98%
921
2 minutes
20
Coronary artery disease (CAD) is a prevalent cardiovascular condition characterized by the accumulation of plaque within coronary arteries. While distinct features of CAD have been reported, the association between genetic factors and CAD in terms of biomarkers was insufficient. This study aimed to investigate the connection between genetic factors and CAD, focusing on the thymidylate synthase () gene, a gene involved in DNA synthesis and one-carbon metabolism. TS plays a critical role in maintaining the deoxythymidine monophosphate (dTMP) pool, which is essential for DNA replication and repair. Therefore, our research targeted single nucleotide polymorphisms that could potentially impact gene expression and lead to dysfunction. Our findings strongly associate the 1100T>C and 1170A>G genotypes with CAD susceptibility. We observed that 1100T>C polymorphisms increased disease susceptibility in several groups, while the 1170A>G polymorphism displayed a decreasing trend for disease risk when interacting with clinical factors. Furthermore, our results demonstrate the potential contribution of the 1100/1170 haplotypes to disease susceptibility, indicating a synergistic interaction with clinical factors in disease occurrence. Based on these findings, we propose that polymorphisms in the gene had the possibility of clinically useful biomarkers for the prevention, prognosis, and management of CAD in the Korean population.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454159 | PMC |
http://dx.doi.org/10.3390/ijms241612591 | DOI Listing |
Objectives: Vitamin B12 plays a vital role in folate-mediated one-carbon metabolism (FOCM), a series of one-carbon transfer reactions that generate nucleotides (thymidylate (dTMP) and purines) and methionine. Inadequate levels of B12 impair FOCM, depressing de novo thymidylate (dTMP) synthesis, which in turn leads to uracil accumulation in DNA. This phenomenon has been well documented in nuclear DNA.
View Article and Find Full Text PDFChemphyschem
September 2025
Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, The School of Pharmacy, Fujian Medical University, Fuzhou, 350108, P. R. China.
The development of 5-fluorouracil (5-FU) analogs contributes to overcome its side effects and drug resistance. To explore more 5-FU analogs, the substituent effect of BO, NO, and PO on the geometric structure, electronic properties, and reactivity of 5-FU has been systematically studied by density functional theory calculations and molecular docking in this article. It is revealed that the introduced superhalogens can not only form stable covalent bonds with the pyrimidine ring, like the original F atom in 5-FU, but also pose significant effect on the geometric and electronic structures of 5-FU.
View Article and Find Full Text PDFPharmaceutics
August 2025
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 211198, China.
Combining pemetrexed (PEM) with Osimertinib (OSI) improves outcomes in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), but optimal scheduling remains undefined. Sequential PEM → OSI strategies may outperform concurrent administration; however, the critical dosing interval determining synergy has not been explored. : PEM pharmacodynamics were divided into an OSI-antagonized early phase (S-phase arrest and DNA damage accumulation) and OSI-synergized late phase (DNA damage peak, apoptosis initiation, and feedback EGFR activation).
View Article and Find Full Text PDFSci Rep
August 2025
Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Department of Hematology/Oncology and Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
Cancer Drug Resist
July 2025
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Acquired resistance to 5-fluorouracil/leucovorin (5-FU/LV) frequently develops during treatment of metastatic colorectal (mCRC), but the causes are incompletely understood. We aim to: (i) identify the causes of 5-FU/LV resistance under physiological folate; and (ii) determine if a polymeric fluoropyrimidine (FP) CF10 remains potent to CRC cells selected for 5-FU/LV resistance. 5-FU/LV-resistant CRC cells were selected by repeated passaging with increasing 5-FU/LV concentrations, and resistance factors were calculated from dose-response studies.
View Article and Find Full Text PDF