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Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of Erythroferrone in Anemic Rats with Chronic Kidney Disease and Chemotherapy-Induced Anemia: An Early Biomarker for Hemoglobin Response and rHuEPO Hyporesponsiveness.
ACS Pharmacol Transl Sci
January 2025
Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmacy, The Chinese University of Hong Kong, Shatin 999077, Hong Kong SAR, P. R. China.
Erythroferrone (ERFE) has emerged as a potential biomarker for the erythropoiesis response following recombinant human erythropoietin (rHuEPO) treatment. While the association between ERFE and hemoglobin (HGB) response to rHuEPO is well-established in nonanemic conditions, such correlation and ERFE kinetics in anemic states remain unclear. We employed two rat models of anemia, chronic kidney disease (CKD) anemia and chemotherapy-induced anemia (CIA), to determine ERFE kinetics and its correlation with HGB responses after rHuEPO administration.
View Article and Find Full Text PDFIntranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity.
Commun Biol
January 2025
CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Lyon, France.
We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants.
View Article and Find Full Text PDFUnderstanding cataract development in axial myopia: The contribution of oxidative stress and related pathways.
Redox Biol
January 2025
Department of Ophthalmology, Kornel Gibiński University Clinical Center, Medical University of Silesia, Katowice, Poland; Department of Ophthalmology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland; GlaucoTech Co, Katowice, Poland.
Myopia is an evolving global health challenge, with estimates suggesting that by 2050 it will affect half of the world's population, becoming the leading cause of irreversible vision loss. Moreover, myopia can lead to various complications, including the earlier onset of cataracts. Given the progressive aging of the population and the increase in life expectancy, this will contribute to a rising demand for cataract surgery, posing an additional challenge for healthcare systems.
View Article and Find Full Text PDFInduction of Antigen-Specific Tolerance in a Multiple Sclerosis Model without Broad Immunosuppression.
ACS Nano
January 2025
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Multiple sclerosis (MS) is a severe autoimmune disorder that wreaks havoc on the central nervous system, leading to a spectrum of motor and cognitive impairments. There is no cure, and current treatment strategies rely on broad immunosuppression, leaving patients vulnerable to infections. To address this problem, our approach aims to induce antigen-specific tolerance, a much-needed shift in MS therapy.
View Article and Find Full Text PDFRegulatory dynamics of Sch9 in response to cytosolic acidification: From spatial reconfiguration to cellular adaptation to stresses.
iScience
January 2025
Department of Biology, Graduate School of Science, Chiba University, Chiba 263-8522, Japan.
The regulation of cellular metabolism is crucial for cell survival, with Sch9 in serving a key role as a substrate of TORC1. Sch9 localizes to the vacuolar membrane through binding to PI(3,5)P, which is necessary for TORC1-dependent phosphorylation. This study demonstrates that cytosolic pH regulates Sch9 localization.
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