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Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial.
Brain Commun
January 2025
Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm 17165, Sweden.
Parkinson's disease is primarily marked by mitochondrial dysfunction and metabolic abnormalities. We recently reported that the combined metabolic activators improved the immunohistochemical parameters and behavioural functions in Parkinson's disease and Alzheimer's disease animal models and the cognitive functions in Alzheimer's disease patients. These metabolic activators serve as the precursors of nicotinamide adenine dinucleotide and glutathione, and they can be used to activate mitochondrial metabolism and eventually treat mitochondrial dysfunction.
View Article and Find Full Text PDFSize effect-based improved antioxidant activity of selenium nanoparticles regulating Anti-PI3K-mTOR and Ras-MEK pathways for treating spinal cord injury to avoid hormone shock-induced immunosuppression.
J Nanobiotechnology
January 2025
Department of Orthopedics, Zhuhai Medical College (Zhuhai People's Hospital), State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Chemistry and Materials Science, Jinan University, Zhuhai, 519000, China.
Spinal cord injury (SCI) is a critical condition affecting the central nervous system that often has permanent and debilitating consequences, including secondary injuries. Oxidative damage and inflammation are critical factors in secondary pathological processes. Selenium nanoparticles have demonstrated significant antioxidative and anti-inflammatory properties via a non-immunosuppressive pathway; however, their clinical application has been limited by their inadequate stability and functionality to cross the blood-spinal cord barrier (BSCB).
View Article and Find Full Text PDFSHMT2 regulates CD8+ T cell senescence via the reactive oxygen species axis in HIV-1 infected patients on antiretroviral therapy.
EBioMedicine
January 2025
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, NHC Key Laboratory of AIDS Prevention and Treatment, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University, Shenyang, 110001, China; Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, 110001, China; Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, 110001, China. Electronic address:
Background: Although antiretroviral therapy (ART) effectively inhibits viral replication, it does not fully mitigate the immunosenescence instigated by HIV infection. Cellular metabolism regulates cellular differentiation, survival, and senescence. Serine hydroxymethyltransferase 2 (SHMT2) is the first key enzyme for the entry of serine into the mitochondria from the de novo synthesis pathway that orchestrates its conversion glutathione (GSH), a key molecule in neutralising ROS and ensuring the stability of the immune system.
View Article and Find Full Text PDFCardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection.
J Mol Cell Cardiol Plus
September 2024
O'Brien Institute Department, St Vincent's Institute of Medical Research, Victoria 3065, Australia.
Dynamin-related protein 1 (Drp1) is a mitochondrial fission protein and a viable target for cardioprotection against myocardial ischaemia-reperfusion injury. Here, we reported a novel Drp1 inhibitor (DRP1i1), delivered using a cardiac-targeted nanoparticle drug delivery system, as a more effective approach for achieving acute cardioprotection. DRP1i1 was encapsulated in cubosome nanoparticles with conjugated cardiac-homing peptides (NanoDRP1i1) and the encapsulation efficiency was 99.
View Article and Find Full Text PDFCalcineurin inhibitors (CNIs) are indispensable immunosuppressants for transplant recipients and patients with autoimmune diseases, but chronic use causes nephrotoxicity, including kidney fibrosis. Why inhibiting calcineurin, a serine/threonine phosphatase, causes kidney fibrosis remains unknown. We performed single-nucleus RNA sequencing of the kidney from a chronic CNI nephrotoxicity mouse model and found an increased proportion of injured proximal tubule cells, which exhibited altered expression of genes associated with oxidative phosphorylation, cellular senescence and fibrosis.
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