, Irina Yu Strobykina, Mayya G Belenok, Ravil F Aznagulov, Liliya F Saifina, Olga B Babaeva, Vyacheslav E Semenov, Vladimir E Kataev","doi":"10.1080/15257770.2025.2570265","DOIUrl":"10.1080/15257770.2025.2570265","url":null,"abstract":"<p><p>A series of conjugates of diterpenoid isosteviol (16-oxo-<i>ent</i>-beyran-19-oic acid) and uracil (nucleoterpenoids) was synthesized and examined for their <i>in vitro</i> cytotoxicity against 9 human cancer cell lines. Nucleoterpenoids <b>13c</b>,<b>f</b>,<b>15</b> exhibited the best <i>in vitro</i> cytotoxic activity against cancer cell lines M-HeLa, MCF-7, and PC3 (IC₅₀ = 12.7-21.3 µM) among the synthesized compounds. The mechanisms of the <i>in vitro</i> cytotoxic effect of nucleoterpenoids <b>13f</b> and <b>15</b> against M-HeLa cancer cell line (cervical carcinoma) were studied using flow cytofluorometry and enzyme-linked immunosorbent assay (ELISA). The results obtained indicated that <b>13f</b> and <b>15</b> by acting on M-HeLa cancer cells reduced the mitochondrial membrane potential, caused oxidative stress, blocked anti-apoptotic protein Bcl-2, activated apoptosis-initiating caspase-9, thus inducing apoptosis occurring along the mitochondrial pathway. It should be emphasized that although isosteviol and uracil do not have cytotoxicity against human cancer cells, nucleoterpenoids <b>13c</b>,<b>f</b>, and <b>15</b> containing isosteviol and uracil as fragments exhibited good cytotoxicity against M-HeLa, MCF-7, and PC3 cancer cells. Thus, it can be considered that conjugation of diterpenoid isosteviol and nucleic bases is a promising way to search for new cytotoxic agents of unusual structure.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1304-1345"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313323","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":"MiR-922 alleviates LPS-induced HK-2 cell apoptosis and inflammation through TGF-β/Smad.","authors":"Bo Yang, Li Xu, Peng Zhou, Qihao Ma, Yong Li, Danan Sun","doi":"10.1080/15257770.2025.2518554","DOIUrl":"10.1080/15257770.2025.2518554","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs play an extensive role in human chronic kidney diseases (CKD), but the role of miR-922 remains unclear.</p><p><strong>Purpose: </strong>This study was designed to investigate the potential mechanism by which miR-922 acts in CKD.</p><p><strong>Methods: </strong>The human proximal renal tubular cell line (HK-2) was treated by LPS to build a CKD cell model. The expressions of miR-922, TGFβR1, and p-Smad2/3 were detected by RT-qPCR or western blotting. The dual-luciferase reporter assay verified the interaction of miR-922 with TGFβR1. Cell viability and apoptosis were assessed using the CCK-8 assay and Annexin V-FITC/PI method. An ELISA kit was used for the measure of TNF-α/IL-1β levels.</p><p><strong>Results: </strong>MiR-922 was scanty in HK-2 cells with LPS treatment. MiR-922 was an upstream regulator of TGFβR1. The up-regulation of miR-922 restrained TGFβR1 expression, thereby hindering the activation of Smad2/3. Overexpression of miR-922 and inhibition of Smad2/3 alleviated the LPS-induced apoptosis and inflammation, while TGFβR1 played a pro-apoptotic and pro-inflammatory role.</p><p><strong>Conclusion: </strong>MiR-922 rescued HK-2 cell apoptosis and inflammation damage induced by LPS through negative regulation of TGF-β/Smad pathway, which may be a vital molecular mechanism of CKD.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"531-541"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369029","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":"Effect of single strand breaks on the formation of DNA interstrand crosslinks induced by the major oxidative adenine lesion 7,8-dihydro-8-oxoadenine.","authors":"Aaron L Rozelle, Louis B Zhang, Seongmin Lee","doi":"10.1080/15257770.2025.2529353","DOIUrl":"10.1080/15257770.2025.2529353","url":null,"abstract":"<p><p>The major oxidative adenine lesion, 7,8-dihydro-8-oxoadenine (oxoA), can readily undergo further oxidation to generate the highly genotoxic DNA interstrand cross-links (ICLs). Herein we report that the presence of single-strand breaks (SSBs), the major lesion formed at sites of oxidative stress, in the form of a nick or single-nucleotide gap in the phosphodiester backbone of duplex DNA significantly increases the cross-linking yield of oxoA with all canonical nucleotides (up to 67.5%) upon oxidation. The cross-linking reaction occurs between the purine/pyrimidine moiety of a nucleotide on the complementary strand of the duplex and the oxoA modification on the template strand, which was confirmed by the experiment involving the use of 2',3'-dideoxycytosine. Interestingly, the minor cross-linking products in intact DNA saw a more significant increase in reactivity relative to the major oxoA-G ICL. SSBs in the form of a gap or nick between the reacting nucleotide and thymine residue base paired to oxoA produced the most significant increase in yield.