A surprisingly low pK(a) (4.3) for a Cu(II) bridging water was found in the presented complex, Cu(2)L, resulting in 3 orders of magnitude higher phosphodiesterase activity on BNPP than Zn(2)L at typical lysosomal pH (~5.0).
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http://dx.doi.org/10.1039/c1cc12466h | DOI Listing |
Life Metab
December 2024
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi 710032, China.
Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most common chronic liver diseases and is mainly caused by metabolic disorders and systemic inflammatory responses. Recent studies have indicated that the activation of the mammalian (or mechanistic) target of rapamycin (mTOR) signaling participates in MASH progression by facilitating lipogenesis and regulating the immune microenvironment. Although several molecular medicines have been demonstrated to inhibit the phosphorylation or activation of mTOR, their poor specificity and side effects limit their clinical application in MASH treatment.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
January 2025
Department of Pharmacology, Federal University of Parana, Curitiba, Parana, Brazil. Electronic address:
Fear generalization, a lack of discrimination between safe and unsafe cues, is a hallmark of posttraumatic stress disorder. The phosphodiesterase 5 (PDE5) regulates the cyclic guanosine monophosphate (cGMP) pathway, which has been proposed to be involved in fear memory generalization. However, whether PDE5 activity underlies fear memory generalization remains unexplored.
View Article and Find Full Text PDFPhosphodiesterase 4B (PDE4B) plays a critical role in cAMP hydrolysis and is highly expressed in brain regions associated with neuroinflammation and central nervous system (CNS) disorders. Selective PDE4B radioligands hold significant potential for elucidating disease mechanisms, such as those in Parkinson's disease and schizophrenia, and enabling target occupancy measurements. In this study, we developed [ F]P4B-2412, a novel PDE4B-selective radioligand, and evaluated its utility for positron emission tomography imaging (PET).
View Article and Find Full Text PDFJ Cereb Blood Flow Metab
January 2025
Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK.
To what extent sildenafil, a selective inhibitor of the type-5 phosphodiesterase modulates systemic redox status and cerebrovascular function during acute exposure to hypoxia remains unknown. To address this, 12 healthy males (aged 24 ± 3 y) participated in a randomized, placebo-controlled crossover study involving exposure to both normoxia and acute (60 min) hypoxia (Fi = 0.14), followed by oral administration of 50 mg sildenafil and placebo (double-blinded).
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
Division of Molecular Psychiatry, Center of Mental Health, University of Hospital Würzburg, 97080 Würzburg, Germany.
Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).
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