Nucleosides, Nucleotides & Nucleic Acids最新文献

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Design, synthesis, and molecular docking evaluation of novel pyrimidine-thiadiazole glycosides as potential anticancer agents. 新型嘧啶-噻二唑糖苷抗癌药物的设计、合成及分子对接评价。
IF 1.3 4区 生物学
Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2026-05-09 DOI: 10.1080/15257770.2026.2664609
Amira A Ghoneim, Abdullah Y Abdullah Alzahrani, Wassila Derafa, Eiman A A Elshaygi, Ahmed Foud El-Farargy
{"title":"Design, synthesis, and molecular docking evaluation of novel pyrimidine-thiadiazole glycosides as potential anticancer agents.","authors":"Amira A Ghoneim, Abdullah Y Abdullah Alzahrani, Wassila Derafa, Eiman A A Elshaygi, Ahmed Foud El-Farargy","doi":"10.1080/15257770.2026.2664609","DOIUrl":"https://doi.org/10.1080/15257770.2026.2664609","url":null,"abstract":"<p><p>A series of novel pyrimidine-thiadiazole conjugates incorporating carbohydrate-based 1,3,4-thiadiazole thioglycosides were synthesized and analyzed using (IR), (<sup>1</sup>H-NMR) and (<sup>13</sup>C-NMR) spectroscopy. The synthesized compounds were evaluated for their cytotoxic activity against human liver <b>(</b>HepG2<b>),</b> breast <b>(</b>MCF-7<b>),</b> and lung <b>(</b>A549<b>)</b> cancer cell lines. Compound <b>10</b> showed the strongest activity with IC<sub>50</sub> values of 10.73 ± 2.04 mM (HepG2), 9.10 ± 1.97 mM (MCF-7), and 9.25 ± 2.94 mM (A549). while <b>6</b> and <b>7</b> demonstrated moderated activity. In contrast, the reference drug doxorubicin exhibited higher potency, with IC<sub>50</sub> values of 3.71 ± 1.12 mM (HepG2), 2.68 ± 0.11 mM (MCF-7), and 3.22 ± 0.22 mM (A549). Molecular docking studies revealed compound <b>10</b> had favorable binding profile with an S-score of -6.33 kcal/mol and RMSD of 3.10 Å, forming key interactions including hydrogen bonding with GLU 142, H-acceptor interaction with GLY 104, and π-H interaction with HIS 141. Compound <b>5</b> also exhibited strong binding interactions (S-score = -5.87 kcal/mol) with multiple metal and ionic interactions, whereas compounds <b>6, 7,</b> and <b>11</b> displayed comparatively weaker binding affinities. These results indicate that compound <b>10</b> is the most promising candidate in this series, with both enhanced cytotoxic activity and favorable docking interactions, suggesting that pyrimidine-thiadiazole hybrids represent a valuable scaffold for further anticancer drug development.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-17"},"PeriodicalIF":1.3,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856798","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}
引用次数: 0
miR-769-5p inhibits cellular behaviors associated with endometriosis progression by directly targeting follistatin in vitro. miR-769-5p通过在体外直接靶向卵泡抑素抑制与子宫内膜异位症进展相关的细胞行为。
IF 1.3 4区 生物学
Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2026-04-30 DOI: 10.1080/15257770.2026.2657461
Yibo Meng, Qinghua Chen, Han Lu
{"title":"miR-769-5p inhibits cellular behaviors associated with endometriosis progression by directly targeting follistatin in vitro.","authors":"Yibo Meng, Qinghua Chen, Han Lu","doi":"10.1080/15257770.2026.2657461","DOIUrl":"https://doi.org/10.1080/15257770.2026.2657461","url":null,"abstract":"<p><p>The pathogenesis of endometriosis (EM) remains intricate and multifactorial. This study aimed to investigate the biological functions of microRNA-769-5p (miR-769-5p) in an <i>in vitro</i> model of EM. Serum was obtained from 120 EM patients and 100 healthy controls. miRNA and mRNA expression were quantified by RT-qPCR. Functional analyses of miR-769-5p were performed in vitrousing cell counting kit-8 (CCK-8) cell proliferation assays, Transwell assays, and dual-luciferase assays in an endometriosis-derived stromal cell line (hEM15A). miR-769-5p was markedly down-regulated in EM sera