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Discovery of PRMT5 N-Terminal TIM Barrel Ligands from Machine-Learning-Based Virtual Screening.
ACS Omega
January 2025
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States.
Protein arginine methyltransferase 5 (PRMT5), which symmetrically dimethylates cytosolic and nuclear proteins, has been demonstrated as an important cancer therapeutic target. In recent years, many advanced achievements in PRMT5 inhibitor development have been made. Most PRMT5 inhibitors in the clinical trial focus on targeting the C-terminal catalytic domain, whereas developing small molecules to interrupt the PRMT5/pICLn (methylosome subunit) protein-protein interface is also of great importance for inhibiting PRMT5.
View Article and Find Full Text PDFK7 channels modulate tension and calcium signalling in mouse corpus cavernosum.
Am J Physiol Cell Physiol
January 2025
Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, Ireland.
Adrenergic stimulation induces contractions in the corpus cavernosum smooth muscle (CCSM) that are important in maintaining penile flaccidity. The aim of this study was to investigate the role of K7 channels in regulating contractions and their underlying Ca signals in mouse CCSM. Quantitative PCR revealed transcriptional expression of KCNQ1 and KCNQ3-5 genes in whole CCSM, with KCNQ5 as the most highly transcribed K7 encoding gene.
View Article and Find Full Text PDFExercise-induced cytosolic calcium oscillations: mechanisms and modulation of T-cell function.
Biochem Biophys Res Commun
January 2025
School of Physical Education, China University of Geosciences (Wuhan), Wuhan, China. Electronic address:
This study investigated time-dependent changes in intracellular Ca⁺ levels in T cells, regulatory mechanisms, and functional effects after acute exercise. Male C57BL/6 mice were assigned to control and exercise groups, with the latter sacrificed at different intervals post-exercise. Murine splenic lymphocytes were isolated, and cytosolic Ca⁺ levels were measured using Fluo-3/AM.
View Article and Find Full Text PDFAnti-inflammatory and antioxidant properties of Camellia sinensis L. extract as a potential therapeutic for atopic dermatitis through NF-κB pathway inhibition.
Sci Rep
January 2025
Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju, 52828, Republic of Korea.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation and excessive cytokine production. This study aimed to explore the potential of Camellia sinensis L. water extract (CSE) as a treatment for AD by the impact of CSE on inflammatory responses in keratinocytes, particularly concerning the production of inflammatory cytokines and the modulation of signaling pathways relevant to AD pathogenesis.
View Article and Find Full Text PDFAberrant fumarate metabolism links interferon release in diffuse systemic sclerosis.
J Dermatol Sci
January 2025
Biosciences Department, Durham University, Durham, United Kingdom. Electronic address:
Background: Systemic Sclerosis (SSc) is an idiopathic rheumatic inflammatory disease that is characterised by inflammation and skin fibrosis. Type I interferon is significantly elevated in the disease.
Objective: The objective of this study is to determine the role of the TCA cycle metabolite fumarate in SSc.
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