{"title":"In memory of an exquisite medicinal chemist, Prof. Morris Robins.","authors":"Erik De Clercq","doi":"10.1080/15257770.2024.2426160","DOIUrl":"https://doi.org/10.1080/15257770.2024.2426160","url":null,"abstract":"<p><p>Among the most prominent realizations of Morris J. Robins in the antiviral nucleoside chemistry are <i>(i)</i> the synthesis of 8-substituted (methyl-, amino-, bromo-, iodo) derivatives of acyclovir, <i>(ii)</i> xylotubercidin as an inhibitor of herpes simplex virus (HSV) infections, <i>(iii)</i> the anti-HIV activity of the 2',3'-dideoxyriboside of 2,6-diaminopurine (ddDAPR) and the 3'-azido- and 3'-fluoro derivatives thereof (AzddDAPR and FddDAPR, respectively), <i>(iv)</i> the potentiating effect of ribavirin on the anti-HIV activity of 2',3'-dideoxyinosine (ddI) and ddDAPR, <i>(v)</i> S-adenosylhomocysteine hydrolase (SAH) inhibitors principally active against vaccinia virus (VV) and vesicular stomatitis virus (VSV), and <i>(vi)</i> furo[2,3-d]pyrimidinone derivatives active against varicella-zoster virus (VZV).</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591308","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 effect of <i>VEGF</i> and <i>KDR</i> gene variants on Crimean-Congo hemorrhagic fever.","authors":"Laleh Bahrikarehmi, Nilufer Kuruca, Umut Safiye Say Coskun, Ayse Feyda Nursal, Harun Albayrak, Serbulent Yigit","doi":"10.1080/15257770.2024.2423887","DOIUrl":"https://doi.org/10.1080/15257770.2024.2423887","url":null,"abstract":"<p><strong>Background: </strong>Crimean-Congo hemorrhagic fever (CCHF), an acute viral hemorrhagic fever disease, has a high mortality rate among humans. Hemorrhagic propensity is caused by coagulation malfunction and increased capillary permeability brought on by the resultant vascular injury. Vascular endothelial growth factor (VEGF) and VEGF receptor-2, or KDR (kinase insert domain containing receptor), are effective in vasculogenesis and angiogenesis. CCHF was stated to have endothelial dysfunction. This study aimed to evaluate whether the <i>VEGF</i> and <i>KDR</i> gene variants contribute to the development of CCHF in the Turkish population.</p><p><strong>Methods: </strong>A total of 101 subjects, including 51 CCHF patients and 50 healthy controls, were included in the study. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype <i>VEGF</i> 936 C > T (rs3025039) and <i>KDR</i> - 604 T > C (rs2071559) variants. The results were statistically analyzed.</p><p><strong>Results: </strong>The <i>VEGF</i> 936 C > T genotype and allele distributions did differ significantly between the patients and the controls. The subjects carrying the C/C genotype and C allele had a higher risk of developing CCHF than the control group (<i>p˂0.05</i>). There was a statistically significant association between the controls and the patients in terms of <i>VEGF</i> 936 C > T C/C versus C/T + T/T (<i>p˂0.05</i>, OR:3.273, 95%Cl: 1.44-7.63). The <i>KDR</i> - 604 T > C variant's allele and genotype distribution were not significantly different between the patients and controls.</p><p><strong>Conclusion: </strong>This study suggests the <i>VEGF</i> 936 C > T variant is a genetic marker of sensitivity to CCHF among the Turkish population and may help protect against the disease.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576709","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}
Fulya Doğaner, Ahu Soyocak, Didem Turgut Coşan, Merih Özgen, Funda Berkan, Fezan Şahin Mutlu, İrfan Değirmenci, Hasan Veysi Güneş
{"title":"Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in Turkish postmenopausal women with osteoporosis.","authors":"Fulya Doğaner, Ahu Soyocak, Didem Turgut Coşan, Merih Özgen, Funda Berkan, Fezan Şahin Mutlu, İrfan Değirmenci, Hasan Veysi Güneş","doi":"10.1080/15257770.2024.2421302","DOIUrl":"https://doi.org/10.1080/15257770.2024.2421302","url":null,"abstract":"<p><p>Osteoporosis is a common age-related skeletal disease, characterized by changes in the microarchitectural structure of bone tissue and decreased bone mass, especially affecting postmenopausal women. Genetic and environmental factors affecting bone metabolism play a role in the development of osteoporosis. