The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-O-methyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD.
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http://dx.doi.org/10.1186/1477-7827-7-4 | DOI Listing |
Drug Des Devel Ther
December 2024
Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.
Purpose: Ciprofol is a novel intravenous anesthetic that has been increasingly used in clinical anesthesia and sedation. Studies suggested that ciprofol reduced oxidative stress and inflammatory responses to alleviate cerebral ischemia/reperfusion (I/R) injury, but whether ciprofol protects the heart against I/R injury and the mechanisms are unknown. Herein, we assessed the effects of ciprofol on ferroptosis during myocardial I/R injury.
View Article and Find Full Text PDFFEBS J
December 2024
Department of Colorectal Surgery, New Taipei Municipal Tucheng Hospital, Taiwan.
Hypoxia is a critical microenvironmental factor that induces tumorigenesis and cancer progression, including metastasis. The highly dynamic nature of the extracellular matrix (ECM) plays a crucial role in metastasis. Collagens are the predominant component of structural proteins embedded within the ECM.
View Article and Find Full Text PDFRadiother Oncol
December 2024
Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University,Guangzhou,510000,China. Electronic address:
Purpose: Radiotherapy presents a curative approach for nasopharyngeal carcinoma (NPC); however, the cellular radiosensitivity heterogeneity limits its efficacy. Thus, investigating the specific mechanisms of radioresistance in NPC is crucial for identifying and employing effective radiosensitizing agents to enhance treatment success.
Methods And Materials: Radioresistant NPC cell lines HONE1-RR and SUNE1-RR were established.
Cell Mol Biol (Noisy-le-grand)
November 2024
Eskişehir Osmangazi University, Medical Faculty, Department of Biostatistics, Eskişehir, Türkiye.
Neuroblastoma shows the highest lethality in childhood and has poor prognosis at high grade. Our objectives included determining how retinoic acid affected the growth of neuroblastoma cells and the relationship between chemicals unique to neurons and cell death processes like apoptosis and mitophagy. The 50% inhibitory concentration of retinoic acid on SH-SY5Y neuroblastoma cells was determined at the 24th, 48th and 72nd hours.
View Article and Find Full Text PDFExp Eye Res
December 2024
Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:
We investigated the mechanism of action of atropine in myopia control by examining its effect on choroidal hemodynamics. Blood flow was evaluated using indocyanine green (ICG) fluorescence and molecular variation during the development of form-deprivation myopia (FDM) and atropine treatment in guinea pigs. Guinea pigs were divided randomly into the normal control (NC), FDM, and FDM + 1% atropine (ATR) groups, and evaluated by spherical equivalent refractive error (SE) and axial length (AL).
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