and correlated inversely with disease severity (<i>p</i> < 0.001). Moreover, miR-769-5p exhibited high diagnostic accuracy for EM (AUC = 0.9166, <i>p</i> < 0.001). In the hEM15A cell model, overexpression of miR-769-5p effectively suppressed the proliferation, migration, and invasion capabilities of EM-derived stromal cells (<i>p</i> < 0.001). miR-769-5p targeted follistatin (FST) and negatively regulated its expression <i>in vitro</i> (<i>p</i> < 0.001). In contrast, FST overexpression could partially reverse the inhibitory effects of miR-769-5p-mimic on these EM-derived cells. Our findings indicate that miR-769-5p is downregulated in EM serum. Furthermore, <i>in vitro</i> experiments suggest that it can target FST to inhibit proliferation, migration, and invasion of ectopic endometrial stromal cells.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-19"},"PeriodicalIF":1.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818452","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}
引用次数: 0
d-Alanyl:d-alanine ligase inhibitors as antibacterial agents against Staphylococcus aureus: a review. d-丙氨酰:d-丙氨酸连接酶抑制剂作为金黄色葡萄球菌抗菌药物的研究进展。
IF 1.3 4区 生物学
Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2026-04-27 DOI: 10.1080/15257770.2026.2661075
Mohammed Afzal Azam, Abisha Thomas, Srikanth Jupudi
{"title":"d-Alanyl:d-alanine ligase inhibitors as antibacterial agents against <i>Staphylococcus aureus</i>: a review.","authors":"Mohammed Afzal Azam, Abisha Thomas, Srikanth Jupudi","doi":"10.1080/15257770.2026.2661075","DOIUrl":"https://doi.org/10.1080/15257770.2026.2661075","url":null,"abstract":"<p><p>Gram-positive pathogen <i>Staphylococcus aureus</i> is associated with human mortality and morbidity worldwide. Mutants of this pathogen is responsible for life threatening community-associated meticillin-resistant infections. Further, the evolution of multidrug-resistant <i>Staphylococcus aureus</i> strains emphasizes the urgent need to develop novel antibacterial agents. ATP-dependent D-alanyl:D-alanine ligase is essential to produce peptidoglycan of bacterial cells, and its inhibition can lead to bacterial cell death, making it a valuable antibacterial target. D-alanyl-D-alanine ligase is recognized as a validated target for the design and development of novel antibacterial agents to overcome resistance problems. In the past several approaches have been used to develop D-alanyl-D-alanine ligase inhibitors with potent antibacterial activity. Some of these inhibitors, including <i>N</i>-acyl-substituted sulfamides, 1-(2-hydroxybenzoyl)-thiosemicarbazide, benzoylthiosemicarbazide, benzoxazoles and diazenedicarboxamides exhibited significant activity against <i>Staphylococcus aureus</i>. The present findings clearly demonstrate that inhibiting D-alanyl:D-alanine ligase is a viable strategy for the discovery of new antibacterial therapies against <i>Staphylococcus aureus</i>.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-21"},"PeriodicalIF":1.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776899","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}
引用次数: 0
Synthesis, structural elucidation, DNA binding, cleavage, cholinesterase inhibitory activity of metal complexes of novel 2,2'-bipyridyl derivative. 新型2,2′-联吡啶衍生物金属配合物的合成、结构解析、DNA结合、裂解及胆碱酯酶抑制活性研究。
IF 1.3 4区 生物学
Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2026-04-27 DOI: 10.1080/15257770.2026.2659226
Ebenezer Bonpandi, Caroline John, Pechiammal Arumugam
