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Palmitate potentiates the SMAD3-PAI-1 pathway by reducing nuclear GDF15 levels.
Cell Mol Life Sci
January 2025
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Unitat de Farmacologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028, Barcelona, Spain.
Nuclear growth differentiation factor 15 (GDF15) reduces the binding of the mothers' against decapentaplegic homolog (SMAD) complex to its DNA-binding elements. However, the stimuli that control this process are unknown. Here, we examined whether saturated fatty acids (FA), particularly palmitate, regulate nuclear GDF15 levels and the activation of the SMAD3 pathway in human skeletal myotubes and mouse skeletal muscle, where most insulin-stimulated glucose use occurs in the whole organism.
View Article and Find Full Text PDFFirst real-world clinical experience with [Lu]Lu-PSMA-I&T in patients with metastatic castration-resistant prostate cancer beyond VISION and TheraP criteria.
Eur J Nucl Med Mol Imaging
January 2025
Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
Purpose: To report real-world clinical experience with [Lu]Lu-PSMA-I&T targeted radionuclide therapy (TRT) in patients with metastatic castration-resistant prostate cancer (mCRPC) in a single tertiary referral university hospital.
Methods: Patients with mCRPC who were treated with [Lu]Lu-PSMA-I&T TRT as standard of care between February 2022 and August 2023 were included in this retrospective study. Patients were treated with a maximum of six cycles with a fixed activity of 7.
DEC1 deficiency promotes osteoclastic activity by augmenting NFATc1 signaling via transactivation and the Ca/calcineurin pathway.
Biochem Pharmacol
January 2025
Department of Pharmacology, Nanjing Medical University, Nanjing 211166, PR China. Electronic address:
We have previously demonstrated that DEC1 promotes osteoblast differentiation. This study aims to evaluate the impact of DEC1 knockout on osteopenic activities, such as osteoclast differentiation and the expression of bone-degrading genes. To gain mechanistic insights, we employed both in vivo and in vitro experiments, utilizing cellular and molecular approaches, including osteoclast differentiation assays and RNA-seq in combination with ChIP-seq.
View Article and Find Full Text PDFSynthesis and functional screening of novel inhibitors targeting the HDAC6 zinc finger ubiquitin-binding domain.
Eur J Med Chem
December 2024
SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium. Electronic address:
Histone deacetylase 6 (HDAC6) is a promising target for treating neurodegenerative disorders, several cancer types and viral infections. Unique among HDACs, the HDAC6 isoform possesses a zinc finger ubiquitin-binding domain (UBD) crucial for managing misfolded protein aggregates and facilitating viral infection. HDAC6 binds aggregated polyubiquitinated proteins through its UBD, mediating their transport to the aggresome and subsequent removal via autophagy.
View Article and Find Full Text PDFOral iron sulfide prevents acute alcohol intoxication by initiating the endogenous multienzymatic antioxidant defense system.
Sci Adv
January 2025
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
Acute alcohol intoxication could cause multiorgan damage, including nervous, digestive, and cardiovascular systems, and in particular, irreversible damage to the brain and liver. Emerging studies have revealed that the endogenous multienzymatic antioxidant defense system (MEAODS) plays a central role in preventing oxidative stress and other toxicological compounds produced by alcohol. However, few available drugs could quickly regulate MEAODS.
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