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Conditional Deletion of Gremlin-1 in Cathepsin K-expressing Mature Osteoclasts Altered the Skeletal Response to Calcium Depletion in Sex-Dependent Manner.
Calcif Tissue Int
January 2025
Musculoskeletal Disease Center (151), Jerry L. Pettis Memorial VA Medical Center, VA Loma Linda Healthcare System, 11201 Benton Street, Loma Linda, CA, 92357, USA.
This study assessed the novel concept that osteoclast-derived Grem1 has regulatory functions in the skeletal response to calcium stress using an osteoclastic Grem1 conditional knockout (cKO) mouse model. The calcium stress was initiated by feeding cKO mutants and wildtype (WT) littermates a calcium-deficient diet for 2 weeks. Deletion of Grem1 in mature osteoclasts did not affect developmental bone growth nor basal bone turnover.
View Article and Find Full Text PDFRevealing the Immune Response of Gyllenhal to Entomopathogenic Fungi Infection Through Integrative Analyses of Transcriptomics and Metabolomics.
Insects
November 2024
School of Agriculture, Ningxia University, Yinchuan 750021, China.
In this study, we selected , one of the primary insect pests of alfalfa, as the experimental insect and infected it with . Transcriptomic and metabolomic analyses were conducted to explore alterations in gene expression and metabolic processes in at 48, 96, and 144 h post infection with . The transcriptomic analysis unveiled that infection boosted immune responses in tubercula, affecting carbohydrate metabolism, cytochrome P450 activity, lysosome function, apoptosis regulation, phagosome formation, glutathione metabolism, amino acid metabolism, and pathogen response pathways.
View Article and Find Full Text PDFHuman intraepithelial mast cell differentiation and effector function are directed by TGF-β signaling.
J Clin Invest
January 2025
Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Mast cells (MCs) expressing a distinctive protease phenotype (MCTs) selectively expand within the epithelium of human mucosal tissues during type 2 (T2) inflammation. While MCTs are phenotypically distinct from subepithelial MCs (MCTCs), signals driving human MCT differentiation and this subset's contribution to inflammation remain unexplored. Here, we have identified TGF-β as a key driver of the MCT transcriptome in nasal polyps.
View Article and Find Full Text PDFTargeted demethylation of cathepsin D via epigenome editing rescues pathology in Alzheimer's disease mouse model.
Theranostics
January 2025
Laboratory of Molecular Genetics, College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea.
Cathepsin D (Ctsd) has emerged as a promising therapeutic target for Alzheimer's disease (AD) due to its role in degrading intracellular amyloid beta (Aβ). Enhancing Ctsd activity could reduce Aβ42 accumulation and restore the Aβ42/40 ratio, offering a potential AD treatment strategy. This study explored Ctsd demethylation in AD mouse models using dCas9-Tet1-mediated epigenome editing.
View Article and Find Full Text PDFInhibition of intracellular versus extracellular cathepsin D differentially alters the liver lipidome of mice with metabolic dysfunction-associated steatohepatitis.
FEBS J
December 2024
Department of Genetics and Cell Biology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, The Netherlands.
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) progressing to metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatic inflammation, has significantly increased in recent years due to unhealthy dietary practices and sedentary lifestyles. Cathepsin D (CTSD), a lysosomal protease involved in lipid homeostasis, is linked to abnormal lipid metabolism and inflammation in MASH. Although primarily intracellular, CTSD can be secreted extracellularly.
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