{"title":"Synthesis, structural elucidation, DNA binding, cleavage, cholinesterase inhibitory activity of metal complexes of novel 2,2'-bipyridyl derivative.","authors":"Ebenezer Bonpandi, Caroline John, Pechiammal Arumugam","doi":"10.1080/15257770.2026.2659226","DOIUrl":"https://doi.org/10.1080/15257770.2026.2659226","url":null,"abstract":"<p><p>To achieve efficient cholinesterase inhibitory activity of metal(II) complexes of Cu(II), Ni(II), Co(II), and Zn(II) with 2,2'-bipyridyl framework [M-L] (<i>L</i> = 2,2'-bipyridyl derivative containing an aromatic center and an e<sup>-</sup>-withdrawing -NO<sub>2</sub> group) was developed. The structural characteristics were identified through spectroscopic and analytical studies. The antibacterial activity of the produced ligand and metal(II) complexes against bacteria and fungi was evaluated. The synthesized metal(II) complexes ability to fragment DNA has been studied on pUC 18 DNA using agarose gel electrophoresis. The copper(II) complex (K<sub>b</sub>=4.11 × 10<sup>5</sup> M<sup>-1</sup>) is stronger binding affinity for DNA than ethidium bromide (EB) (K<sub>b</sub>=3.3 × 10<sup>5</sup> M<sup>-1</sup>) and metal(II) complexes. The chemically produced 2,2'-bipyridyl derivative had the strongest inhibitory effects against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC<sub>50</sub> values that were less than the standard compounds (0.34 and 3.42 µM, respectively). Our research results could aid in the creation of novel drug molecules, especially for the treatment of neurological conditions like Alzheimer's disease and neurological disorders occurring through diabetes.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-34"},"PeriodicalIF":1.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777166","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}
引用次数: 0
miR-1247-5p is correlated with cervical cancer and regulates cervical cancer cell functions by targeting DVL1. miR-1247-5p与宫颈癌相关,通过靶向DVL1调控宫颈癌细胞功能。
IF 1.3 4区 生物学
Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2026-04-25 DOI: 10.1080/15257770.2026.2655701
Yuhua Yan, Jing Li, Cuiya Zhang, Ruiying Yang, Mengzhen Xie, Jing Zhang
{"title":"miR-1247-5p is correlated with cervical cancer and regulates cervical cancer cell functions by targeting DVL1.","authors":"Yuhua Yan, Jing Li, Cuiya Zhang, Ruiying Yang, Mengzhen Xie, Jing Zhang","doi":"10.1080/15257770.2026.2655701","DOIUrl":"https://doi.org/10.1080/15257770.2026.2655701","url":null,"abstract":"<p><p>The incidence of cervical cancer (CC) is extremely high, yet current diagnostic biomarkers have not achieved satisfactory results. MicroRNAs can regulate vital processes in tumors, including proliferation and apoptosis. The regulatory role of miR-1247-5p in CC remains unknown. This study aims to investigate the diagnostic value of miR-1247-5p in CC. This study included 156 patients with CC and 130 healthy volunteers. Real-time quantitative PCR was used to detect miR-1247-5p and Dishevelled 1 (DVL1) levels. Cell proliferation was assessed using the CCK-8 assay. Levels of Fe2+, lipid reactive oxygen species, malondialdehyde, and glutathione were measured using commercial kits. Diagnostic value of each biomarker was evaluated via receiver operating characteristic curve analysis. miR-1247-5p is significantly downregulated in CC. Low miR-1247-5p constitutes one of the risk factors for CC development. miR-1247-5p mimic inhibits proliferation and promotes ferroptosis. DVL1 is a target of miR-1247-5p. It is upregulated in both serum from CC patients and CC cells. oe-DVL1 partially reverses the suppression of CC malignant behavior by miR-1247-5p mimic. Therefore, we conclude that miR-1247-5p suppresses the malignant behavior of CC by targeting DVL1 and may serve as a potential clinical diagnostic biomarker.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-15"},"PeriodicalIF":1.3,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776897","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}
引用次数: 0
Integrating multi-encoding sequence features via stacking ensemble learning for RNA m5C site prediction. 基于叠加集成学习的多编码序列特征集成RNA m5C位点预测。
IF 1.3 4区 生物学
Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2026-04-20 DOI: 10.1080/15257770.2026.2658190
