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Phosphodiesterase Type 5 Inhibitors in Male Reproduction: Molecular Mechanisms and Clinical Implications for Fertility Management.
Cells
January 2025
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Phosphodiesterases, particularly the type 5 isoform (PDE5), have gained recognition as pivotal regulators of male reproductive physiology, exerting significant influence on testicular function, sperm maturation, and overall fertility potential. Over the past several decades, investigations have expanded beyond the original therapeutic intent of PDE5 inhibitors for erectile dysfunction, exploring their broader reproductive implications. This narrative review integrates current evidence from in vitro studies, animal models, and clinical research to clarify the roles of PDEs in effecting the male reproductive tract, with an emphasis on the mechanistic pathways underlying cyclic nucleotide signaling, the cellular specificity of PDE isoform expression, and the effects of PDE5 inhibitors on Leydig and Sertoli cell functions.
View Article and Find Full Text PDFModulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders.
Cells
January 2025
Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling, respectively, which are vital for learning, memory, and neuroprotection. This review synthesizes current evidence on the roles of PDE4 and PDE5 in neurological health and disease, focusing on their regulation of second messenger pathways and their implications for brain function.
View Article and Find Full Text PDFRepurposing of phosphodiesterase-5 inhibitor sildenafil as a therapeutic agent to prevent gastric cancer growth through suppressing c-MYC stability for IL-6 transcription.
Commun Biol
January 2025
Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Phosphodiesterase-5 (PDE5) inhibitors have shown promise as anti-cancer agents in malignancies. However, their specific effects on gastric cancer (GC) and the underlying mechanisms remain elusive. Our aim was to investigate this by combining evidence from population-based studies with data obtained from in vivo and in vitro experiments.
View Article and Find Full Text PDFA New and Safe Delivery of Sildenafil Citrate Co-Evaporate Loaded Emulgels for the Cure of Certain Male Sexual Dysfunctions.
AAPS PharmSciTech
January 2025
Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Assiut University, Assiut, Egypt.
The present work focuses on the production of sildenafil co-evaporates loaded emulgels as topical dosage forms for the treatment of premature ejaculation and erectile dysfunction. Topical administration of sildenafil citrate (SILD) co-evaporates is expected to improve the bioavailability profile of the drug and to avoid the severe side effects accompanying the traditional SILD dosage forms, especially for prohibited cardiovascular cases. Firstly, the solubility of SILD was improved via solid dispersion via co-evaporation technique using PEG-5KDa and PVP-K90 as hydrophilic carriers.
View Article and Find Full Text PDFDefining proteoform-specific interactions for drug targeting in a native cell signalling environment.
Nat Chem
January 2025
Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford, UK.
Understanding the dynamics of membrane protein-ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer.
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