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Nature 418:244251 Hebert CG, Valdes JJ, Bentley WE (2008) Beyond silencingengineering applications of RNA interference and antisense technology for altering cellular phenotype

Abbreviations PH: Pulmonary hypertension BMPR2: Bone morphogenetic protein receptor type II E2: Estradiol CYPs: Cytochrome P450s UGTs: UDP-glucuronosyltransferases 2-OHE2: 2-Hydroxyestradiol 4-OHE2: 4-Hydroxyestradiol 2-ME2: 2-Methoxyestradiol HSD17B: 17-Hydroxysteroid dehydrogenase 2-ME1: 2-Methoxyestrone 16-OHE: 16-Hydroxyestrone ER: Estrogen receptor PASMCs: Pulmonary arterial smooth muscle cells PAECs: Pulmonary arterial endothelial cells EndoMT: Endothelial mesenchymal transition ROS: Reactive oxygen species Nrf2: Nuclear factor E2-related factor 2 PPAR: Peroxisome proliferator-activated receptor HIF: Hypoxia-inducible factor SSc: Systemic sclerosis PAH: Pulmonary arterial hypertension ECs: Endothelial cells TGF-: Transforming growth factor- IL: Interleukin TNF: Tumor necrosis factor SMCs: Smooth muscle cells HASMCs: Human aortic smooth muscle cells GPR30: G protein-coupled receptor 30 GSTP: Glutathione S -transferase P COPD: Chronic pulmonary obstruction disease IGF: Insulin-like growth factor References Mocumbi A, Humbert M, Saxena A, Jing ZC, Sliwa K, Thienemann F, Archer SL, Stewart S

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Understanding these sources of oxidative stress is essential for developing targeted therapeutic interventions, including antioxidant supplementation, anti-inflammatory treatments, and lifestyle modifications, to improve sperm function and enhance male fertility (95)

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