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in the conversion of homocysteine to methionine. Genetic variations in the MTHFR gene lead to impaired function or inactivation of this enzyme. A decrease in MTHFR enzyme activity and an increase in homocysteine levels affect bone metabolism. In this study, we aimed to investigate the relationship between C677T and A1298C polymorphisms and osteoporosis in Turkish postmenopausal women. DNA samples were extracted from 200 volunteers. The PCR-RFLP technique was used to identify the MTHFR gene polymorphisms C677T and A1298C. The statistical significance of the analysis's results was assessed. C677T genotype and allele frequency distributions were not statistically different between postmenopausal osteoporosis and healthy control groups (<i>p</i> = 0.249, <i>p</i> = 0.754), while A1298C genotype and allele frequency distributions were found to be statistically significant (<i>p</i> = 0.002, <i>p</i> = 0.013). The results of our study showed that the A1298C polymorphism may be a genetic factor associated with osteoporosis in this specific population. However, the C677T polymorphism did not show a significant connection. To gain a more comprehensive understanding of the genetic basis of osteoporosis, future research with larger sample sizes and the consideration of additional genetic and environmental factors is essential. Additionally, it is crucial to account for ethnic disparities, gene-gene interactions, and gene-environment interplays. These insights can inform the development of personalized preventive and therapeutic strategies for individuals at risk of osteoporosis in diverse populations.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558377","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":"Association between genetic variants (rs2839698, and rs217727) in <i>lncRNA H19</i> and Acute lymphoblastic leukemia susceptibility: a case-control study in the Iranian population.","authors":"Paria Farhadian, Mohammad Javad Mokhtari","doi":"10.1080/15257770.2024.2422007","DOIUrl":"https://doi.org/10.1080/15257770.2024.2422007","url":null,"abstract":"<p><p>Leukemia is a cancer affecting the hematopoietic system with an unclear pathogenesis. Recent studies suggest a correlation between several long non-coding RNAs (lncRNAs) and leukemia development. This study focuses on the potential link between <i>H19</i> (rs2839698 and rs217727) polymorphisms and Acute Lymphoblastic Leukemia (ALL) susceptibility. The study involved 150 patients with clinically confirmed ALL and 150 controls. This research included 150 Iranian patients, who were confirmed to have clinical ALL, and 150 healthy people as the control group. A kit was utilized to extract the DNA of all the samples. After preparing the samples, DNA genotyping was done by using the tetra-primer ARMS-PCR method. After adjusting for age using multivariate logistic regression analysis, individuals carrying the CT genotype of rs2839698 were found to have a significantly 0.32-fold reduced risk of ALL compared with carriers of the CC genotype. Furthermore, a significant 0.48-fold reduction in ALL risk was observed in patients with CT+TT genotype rs2839698 compared with CC. Moreover, the over-dominant model was applied to compare the CT genotype of rs2839698 with its CC+TT genotype, which showed a significant 0.36-fold reduction of ALL risk. Notably, the cases of ALL and the control group were not significantly different in terms of their genotype and allele frequencies of rs217727 polymorphism. Yet, the TT haplotype was significantly associated with ALL risk (OR: 1.64, <i>p</i> = 0.025). Following the findings of this study, it can be concluded that <i>H19</i> SNP rs2839698, rather than rs217727, might act as an innovative susceptibility marker for ALL leukemia.