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Altered lipid homeostasis and autophagy precipitate diffuse alveolar hemorrhage in murine lupus.
Autophagy Rep
July 2024
Division of Rheumatology, Allergy, & Clinical Immunology, Gainesville, FL 32610.
Abnormal autophagy regulation is implicated in lupus and other autoimmune diseases. We investigated autophagy in the murine pristane-induced lupus model. Pristane causes monocyte/macrophage-mediated endoplasmic reticulum (ER) stress in lung endothelial cells and diffuse alveolar hemorrhage (DAH) indistinguishable from DAH in lupus patients.
View Article and Find Full Text PDFEzetimibe Anticancer Activity via the p53/Mdm2 Pathway.
Biomedicines
January 2025
Department of Life & Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Cnr. Pioneer and Christiaan de Wet Roads, B2-010 Calabash Building, Florida, Johannesburg 1710, South Africa.
Background: Ezetimibe is used to treat cardiovascular disease as it blocks the sterol transporter Niemann-Pick C1-Like 1 (NPC1CL1) protein. However, recent evidence indicates that Ezetimibe inhibits several cancers indirectly by reducing circulating cholesterol or via specific signalling pathways.
Methods And Results: Our in silico studies indicate that Ezetimibe binds to the Tp53 binding domain in Mdm2, forming a more thermodynamically stable complex than nutlin3a.
Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer.
Nat Immunol
January 2025
Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Maturation of conventional dendritic cells (cDCs) is crucial for maintaining tolerogenic safeguards against auto-immunity and for promoting immunogenic responses to pathogens and cancer. The subcellular mechanism for cDC maturation remains poorly defined. We show that cDCs mature by leveraging an internal reservoir of cholesterol (harnessed from extracellular cell debris and generated by de novo synthesis) to assemble lipid nanodomains on cell surfaces of maturing cDCs, enhance expression of maturation markers and stabilize immune receptor signaling.
View Article and Find Full Text PDFCase Report: Two years of compassionate use with Olipudase-alfa in a child with neurovisceral acid sphingomyelinase deficiency.
Front Pediatr
January 2025
Division of Metabolic Diseases and Hepatology, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.
Acid sphingomyelinase deficiency (ASMD) is a rare, progressive lysosomal storage disorder resulting from a deficiency in acid sphingomyelinase, leading to sphingomyelin accumulation and multi-organ damage. ASMD presents a broad phenotypic spectrum with a continuum of severity, making it challenging to predict the phenotype in very young children and differentiate between acute and chronic neurovisceral disease. No disease-specific treatments existed for ASMD.
View Article and Find Full Text PDFNiemann-Pick Type C Disease: From Variant of Uncertain Significance to Pathogenic Variant.
Mov Disord Clin Pract
January 2025
Movement Disorders Clinic, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
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