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Chronic Low-Level IFN-γ Expression Disrupts Mitochondrial Complex I Activity in Renal Macrophages: An Early Mechanistic Driver of Lupus Nephritis Pathogenesis.
Int J Mol Sci
December 2024
Department of Food Science and Nutrition, Kyungpook National University, Daegu 41566, Republic of Korea.
Article Synopsis
- Mitochondrial dysfunction and macrophage dysregulation are important in autoimmune diseases, but how they connect is not fully understood.
- The study focuses on the role of chronic low-level interferon-gamma (IFN-γ) using a mouse model with lupus-like symptoms, finding that this condition suppresses mitochondrial function, especially in the kidneys.
- It suggests that restoring mitochondrial function could improve macrophage activity and provide new targets for treating autoimmune diseases like lupus nephritis.
Interleukin-2-mediated NF-κB-dependent mRNA splicing modulates interferon gamma protein production.
EMBO Rep
January 2025
Department of Immunology, University of Washington, Seattle, WA, 98109, USA.
Interferon-gamma (IFNγ) is a pleiotropic cytokine produced by natural killer (NK) cells during the early infection response. IFNγ expression is tightly regulated to mount sterilizing immunity while preventing tissue pathology. Several post-transcriptional effectors dampen IFNγ expression through IFNG mRNA degradation.
View Article and Find Full Text PDFA Structural Comparison of Oral SARS-CoV-2 Drug Candidate Ibuzatrelvir Complexed with the Main Protease (M) of SARS-CoV-2 and MERS-CoV.
JACS Au
August 2024
Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Article Synopsis
- Ibuzatrelvir, a new drug by Pfizer, is in phase III clinical trials as a potential replacement for Paxlovid in treating SARS-CoV-2 and has received fast-track status from the FDA.
- It targets the viral main proteases to inhibit protein processing necessary for viral replication, and unlike Paxlovid, it does not require ritonavir to enhance its effectiveness.
- The drug also shows potential against MERS-CoV, with studies revealing that its binding mode and potency differ slightly between the two viruses, offering insights for future drug design against coronaviral infections.
Probing the formation of a hetero-dimeric membrane transport complex with dual and mutagenesis.
Chem Sci
August 2024
Department of Biochemistry, University of Alberta Edmonton Alberta Canada T6G 2H7 +1 (780) 492-3931 +1 (780) 492-3931.
The reversible association of transmembrane helices is a fundamental mechanism in how living cells convey information and respond to physiological events. The cardiac calcium transport regulator phospholamban (PLN) is an example of a single-span transmembrane protein that populates a variety of reversible and competing oligomeric states. PLN primarily forms monomers and pentamers in the membrane, where the PLN pentamer is a storage form and the PLN monomer forms a hetero-dimeric inhibitory complex with SERCA.
View Article and Find Full Text PDFDietary therapy of murine primary biliary cholangitis induces hepatocellular steatosis: A cautionary tale.
Liver Int
October 2024
Division of Rheumatology, Allergy, and Clinical Immunology, School of Medicine, University of California, Davis, California, USA.
Article Synopsis
- There is growing interest in using dietary changes, specifically a diet rich in propionate, to influence autoimmune diseases due to its connection with gut health.
- The study focused on the effects of feeding propionylated high-amylose resistant starches (HAMSP) to mice with primary biliary cholangitis, assessing immune response and liver health through various biological analyses.
- The findings reveal that long-term HAMSP intake shifted T-cell populations and caused liver fat accumulation (hepatocellular steatosis), highlighting the complex relationship between diet and autoimmune conditions.
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