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A high percentage of cells in S-phase is associated with a better clinical response to MTX ( TYMS , CPTS , and an MTX target enzyme, DHFR ( via AMPK activation ( In parallel with MTXs most well-known targets, several NAD+-dependent enzymes were inhibited by the antifolate in vitro : 2-oxoglutarate, isocitrate, malate, pyruvate, succinate, 6-phosphogluconate and glucose-6-phosphate dehydrogenases, glutamate-cysteine ligase, glutathione reductase, and glutathione peroxidase ( in vitro and in vivo , resulting in decreased levels of S-adenosylmethionine (SAM) ( Despite the number and importance of such enzymes to cellular metabolism, few studies have been conducted to better understand the effects of MTX on cellular metabolic homeostasis or find metabolic fragilities that could be exploited clinically

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Back to Journals International Journal of General Medicine Volume 18 Unravelling the Silence: Exploring Tinnitus Pathophysiology and the Promise of Traditional Chinese Medicine Authors Xing Q, Jiang Y, Xu D, Hou Z, Xu J Received 19 June 2025 Accepted for publication 28 August 2025 Published 16 December 2025 Volume 2025:18 Pages 75597577 DOI Checked for plagiarism Yes Review by Single anonymous peer review Peer reviewer comments 2 Editor who approved publication: Dr Woon-Man Kung Qingchang Xing, Yueying Jiang, Dongye Xu, Zhiming Hou, Jichao Xu Department of Traditional Chinese Medicine, The Eighth Medical Center of PLA General Hospital, Beijing, Peoples Republic of China Correspondence: Jichao Xu, Department of Traditional Chinese Medicine, The Eighth Medical Center of PLA General Hospital, 17 Heishan Hujia, Haidian District, Beijing, Peoples Republic of China, Email [email protected] Abstract: Tinnitus is a prevalent condition often associated with hearing loss