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Prognostic significance and therapeutic potential of guanosine triphosphate cyclohydrolase 1 in esophageal squamous cell carcinoma: clinical implications of ferroptosis and lipid peroxidation regulation.
Front Oncol
December 2024
Department of Human Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Background: Esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC), is a leading cause of cancer-related death and has a poor prognosis. Despite the advancements in multidisciplinary therapies, resistance to conventional treatments warrants the development of novel therapeutic strategies. Ferroptosis, a form of cell death dependent on intracellular iron, has emerged as a potential mechanism for targeting cancer cells resistant to apoptosis.
View Article and Find Full Text PDFGenetic Diversity and Expanded Phenotypes in Dystonia: Insights from Large-Scale Exome Sequencing.
medRxiv
December 2024
Institute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.
Article Synopsis
- Dystonia is a common movement disorder with a complex genetic background, showing significant variability in its clinical presentation and genetics.
- The study involved exome sequencing of nearly 1,924 patients, mainly from two major registries, focusing on those with genetic prescreening negative results and early age at onset.
- Researchers discovered 137 likely pathogenic variants in 51 genes among the patients, with many being novel, highlighting the challenges in diagnosing and understanding the disorder's genetic links.
Cross-species RNAi therapy via AAV delivery alleviates neuropathic pain by targeting GCH1.
Neurotherapeutics
December 2024
Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Neurosurgery, Brain Research institute, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:
Tetrahydrobiopterin (BH4) expression is normally strictly controlled; however, its intracellular levels increase considerably following nerve damage. GTP cyclohydrolase I (GCH1) plays a crucial role in regulating BH4 concentration, with an upregulation observed in the dorsal root ganglion in cases of neuropathic pain. In this study, we aimed to develop and evaluate the clinical potential of an RNA interference-based adeno-associated virus (AAV) targeting GCH1 across various species to decrease BH4 levels and, consequently, alleviate neuropathic pain symptoms.
View Article and Find Full Text PDFBroadening horizons: the multifaceted role of ferroptosis in breast cancer.
Front Immunol
December 2024
Department of Rheumatology, The First People's Hospital Changde City, Changde, Hunan, China.
Article Synopsis
- - Breast cancer is a major global health issue for women, often complicated by current treatments like chemotherapy and radiotherapy that can lead to drug resistance and poor outcomes due to mechanisms like anti-apoptosis.
- - Ferroptosis is a new form of cell death linked to factors such as iron overload and oxidative stress, which has been shown to hinder cancer cell growth and increase sensitivity to standard treatments.
- - The paper reviews the mechanisms and signaling pathways involved in ferroptosis related to breast cancer, highlighting the need for more research to better understand its regulatory factors and improve treatment strategies.
Novel Role of 5-Methyl-(6S)-Tetrahydrofolate in Mediating Endothelial Cell Tetrahydrobiopterin in Pregnancy and Implications for Gestational Hypertension.
Hypertension
September 2024
Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, Radcliffe Department of Medicine (Y.D., G.D., K.M.C., S.C.).
Background: Folate intake during pregnancy is essential for fetal development and maternal health. However, the specific effects of folic acid (FA) and 5-methyl-(6S)-tetrahydrofolate (5-MTHF) on the prevention and treatment of hypertensive disorders of pregnancy remain unclear. We investigated whether FA and 5-MTHF have different effects on endothelial cell tetrahydrobiopterin (BH4) metabolism in pregnancy and the possible consequences for endothelial NO generation, maternal blood pressure, and fetal growth.
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