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Pharmacological ascorbate combined with rucosopasem selectively radio-chemo-sensitizes NSCLC via generation of HO.

Redox Biol

January 2025

Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa College of Medicine, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, 52242, USA.

Differences in cancer and normal cell oxidative metabolism provide a unique therapeutic opportunity for developing combined modality approaches with redox-active small molecules as radio-chemosensitizers that are well-tolerated by normal tissues. Pentaazamacrocyclic Mn (II)-containing (MnPAM) superoxide dismutase (SOD) mimetics and pharmacological ascorbate given IV to achieve [mM] plasma levels (pharmacological ascorbate: P-AscH‾) have been shown to act individually as cancer cell radio- and chemosensitizers via the generation of HOin vivo. The current study shows that the combination of newly developed MnPAM dismutase mimetic, rucosopasem manganese (RUC) with P-AscH‾ radio-sensitizes non-small cell lung cancer cells (NSCLC) and increases steady state levels of intracellular HO with no additional toxicity to normal human bronchial epithelial cells (HBECs).

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Lipid Levels and Lung Cancer Risk: Findings from the Taiwan National Data Systems from 2012 to 2018.

J Epidemiol Glob Health

January 2025

Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, No.7, Chung Shan S. Rd., Zhongzheng District, Taipei City, 100225, Taiwan.

Background: Lipids are known to be involved in carcinogenesis, but the associations between lipid profiles and different lung cancer histological classifications remain unknown.

Methods: Individuals who participated in national adult health surveillance from 2012 to 2018 were included. For patients who developed lung cancer during follow-up, a 1:2 control group of nonlung cancer participants was selected after matching.

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Glycolysis is a conserved metabolic pathway that converts glucose into pyruvate in the cytosol, producing ATP and NADH. In and several other apicomplexan parasites, some glycolytic enzymes have isoforms located in their plastid (called the apicoplast). In this organelle, glycolytic intermediates like glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) are imported from the cytosol and further metabolized, providing ATP, reducing power, and precursors for anabolic pathways such as isoprenoid synthesis.

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Skeletal muscle regeneration in adults is predominantly driven by satellite cells. Loss of satellite cell pool and function leads to skeletal muscle wasting in many conditions and disease states. Here, we demonstrate that the levels of fibroblast growth factor-inducible 14 (Fn14) were increased in satellite cells after muscle injury.

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Dental manifestations of hypophosphatasia: translational and clinical advances.

JBMR Plus

February 2025

Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, 43210, United States.

Hypophosphatasia (HPP) is an inherited error in metabolism resulting from loss-of-function variants in the gene, which encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP plays a crucial role in biomineralization of bones and teeth, in part by reducing levels of inorganic pyrophosphate (PP), an inhibitor of biomineralization. HPP onset in childhood contributes to rickets, including growth plate defects and impaired growth.

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