Ubaid Ur Rahman, Naeem Ul Islam
{"title":"Integrating multi-encoding sequence features via stacking ensemble learning for RNA m5C site prediction.","authors":"Ubaid Ur Rahman, Naeem Ul Islam","doi":"10.1080/15257770.2026.2658190","DOIUrl":"https://doi.org/10.1080/15257770.2026.2658190","url":null,"abstract":"<p><p>RNA 5-methylcytosine (m5C) is an important epitranscriptomic modification involved in RNA stability, translation, and post-transcriptional regulation. Accurate identification of m5C sites remains challenging due to limited sequence representation and insufficient feature integration in existing computational methods. In this study, we propose a comprehensive machine learning framework that integrates six complementary sequence encoding schemes, including enhanced nucleic acid composition (ENAC), tri-nucleotide composition (TNC), composition of K-spaced nucleic acid pairs (CKSNAP), pseudo-electron-ion interaction potential (PseEIIP), one-hot encoding, and nucleotide chemical properties (NCP). Each encoding is paired with an optimal classifier, and a stacking ensemble strategy is employed to fuze the outputs of base classifiers. The model is trained using 5-fold cross-validation for base learners and 3-fold cross-validation for the meta-learner. Performance evaluation using multiple metrics demonstrates that the proposed approach achieves improved robustness and cross-dataset generalization, with an accuracy of 75.5%, MCC of 0.51, and PR-AUC of 0.82. These results indicate that the proposed fusion-based ensemble framework provides an effective and reliable solution for RNA m5C site prediction.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-29"},"PeriodicalIF":1.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729160","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}
引用次数: 0
CRISPR Cas9 mediated genome editing to induce apoptosis a new strategy to tackle cancer. CRISPR Cas9介导的基因组编辑诱导细胞凋亡——治疗癌症的新策略
IF 1.3 4区 生物学
Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2026-04-17 DOI: 10.1080/15257770.2026.2656460
Saqib Hussain Hadri, Faizan Ahmad, Ayesha Malik, Saleha Afzal, Numan Ijaz, Maryam Farhat, Areej Fatima
{"title":"CRISPR Cas9 mediated genome editing to induce apoptosis a new strategy to tackle cancer.","authors":"Saqib Hussain Hadri, Faizan Ahmad, Ayesha Malik, Saleha Afzal, Numan Ijaz, Maryam Farhat, Areej Fatima","doi":"10.1080/15257770.2026.2656460","DOIUrl":"https://doi.org/10.1080/15257770.2026.2656460","url":null,"abstract":"<p><p>CRISPR-Cas9 is a strong gene editing tool having two components, Cas9 protein and guide RNA. It involves a protospacer adjacent motif (PAM) which is identified by Cas9 endonucleases to initiate double stranded break in DNA, which is repaired by either of two pathways; non-homologous end joining pathway (NHEJ) or homology-directed repair (HDR) pathway .CRISPR/Cas9 can be used to edit the genes involved in apoptosis regulation, to target oncogenes, anti-apoptotic proteins, immune checkpoints, to selectively induce cancer cell death. This review identifies CRISPR-mediated apoptotic approaches, its mechanism, preclinical trials, and issues and points to its possible application in cancer.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-22"},"PeriodicalIF":1.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699351","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}
引用次数: 0
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. covid后n -甲基-2-吡酮-5-羧酰胺(Met2PY)和n -甲基-4-吡酮-3-羧酰胺(Met4PY)增加与炎症和内皮活化标志物相关。
IF 1.3 4区 生物学
Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2026-04-07 DOI: 10.1080/15257770.2026.2650677
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