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"715-733"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619448","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":"To investigate the molecular mechanism and prognostic value of miR-551a in glioma based on bioinformatics.","authors":"Jiawei Liang, Chaoqiang Zeng, Wendi Li, Peng Zhou","doi":"10.1080/15257770.2025.2551841","DOIUrl":"10.1080/15257770.2025.2551841","url":null,"abstract":"<p><p>Glioma represents the prevalent neoplasm type, distinguished by invasive growth and a significant rate of recurrence. This research investigates the prognostic significance and possible molecular mechanisms of miR-551a in gliomas, thereby offering a novel biomarker for gliomas treatment. This study selected 77 glioma patients and 52 craniocerebral injury patients from 2017 to 2023. The expression of miR-551a was assessed by qPCR. The ROC, Cox regression, and KM curve analyses were conducted to evaluate the diagnostic utility and prognostic value of miR-551a. The effects of inhibiting miR-551a on glioma cell functions were evaluated through CCK-8 and transwell assays. miR-551a target genes was conducted by GO and KEGG enrichment analyses, as well as PPI analysis, to elucidate potential gene regulatory relationship. miR-551a exhibited a significant up-regulation in the cerebrospinal fluid of glioma patients (P < 0.001). miR-551a possessed a robust predictive capacity for gliomas (AUC = 0.792, P < 0.001) and serves as a risk factor for unfavorable prognoses (HR = 3.858, P < 0.01), with patients exhibiting low levels of miR-551a showing favorable prognosis (P = 0.004). The inhibition of miR-551a diminished the proliferative (P < 0.05), migratory (P < 0.01), and invasive (P < 0.001) capabilities of glioma cells. miR-551a functioned as an oncogene, with CALM3 identified as critical regulatory targets (P < 0.001). miR-551a is a biological indicator for glioma prediction. It participates in the disease progression of glioma by regulating the functions of glioma cells via CALM3.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"967-989"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963323","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":"Special issue of the 21^st International Symposium on Purine and Pyrimidine Metabolism in Man.","authors":"","doi":"10.1080/15257770.2026.2732565","DOIUrl":"https://doi.org/10.1080/15257770.2026.2732565","url":null,"abstract":"","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":"45 11","pages":"1107-1108"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063253","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":"Far UV synchrotron radiation circular dichroism of guanine nucleosides.","authors":"Jesse Vanloon, Mariam El-Morched, Jarrett King, Frank Wien, Thad Harroun, Hongbin Yan","doi":"10.1080/15257770.2025.2585120","DOIUrl":"10.1080/15257770.2025.2585120","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1386-1395"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458624","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":"Clinical diagnostic value and potential regulatory mechanisms of lncRNA NOP14-AS1 in chronic kidney disease.","authors":"Hongfang Jiang, Huajuan Shen, Xiujun Xu, Yanna Liu, Yongze Dong, Jiaxiang Jiang","doi":"10.1080/15257770.2025.2456794","DOIUrl":"10.1080/15257770.2025.2456794","url":null,"abstract":"<p><p>In the early stages, chronic kidney disease (CKD) can be asymptomatic, marking diagnosis difficult. This study aimed to investigate the diagnostic role and potential regulatory mechanisms of nucleolar protein 14 (NOP14) -antisense RNA 1 (AS1) in patients with CKD. Herein, 68 patients with CKD, 65 patients with CKD undergoing peridialysis, and 80 healthy adults were included. The real-time reverse transcription-quantitative polymerase chain reaction was performed to assess NOP14-AS1 levels, and its diagnostic value was evaluated using receiver operating characteristic curves. Additionally, cell proliferation and apoptosis were assessed by Cell Counting Kit-8 assay. and flow cytometry, respectively. Oxidative stress levels were determined using superoxide dismutase and malondialdehyde MDA kits, and the dual-luciferase reporter assay was performed to determine the relationship between NOP14-AS1 and microRNA-326 (miR-326) target binding. Lastly, the potential mechanism underlying miR-326 target gene regulation in CKD progression were explored utilizing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Notably, patients with CKD exhibited decreasedNOP14-AS1 levels and upregulated miR-326 levels. NOP14-AS1 and miR-326 exhibited combined effects on cell proliferation, apoptosis, inflammatory factors, and oxidative stress levels. Furthermore, the target genes of miR-326 showed enrichment in CKD-associated rat sarcoma and phosphoinositide 3-kinase protein kinase B pathways. Altogether, the findings of this study show the potential of NOP14-AS1 as a diagnostic marker in CKD. Overall, NOP14-AS1 regulates the miR-326 expression, which, in turn, regulates various miR-326 target gene-associated signaling pathways, thereby affecting the occurrence and development of CKD.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"113-130"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040000","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}