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Synthesis and biological evaluation of new dual APN/NEP inhibitors as potent analgesics.
Bioorg Chem
January 2025
School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address:
An alternative approach for the management of acute and chronic pains involves prolonging the half-life of endogenous opiates, such as enkephalins that are released in response to nociceptive stimuli. This can be achieved through the inhibition of enzymatic pathways responsible for the hydrolysis of these peptides, particularly targeting Aminopeptidase N (APN) and Neutral Endopeptidase (NEP). In this study, we designed and synthesized a series of dual enkephalinase inhibitors (DENKIs) targeting both APN and NEP as novel analgesic treatments.
View Article and Find Full Text PDFDestined for destruction: The role of methionine aminopeptidases and plant cysteine oxidases in N-degron formation.
Plant Physiol
December 2024
Department of Biology, University of Oxford, South Parks Road, Oxford OX1 3RB, UK.
The cysteine/arginine (Cys/Arg) branch of the N-degron pathway controls the stability of certain proteins with methionine (Met)-Cys N-termini, initiated by Met cleavage and Cys oxidation. In seeding plants, target proteins include the Group VII Ethylene Response Factors, which initiate adaptive responses to low oxygen (hypoxic) stress, as well as Vernalization 2 (VRN2) and Little Zipper 2 (ZPR2), which are involved in responses to endogenous developmental hypoxia. It is essential that these target proteins are only degraded by the N-degron pathway under the appropriate physiological conditions.
View Article and Find Full Text PDFCharacterization of spike S1/S2 processing and entry pathways of lentiviral pseudoviruses bearing seasonal human coronaviruses NL63, 229E, and HKU1 spikes.
Microbiol Spectr
January 2025
Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Although much has been learned about the entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain less well understood. In the present study, we used 293T cell lines stably expressing angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2), which support high-level transduction of lentiviral pseudoviruses bearing spike proteins of seasonal HCoVs, HCoV-NL63, -229E, or -HKU1, respectively, to compare spike processing and virus entry pathways among these viruses. Our results showed that the entry of HCoV-NL63, -229E, and -HKU1 pseudoviruses into cells is sensitive to endosomal acidification inhibitors (chloroquine and NHCl), indicating entry via the endocytosis route.
View Article and Find Full Text PDFAngiotensin IV Receptors in the Rat Prefrontal Cortex: Neuronal Expression and NMDA Inhibition.
Biomedicines
December 2024
Department of Oral Biology, Semmelweis University, H-1089 Budapest, Hungary.
Background: N-methyl-D-aspartate type glutamate receptors (NMDARs) are fundamental to neuronal physiology and pathophysiology. The prefrontal cortex (PFC), a key region for cognitive function, is heavily implicated in neuropsychiatric disorders, positioning the modulation of its glutamatergic neurotransmission as a promising therapeutic target. Our recently published findings indicate that AT receptor activation enhances NMDAR activity in layer V pyramidal neurons of the rat PFC.
View Article and Find Full Text PDFIntegrated enzyme activities and untargeted metabolome to reveal the mechanism that allow long-term biochar-based fertilizer substitution improves soil quality and maize yield.
Environ Res
January 2025
Eco-environmental Protection Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China; Key Laboratory of Low-carbon Green Agriculture in Southeastern China, Ministry of Agriculture and Rural Affairs, Shanghai 201403, China. Electronic address:
Biochar-based fertilizer has potential benefits in improving soil quality and crop yield, but the biological mechanisms of soil microbial enzymes interacting with related metabolisms still need to be further investigated. In this study, we combined enzymology and untargeted metabolomics to investigate how biochar-based fertilizer substitution affects soil quality and crop yield by regulating soil enzymes and metabolites in dry-crop farmland. Our findings showed that biochar-based fertilizer substitution enhanced the activities of enzymes related to carbon, nitrogen, and phosphorus cycling, as well as influenced metabolite composition.
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