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The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation.
Transpl Int
January 2025
Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
An overview is provided of the evolution of strategies towards xenotransplantation during the past almost 40 years, focusing on advances in gene-editing of the organ-source pigs, pre-transplant treatment of the recipient, immunosuppressive protocols, and adjunctive therapy. Despite initial challenges, including hyperacute rejection resulting from natural (preformed) antibody binding and complement activation, significant progress has been made through gene editing of the organ-source pigs and refinement of immunosuppressive regimens. Major steps were the identification and deletion of expression of the three known glycan xenoantigens on pig vascular endothelial cells, the transgenic expression of human "protective" proteins, e.
View Article and Find Full Text PDFPegcetacoplan for the Treatment of Paediatric C3 Glomerulonephritis: A Case Report.
Nephrology (Carlton)
February 2025
Phoenix Children's Hospital-Thomas Campus, Phoenix, Arizona, USA.
Complement 3 glomerulonephritis (C3GN) is a rare glomerular disease involving dysregulation of the complement system. We describe our experience using pegcetacoplan, an inhibitor of C3 and its activation fragment, C3b, for treatment-resistant C3GN in a 9-year-old boy referred for evaluation of refractory membranoproliferative glomerulonephritis. Despite treatment with intense immunosuppression (high-dose steroids, mycophenolate mofetil and calcineurin inhibitor), he continued to have high disease activity with low C3 levels (35 mg/dL), hypertension, symptomatic oedema, anaemia, and nephrotic-range proteinuria (e.
View Article and Find Full Text PDFComplement-Mediated Hemolytic Uremic Syndrome Due to MCP/CD46 Mutation: A Case Report.
J Investig Med High Impact Case Rep
January 2025
Marshall University, Huntington, WV, USA.
Thrombotic microangiopathy (TMA) is a severe condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ damage, often involving the kidneys. Complement-mediated hemolytic uremic syndrome (cHUS), a rare form of TMA, arises from dysregulated alternative complement pathway activation, frequently due to genetic mutations. We report the case of a 23-year-old male presenting with TMA secondary to a heterozygous mutation in the membrane cofactor protein (MCP/CD46) gene.
View Article and Find Full Text PDFPhysical Exercise Decreases Complement-Mediated Synaptic Loss and Protects Against Cognitive Impairment by Inhibiting Microglial Tmem9-ATP6V0D1 in Alzheimer's Disease.
Aging Cell
January 2025
Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Physical exercise is known to slow synaptic neurodegeneration and cognitive aging in Alzheimer's disease (AD). The benefits of physical exercise are related to reduced amyloid beta (Aβ) deposition and increased synaptic plasticity. Yet little is known about the mechanisms that mediate these effects.
View Article and Find Full Text PDFMechanisms of wogonoside in the treatment of atherosclerosis based on network pharmacology, molecular docking, and experimental validation.
BMC Complement Med Ther
January 2025
Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
Background: Atherosclerosis serves as the fundamental pathology for a variety of cardiovascular disorders, with its pathogenesis being closely tied to the complex interplay among lipid metabolism, oxidative stress, and inflammation. Wogonoside is a natural flavonoid extracted from Scutellaria baicalensis with a variety of biological activities, including anti-inflammatory, hypolipidemic, and cardiac function improvement properties. Despite these known effects, the specific role of wogonoside in the context of atherosclerosis remains to be elucidated.
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