{"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":"https://doi.org/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<sup>+</sup> homeostasis becomes dys-regulated, with excessive NAD<sup>+</sup> consumption and enhanced catabolic flux through nicotinamide methylation pathways. This imbalance leads to NAD<sup>+</sup> 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<sup>+</sup> 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":"1-14"},"PeriodicalIF":1.3,"publicationDate":"2026-04-07","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}
引用次数: 0
Suppression of PANC-1 pancreatic cancer cell proliferation by gemcitabine and ultrasound-mediated microbubble therapy. 吉西他滨和超声介导的微泡治疗抑制胰腺癌PANC-1细胞增殖。
IF 1.3 4区 生物学
Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2026-04-01 DOI: 10.1080/15257770.2026.2649863
Sila Appak-Baskoy, Zlatina Naydenova, Mathew Rajic, Raffi Karshafian, Michael C Kolios, Imogen R Coe
{"title":"Suppression of PANC-1 pancreatic cancer cell proliferation by gemcitabine and ultrasound-mediated microbubble therapy.","authors":"Sila Appak-Baskoy, Zlatina Naydenova, Mathew Rajic, Raffi Karshafian, Michael C Kolios, Imogen R Coe","doi":"10.1080/15257770.2026.2649863","DOIUrl":"https://doi.org/10.1080/15257770.2026.2649863","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is among the most treatment-resistant malignancies, characterized by aggressive progression and limited drug penetration reducing chemotherapeutic efficacy. Gemcitabine, a pyrimidine nucleoside analog and standard-of-care therapy for PDAC, remains clinically important but is limited by the emergence of resistant tumor cell populations that underscore the need for strategies that enhance cytotoxic efficacy and overcome adaptive resistance mechanisms. Ultrasound-stimulated microbubble (USMB) therapy has emerged as a noninvasive, mechanically driven approach capable of transiently perturbing cellular membranes and enhancing therapeutic responses. We hypothesized that gemcitabine-induced metabolic and structural alterations may sensitize PDAC cells to subsequent disruption by USMB, resulting in enhanced cell death. To test this hypothesis, we assessed changes in proliferation, morphology, and cell death following gemcitabine and USMB treatments administered individually and in sequence to PANC-1 cells. Gemcitabine treatment alone (2 µM for 48h) significantly reduced cell proliferation by approximately 22% and induced pronounced morphological remodeling, including statistically increased average cell diameter from ∼19 µm to ∼22 µm, consistent with cytoplasmic expansion and structural reorganization. Notably, when gemcitabine-treated cells were subsequently exposed to USMB (1 MHz, 770 kPa negative pressure for 1 min), cell death increased dramatically to >80%, significantly exceeding the effects observed with either gemcitabine or USMB monotherapy indicating that gemcitabine pretreatment induces a mechanically vulnerable cellular state that can be exploited by USMB to achieve synergistic cytotoxicity. Therefore, the proposed combined biochemical-biophysical strategy offers a promising approach to suppress the rapid compensatory growth and therapeutic resistance commonly associated with monotherapy failure in PDAC cells.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"1-13"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593185","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}
引用次数: 0
Deoxycytidine kinase inhibition: Rewiring tumor nucleotide metabolism for therapeutic gain. 脱氧胞苷激酶抑制:重新布线肿瘤核苷酸代谢治疗增益。
IF 1.3 4区 生物学
Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2026-03-26 DOI: 10.1080/15257770.2026.2647890
Peter M Clark, Curtis B Thompson, Kenneth A Schultz
{"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":"1-13"},"PeriodicalIF":1.3,"publicationDate":"2026-03-26","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}
引用次数: 0
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