Recent results of the authors have demonstrated that the elevation of extracellular adenosine induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), a soluble adenosine prodrug, mediates radioprotective effects in mice. Furthermore, it has been shown that this action is induced by at least two mechanisms: (1) protection by hypoxia as a result of the effects of treatment on the cardiovascular system (bradycardia, vasodilation), and (2) an enhanced regeneration of the radiation-perturbed hematopoiesis. Here, it was ascertained that the joint use of an optimal dose of noradrenaline given with dipyridamole and AMP combination eliminates the hypothermic and hypoxic effects of the treatment, but preserves the radioprotective action of dipyridamole and AMP combination in terms of hematopoietic recovery and partially also survival enhancing effects of the drugs in gamma-irradiated mice. These findings might be of importance for attempts to obtain available and tolerable radioprotective pharmacological prescriptions for clinical use.
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Theranostics
December 2024
Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
: Ferroptosis in lung epithelium and endothelium contributes to the pathogenesis of acute respiratory distress syndrome (ARDS), a critical and often fatal condition marked by acute inflammation and elevated pulmonary vascular permeability. Despite this, there are currently no FDA-approved therapeutics specifically targeting ferroptosis for ARDS management. : A screening of 259 FDA-approved drugs was conducted to identify an effective ferroptosis inhibitor in pulmonary epithelial and endothelial cells.
View Article and Find Full Text PDFMediators Inflamm
May 2024
Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Objective: Microfold cells (M cells) are specific intestinal epithelial cells for monitoring and transcytosis of antigens, microorganisms, and pathogens in the intestine. However, the mechanism for M-cell development remained elusive.
Materials And Methods: Real-time polymerase chain reaction, immunofluorescence, and western blotting were performed to analyze the effect of sorbitol-regulated M-cell differentiation and , and luciferase and chromatin Immunoprecipitation were used to reveal the mechanism through which sorbitol-modulated M-cell differentiation.
Colloids Surf B Biointerfaces
February 2024
Department of Hematology, National Hemophilia Comprehensive Care Center, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China.
The recent "cell-based theory" of coagulation suggests that platelets serve as the site of coagulation factor reactions, making platelets an effective target for inhibiting membrane thrombosis. Unfortunately, there is limited research on how blood purification membranes affect platelet intracellular signaling. In this study, we modified polyethersulfone (PES) membranes with the platelet phosphodiesterase (PDE) inhibitor dipyridamole (DIP) and investigated the effects of the DIP/PES (DP) membranes on platelet adhesion, activation, aggregation, and secretion, as well as the role of the PDE-cyclic adenosine monophosphate (cAMP) intracellular signaling pathway.
View Article and Find Full Text PDFFront Pharmacol
September 2023
Bone and Joint Research Unit, FIIS-Fundación Jiménez Díaz UAM, Madrid, Spain.
: Sarcopenia is defined as a loss of muscle mass and strength. ATP homeostasis is crucial during myogenesis. We determined how the purinergic system modulates myogenesis using dipyridamole (blocks adenosine taken up by the cells) and tenofovir (inhibits ATP release) in a myoblast cell line.
View Article and Find Full Text PDFMediators Inflamm
July 2023
Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
Objective: Vitronectin (VTN) has been reported to trigger cell pyroptosis to aggravate inflammation in our previous study. However, the function of VTN in inflammatory bowel disease (IBD) remains to be addressed.
Methods: Real-time PCR and western blotting were performed to analyze VTN-regulated intestinal epithelial cell (IEC) differentiation through ferroptosis, and immunofluorescence (IF), luciferase, and chromatin immunoprecipitation were used to identify whether VTN-modulated ferroptosis is dependent on phosphodiesterase 4 (PDE4)/protein kinase A (PKA)/cyclic adenosine monophosphate-response element-binding protein (CREB) cascade pathway.
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