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522548","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":"Catalytic cleave of an RNA substrate that bypasses the reorganization of its secondary structure during substrate recognition by a <i>trans</i>-acting VS ribozyme.","authors":"Yuki Miyzaki, Ryu Nakane, Shogo Tanishi, Shigeyoshi Matsumura, Yoshiya Ikawa","doi":"10.1080/15257770.2024.2421307","DOIUrl":"https://doi.org/10.1080/15257770.2024.2421307","url":null,"abstract":"<p><p>Varkud satellite ribozyme (VS ribozyme) is a class of catalytic RNA with self-cleavage activity. The wild-type VS ribozyme has structural modularity with a relatively large catalytic module (H2-H6 elements) and a small substrate module (H1 element). The two modules can be dissected physically, and the substrate H1 RNA is recognized and then cleaved by the rest of the parent ribozyme serving as catalytic RNA. We characterized the catalytic properties of a bimolecular VS ribozyme developed and employed for an in-droplet evolution experiment of the VS ribozyme. We examined the effects of polyamines and several divalent metal ions. The results obtained in this study would be useful for the optimization of laboratory evolution of the VS ribozyme.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522549","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}
Shu Wu, Danping Li, Peipei Han, Limei Li, Jun Zhao, Haishan Zhang, Xiaohui Zhou, Ping Li, Yingxi Mo
{"title":"MicroRNA‑374a‑5p/ANLN axis promotes malignant progression of Oral squamous cell carcinoma.","authors":"Shu Wu, Danping Li, Peipei Han, Limei Li, Jun Zhao, Haishan Zhang, Xiaohui Zhou, Ping Li, Yingxi Mo","doi":"10.1080/15257770.2024.2419555","DOIUrl":"https://doi.org/10.1080/15257770.2024.2419555","url":null,"abstract":"<p><strong>Background: </strong>Recent research has revealed a significant association between Anillin (ANLN) and miR-374a‑5p with the progression of tumors. Additionally, bioinformatics analysis indicated an inverse relationship in transcript expression levels between ANLN and miR-374a-5p. However, the specific mechanisms driving the miR-374a-5p/ANLN signaling axis in oral squamous cell carcinoma (OSCC) have not been thoroughly explored.</p><p><strong>Methods: </strong>ANLN and miR-374a‑5p expression were evaluated within OSCC cell lines and tissues by RT-qPCR. Using bioinformatics databases, it has been demonstrated that the ANLN gene could be a target of miR-374a-5p. MiR-374a‑5p and ANLN correlation could be assessed via the dual-luciferase reporter assay and western blotting techniques. Functional studies were employed to investigate the behavioral patterns of miR-374a‑5p within OSCC cells.</p><p><strong>Results: </strong>miR-374a‑5p expression could be remarkably downregulated within both OSCC tissues and cells, coinciding with high ANLN expression. ANLN was a specific target gene for miR-374a‑5p by luciferase function assay. The expression of miR-374a‑5p could serve as a diagnostic biomarker and independently predict a poor prognosis in patients with OSCC, and the counteractive effect of upregulating miR-374a‑5p was observed on the proliferative, migratory, and invasive capabilities of OSCC cells.</p><p><strong>Conclusions: </strong>The findings suggest that the miR-374a‑5p/ANLN signaling axis potentially modulates the advancement of OSCC, and miR-374a‑5p may serve as potential therapeutic targets of oral cancer.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504968","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}
Jainey P James, Mariyam Jouhara B M, Sneh Priya, Divya Jyothi, Rajalakshimi Vasudevan
{"title":"Homology modelling, molecular docking studies and synthesis of aminopyrimidines as inhibitors for deoxynucleoside kinase analogues in cancer chemoprevention.","authors":"Jainey P James, Mariyam Jouhara B M, Sneh Priya, Divya Jyothi, Rajalakshimi Vasudevan","doi":"10.1080/15257770.2024.2417898","DOIUrl":"https://doi.org/10.1080/15257770.2024.2417898","url":null,"abstract":"<p><p>The development of alternative anticancer agents with minimal side effects has become more critical due to the rising recurrence of mammalian malignancies and the severe side effects of chemotherapeutic treatments. Kinases are an essential target for neostatic impact as they play an important role in the modulation of growth factor signalling. Our work aims to screen novel nine-series of thiazole-based