A study of pH dependence for ppp5'A2'p5'A2'p5'A hydrolysis in interferon treated and untreated mouse L-cells extracts led to the detection of two types of the 2'-phosphodiesterase activities: interferon dependent and interferon resistant. Several pH-optima were observed for hydrolysis of ppp5'A2'p5'A2'p5'A in cell extracts after their treatment with non-ionic detergent NP-40 or their differential centrifugation. The 2'-phosphodiesterase activity was found in the membrane fraction as well as in the cytoplasmic one. The presence of several pH-optima for 2'-phosphodiesterase activity in L-cells and changes of the level of this activity depending on the growth stage of cells and time of their interferon treatment indicate the complicated character of the regulation of 2'-5'-oligoadenylate's concentration and localization. The results obtained suggest that in mouse L-cells several 2'-phosphodiesterases or one enzyme in different forms may be present.
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Eur J Med Chem
January 2025
School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China. Electronic address:
Based on the molecular hybridization strategy, novel thienopyridine indole derivatives were designed and synthesized as tubulin polymerization inhibitors, and the in vitro antiproliferative potency on MGC-803, KYSE450 and HCT-116 cells was evaluated. Among them, compound 20b showed a broad-spectrum antiproliferative activity against 11 cancer cell lines, with IC values below 4 nmol/L. Notably, it demonstrated exceptional efficacy against MGC-803 (IC = 1.
View Article and Find Full Text PDFSci Adv
December 2024
Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université catholique de Louvain, 1200 Brussels, Belgium.
Modulating the endogenous stores of gastrointestinal hormones is considered a promising strategy to mimic gut endocrine function, improving metabolic dysfunction. Here, we exploit mouse and human knock-in and knockout intestinal organoids and show that agents used as commercial lipid excipients can activate nutrient-sensitive receptors on enteroendocrine cells (EECs) and, when formulated as lipid nanocarriers, can bestow biological effects through the release of GLP-1, GIP, and PYY from K and L cells. Studies in wild-type, dysglycemic, and gut knockout mice demonstrated that the effect exerted by lipid nanocarriers could be modulated by varying the excipients (e.
View Article and Find Full Text PDFMol Metab
January 2025
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan. Electronic address:
Objectives: Arginine vasopressin (AVP), known as an antidiuretic hormone, is also crucial in metabolic homeostasis. Although AVP receptor-deficient mice exhibit various abnormalities in glucose and lipid metabolism, the mechanism underlying these symptoms remains unclear. This study aimed to explore the involvement of the gut hormones including glucagon-like peptide-1 (GLP-1) and microbiota as essential mediators.
View Article and Find Full Text PDFJ Physiol
December 2024
Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China.
J Exp Clin Cancer Res
November 2024
The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, 84105, Beer-Sheva, Israel.
Background: Basket clinical trials targeting the KRAS-mutation in solid tumors have shown initial promise, including in orphan KRAS head and neck cancer (HNC). However, development of resistance to KRAS-mutant-specific inhibitors (KRASi) remains a major obstacle. Here, we investigated the intrinsic (tumor-cell autonomus) and tumor-microenvironment (TME) mechanisms of resistance to the KRASi-MRTX849 and AMG510 in a unique syngenic murine KRAS-mutated HNC cell line.
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