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Alzheimers Dement

December 2024

AriBio Co., Ltd., Seongnam, Korea, Republic of (South).

Background: AR1001 is a specific inhibitor of phosphodiesterase-5 (PDE5), which degrades cyclic guanosine monophosphate (cGMP). cGMP/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling, which is critical for learning and memory processes, is disturbed in Alzheimer's disease (AD). AR1001 at the oral dose of 30 mg QD is currently in a global Phase 3 clinical trial in early AD patients (NCT05531526).

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Background: There are no cures for Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by elevation of beta-amyloid and tau proteins besides neuronal death and causing cognitive impairment. Phosphodiesterase 5 (PDE5) is a cyclic guanosine monophosphate-degrading enzyme involved in numerous biological pathways including those relevant to memory formation. PDE5 inhibition offers the potential to attenuate AD progression by acting at the downstream level of beta-amyloid and tau elevation.

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Structure-based method for the discovery of selective inhibitors of PED 5 in erectile dysfunction therapy from the Pacific oyster peptides (Crassostrea gigas): Peptidomic analysis, molecular docking, and activity validation.

Int J Biol Macromol

January 2025

Center for Mitochondria and Healthy Aging, School of Life Sciences, Yantai University, Yantai 264005, China; College of Life Sciences, Yantai University, Yantai 264005, Shandong, China. Electronic address:

Erectile dysfunction (ED) is a male sexual disorder mainly caused by a reduction in the cellular concentration of cyclic guanosine monophosphate (cGMP), which is degraded by phosphodiesterase type-5 (PDE-5). Oyster protein (OP) and its hydrolysates have been used for centuries to address male erectile dysfunction, however the mechanisms and evidence supporting their efficacy remain unclear. In this study, OP was hydrolyzed using trypsin to produce peptides that inhibit PDE-5.

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Antinociceptive Potential of L. Bark Extract and Caffeic Acid: Insights into Pain Modulation Pathways.

Pharmaceuticals (Basel)

December 2024

Laboratory of Pharmacology and Molecular Chemistry, Department of Chemical Biology, Regional University of Cariri (URCA), Rua Coronel Antônio Luis 1161, Pimenta, Crato 63105-000, Ceará, Brazil.

This study evaluated the antinociceptive effect of the L. bark extract (HEXA) and its primary component, caffeic acid (CA), through in vivo assays. : The antinociceptive properties were assessed using abdominal writhing, hot plate, and Von Frey tests.

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Inhalable nanovesicles loaded with a STING agonist enhance CAR-T cell activity against solid tumors in the lung.

Nat Commun

January 2025

Center for Infection and Immunity, Guangdong Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China.

Suppression of chimeric antigen receptor-modified T (CAR-T) cells by the immunosuppressive tumor microenvironment remains a major barrier to their efficacy against solid tumors. To address this, we develop an anti-PD-L1-expressing nanovesicle loaded with the STING agonist cGAMP (aPD-L1 NVs@cGAMP) to remodel the tumor microenvironment and thereby enhance CAR-T cell activity. Following pulmonary delivery, the nanovesicles rapidly accumulate in the lung and selectively deliver STING agonists to PD-L1-overexpressing cells via the PD-1/PD-L1 interaction.

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