aminopyrimidines and sulphaminopyrimidines against the enzymes mitochondrial thymidine kinase 2, deoxyguanosine kinase (2OCP), deoxycytidine kinase (2QRN) and thymidylate kinase (1E2Q) by molecular docking, synthesise and to study their in vitro inhibitory studies. The synthesised compounds were characterised by Infrared, Nuclear magnetic resonance and Mass spectroscopy. In silico studies, compound 4c stands out among the series, with a reported docking score ranging from -6 to -8 Kcal/mol against all the analogue kinases. The in vitro cytotoxicity assay against human small-cell lung carcinoma (A-549) has shown that 5c (IC<sub>50</sub> = 53.9 µM) has an excellent cytotoxic effect over 4c (IC<sub>50</sub>= 68.68 µM). The reason might be the presence of the benzene sulphonamide group, which enhances their anticancer action. To conclude, the compounds 4c and 5c were found to be potent inhibitors of the deoxynucleoside kinases. In vivo studies must further verify these to prove their potent neostatic effect.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504967","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}
Emine Nedime Korucu, Saliha Aydemir, Esma Menevse, Dudu Erkoc Kaya, Ali Ahmed Azzawri
{"title":"Gene expression of MTATP6 and cytochrome P450 in MCF-7 and MDA-MB -231 breast cancer cell lines with juglone and curcumin supplemented.","authors":"Emine Nedime Korucu, Saliha Aydemir, Esma Menevse, Dudu Erkoc Kaya, Ali Ahmed Azzawri","doi":"10.1080/15257770.2024.2418907","DOIUrl":"https://doi.org/10.1080/15257770.2024.2418907","url":null,"abstract":"<p><p>It is aimed to determine the effects of naphthoquinones as juglone and curcumin application on cell viability and expression analyzes of CYP3A4 and MTATP6 genes in MCF-7 and MDA-MB-231 human breast cancer cell lines. MCF-7 and MDA-MB-231 cells were incubated, were replaced with containing various concentrations of 5, 10, 15 μM curcumin and 5, 10, 15 μM juglone for MCF-7 and 1, 5, 10 μM curcumin and 1, 2, 3 μM juglone for MDA-MB-231 for 24 h. CYP3A4 and MTATP6 gene expression levels in both cell lines were determined by quantitative real-time polymerase chain reaction (qPCR) method and western blot method. IC<sub>50</sub> values for 24 h were found as 22.41 μM for curcumin, and 16.27 μM for juglone in MCF-7, and 10.43 μM for curcumin, and 3.42 μM for juglone in MDA-MB-231 cells. Curcumin showed anti-proliferative, and antioxidant effects. CYP3A4 and MTATP6 gene expressions were decreased in MCF-7 breast cancer cell line when the cells treated with juglone or curcumin. CYP3A4 and MTATP6 gene expressions were decreased at all application doses of juglone in MDA-MB-231 cells whereas CYP3A4 and MTATP6 protein levels were only decreased at 10 μM curcumin compared with the control group.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504966","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":"<i>Escherichia coli</i> Orf135 (NudG) mutant protein specific for oxidized dATP.","authors":"Hiroyuki Kamiya","doi":"10.1080/15257770.2024.2413878","DOIUrl":"https://doi.org/10.1080/15257770.2024.2413878","url":null,"abstract":"<p><p>Damaged 2'-deoxyribonucleotides cause mutations, cancer, cell death, and aging. The <i>Escherichia coli</i> Orf135 (NudG) protein catalyzes the hydrolysis of various 2'-deoxyribonucleotides including an oxidized form of dATP, 2-oxo-1,2-dihydro-2'-deoxyadenosine 5'-triphosphate (dA<sup>O</sup>TP, 2-hydroxy-2'-deoxyadenosine 5'-triphosphate). The best substrate is 5-methyl-2'-deoxycytidine 5'-triphosphate (dC<sup>m</sup>TP), and the protein prefers dC<sup>m</sup>TP over dA<sup>O</sup>TP by ∼200-fold in vitro. To make the enzyme specific for the mutagenic nucleotide dA<sup>O</sup>TP, a double mutant protein (E33A plus D118E) was designed and produced in <i>E. coli</i>. The purified mutant protein showed one order of magnitude higher dA<sup>O</sup>TP preference over dC<sup>m</sup>TP. The split protein based on this mutant may potentially be used to detect dA<sup>O</sup>TP in living cells.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406666","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}