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Chronotropic effects of milrinone in a guinea pig ex vivo model: a pilot study to screen for new mechanisms of action.
J Cardiovasc Pharmacol
January 2025
Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Positive inotropic responses upon administration of milrinone, an inhibitor of the phosphodiesterase enzyme (PDE), involve a well-pronounced positive chronotropic effect. Here we tested whether milrinone evokes this chronotropic response solely by PDE inhibition or by a concerted action that involve additional pharmacological targets. Milrinone stimulated increases in heart rate were studied in right atrial preparations of guinea pig in the presence or absence of inhibitors of putative ancillary molecular pathways or ion channels: i.
View Article and Find Full Text PDFBone Marrow Mononuclear Cell Transplantation Promotes Bone Healing via Gap Junction-Mediated Cell-Cell Interaction.
Stem Cells
January 2025
Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe city, Hyogo 650-0017, Japan.
Aims: Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells that have been widely used in experimental therapies for patients with various diseases, including fractures.Activation of angiogenesis is believed to be one of the major modes of action of BM-MNCs; however, the essential mechanism by which BM-MNCs activate angiogenesis remains elusive. This study aimed to demonstrate that BM-MNCs promote bone healing by enhancing angiogenesis through direct cell-to-cell interactions via gap junctions, in addition to a previously reported method.
View Article and Find Full Text PDFAntibacterials with Novel Chemical Scaffolds in Clinical Development.
Drugs
January 2025
Department of Chemical Biology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124, Braunschweig, Germany.
The rise of antimicrobial resistance represents a significant global health threat, driven by the diminishing efficacy of existing antibiotics, a lack of novel antibacterials entering the market, and an over- or misuse of existing antibiotics, which accelerates the evolution of resistant bacterial strains. This review focuses on innovative therapies by highlighting 19 novel antibacterials in clinical development as of June 2024. These selected compounds are characterized by new chemical scaffolds, novel molecular targets, and/or unique mechanisms of action, which render their potential to break antimicrobial resistance particularly high.
View Article and Find Full Text PDFStudy of the Pharmacological Activity Spectrum of the New Original NT-3 Mimetic Dipeptide GTS-302.
Dokl Biochem Biophys
January 2025
Center for Strategic Planning and Management of Biomedical Health Risks, Federal Medical and Biological Agency, Moscow, Russia.
Unlabelled: The association of the pathogenesis of neurodegenerative diseases, depression, anxiety, and cognitive disorders with neurotrophin-3 deficiency determines the prospect of creating drugs with a similar mechanism of action. Since the use of full-length NT-3 is limited by unsatisfactory pharmacokinetic properties, the creation of low-molecular mimetics of neurotrophin-3 that are active when administered systemically is relevant. The Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies has created a dimeric dipeptide mimetic of the 4th loop of NT-3, hexamethylenediamide bis-(N-γ-oxybutyryl-L-glutamyl-L-asparagine) with the laboratory code GTS-302, which activates TrkC and TrkB receptors.
View Article and Find Full Text PDFOmega-3 Docosahexaenoic Acid as a Promising Inducer of Ferroptosis: Dynamics of Action in Prostate and Colorectal Cancer Models.
Dokl Biochem Biophys
January 2025
National Research University Higher School of Economics, Moscow, Russia.
Ferroptosis is an iron-dependent form of programmed cell death (PCD) associated with lipid membrane peroxidation. It has gained attention in cancer research because some tumor cells that are resistant to other forms of PCD are sensitive to ferroptosis. Despite the significant amount of research on ferroptosis, the list of known inducers remains limited, creating opportunities to discover new compounds with clinical potential.
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