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Cordia oncocalyx and oncocalyxones: From the phytochemistry to the anticancer action and therapeutic benefits against chronic diseases.
Fitoterapia
September 2023
Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
Cordia oncocalyx Allemão is an endemic economically underexploited plant from Brazilian semi-arid region. Herein, we carried out a well-defined bibliographic review about the pharmacological activities of oncocalyxones from C. oncocalyx and mechanisms responsible for the biomedical properties.
View Article and Find Full Text PDFFifty years with aspirin and platelets.
Br J Pharmacol
January 2023
Department of Pharmacology, Catholic University School of Medicine, Rome, Italy.
In 2021, we reached the 50th anniversary of the publication of Sir John Vane's seminal paper in Nature New Biology describing the experiments supporting his mechanistic hypothesis that inhibition of prostaglandin synthesis might explain the main pharmacological effects of aspirin and aspirin-like drugs, that is, reduction in pain, fever and inflammation. Bengt Samuelsson's subsequent discoveries elucidating the cyclooxygenase pathway of platelet arachidonic acid metabolism motivated my research interest towards measuring platelet thromboxane A biosynthesis as a tool to investigate the clinical pharmacology of cyclooxygenase inhibition by aspirin in health and disease. What followed was a long, winding road of clinical research leading to the characterization of low-dose aspirin as a life-saving antiplatelet drug that still represents the cornerstone of antithrombotic therapy.
View Article and Find Full Text PDFProstaglandin E-EP4 Axis Promotes Lipolysis and Fibrosis in Adipose Tissue Leading to Ectopic Fat Deposition and Insulin Resistance.
Cell Rep
October 2020
Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan; FORCE, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan. Electronic address:
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- * The study identifies the role of the adipocyte prostaglandin E-EP4 receptor signaling in regulating basal lipolysis and fat distribution, especially during periods of feeding and fasting.
- * The PGE-EP4 pathway interacts with insulin to maintain balanced lipolysis, and disturbances in this signaling may contribute to a condition known as "metabolically healthy obesity."
Diflunisal targets the HMGB1/CXCL12 heterocomplex and blocks immune cell recruitment.
EMBO Rep
October 2019
Biomolecular NMR Laboratory, Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milan, Italy.
Extracellular HMGB1 triggers inflammation following infection or injury and supports tumorigenesis in inflammation-related malignancies. HMGB1 has several redox states: reduced HMGB1 recruits inflammatory cells to injured tissues forming a heterocomplex with CXCL12 and signaling via its receptor CXCR4; disulfide-containing HMGB1 binds to TLR4 and promotes inflammatory responses. Here we show that diflunisal, an aspirin-like nonsteroidal anti-inflammatory drug (NSAID) that has been in clinical use for decades, specifically inhibits in vitro and in vivo the chemotactic activity of HMGB1 at nanomolar concentrations, at least in part by binding directly to both HMGB1 and CXCL12 and disrupting their heterocomplex.
View Article and Find Full Text PDFA novel mechanism for the anticancer activity of aspirin and salicylates.
Int J Oncol
April 2019
Department of Biomedical Science and Physiology, School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.
Epidemiological studies indicate that long‑term aspirin usage reduces the incidence of colorectal cancer (CRC) and may protect against other non‑CRC associated adenocarcinomas, including oesophageal cancer. A number of hypotheses have been proposed with respect to the molecular action of aspirin and other non‑steroidal anti‑inflammatory drugs in cancer development. The mechanism by which aspirin exhibits toxicity to CRC has been previously investigated by synthesising novel analogues and derivatives of aspirin in an effort to identify functionally significant moieties.
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