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Itaconate mechanism of action and dissimilation in .
Proc Natl Acad Sci U S A
January 2025
Centre for Tuberculosis Research, Tuberculosis Research Laboratory, Translational Health Science and Technology Institute, National Capital Region Biotech Science Cluster 3rd Milestone, Faridabad, Haryana 121001, India.
Itaconate, an abundant metabolite produced by macrophages upon interferon-γ stimulation, possesses both antibacterial and immunomodulatory properties. Despite its crucial role in immunity and antimicrobial control, its mechanism of action and dissimilation are poorly understood. Here, we demonstrate that infection of mice with increases itaconate levels in lung tissues.
View Article and Find Full Text PDFA single outer-sphere amino-acid substitution turns on the NO reactivity of a hemerythrin-like protein.
Chem Sci
January 2025
Department of Chemical Physiology and Biochemistry, School of Medicine, Oregon Health & Science University 3181 SW Sam Jackson Park Road Portland Oregon 97239 USA
Mycobacterial hemerythrin-like proteins (HLPs) are important for the survival of pathogens in macrophages. Their molecular mechanisms of function remain poorly defined but recent studies point to their possible role in nitric oxide (NO) scavenging. Unlike any nonheme diiron protein studied so far, the diferric HLP from (-HLP) reacts with NO in a multistep fashion to consume four NO molecules per diiron center.
View Article and Find Full Text PDFFhaA plays a key role in mycobacterial polar elongation and asymmetric growth.
mBio
January 2025
Analytical Biochemistry and Proteomics Unit, Instituto de Investigaciones Biológicas Clemente Estable and Institut Pasteur de Montevideo, Montevideo, Uruguay.
Unlabelled: Mycobacteria, including pathogens like , exhibit unique growth patterns and cell envelope structures that challenge our understanding of bacterial physiology. This study sheds light on FhaA, a conserved protein in , revealing its pivotal role in coordinating cell envelope biogenesis and asymmetric growth. The elucidation of the FhaA interactome in living mycobacterial cells reveals its participation in the protein network orchestrating cell envelope biogenesis and cell elongation/division.
View Article and Find Full Text PDFThe immune exhaustion paradox: activated functionality during chronic bacterial infections.
J Infect Dev Ctries
December 2024
Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
Co-inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), known as immune checkpoints, regulate the activity of T and myeloid cells during chronic viral infections and are well-established for their roles in cancer therapy. However, their involvement in chronic bacterial infections, particularly those caused by pathogens endemic to developing countries, such as Mycobacterium tuberculosis (Mtb), remains incompletely understood. Cytokine microenvironment determines the expression of co-inhibitory molecules in tuberculosis: Results indicate that the cytokine IL-12, in the presence of Mtb antigens, can enhance the expression of co-inhibitory molecules while preserving the effector and memory phenotypes of CD4+ T cells.
View Article and Find Full Text PDFPerformance evaluation of the LIOFeron®TB/LTBI IGRA for screening of paediatric LTBI and tuberculosis.
Eur J Pediatr
January 2025
Infectious Diseases Unit, Department of Health Sciences, Anna Meyer Children's University Hospital, University of Florence, Florence, Italy.
Purpose: High-accuracy diagnostic screening tests for Mycobacterium tuberculosis (MTB) infection are required, primarily to detect patients with latent infections (LTBIs) in order to avoid their progression to active tuberculosis disease. The performance of the novel IGRA LIOFeron®TB/LTBI was evaluated in children. The originality of this test is the new MTB antigen contained (L-alanine dehydrogenase), identified as a tool to differentiate active TB from LTBI infection.
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