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Combined PARP14 inhibition and PD-1 blockade promotes cytotoxic T cell quiescence and modulates macrophage polarization in relapsed melanoma.
J Immunother Cancer
January 2025
Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, UK
Background: Programmed cell death 1 (PD-1) signaling blockade by immune checkpoint inhibitors (ICI) effectively restores immune surveillance to treat melanoma. However, chronic interferon-gamma (IFNγ)-induced immune homeostatic responses in melanoma cells contribute to immune evasion and acquired resistance to ICI. Poly ADP ribosyl polymerase 14 (PARP14), an IFNγ-responsive gene product, partially mediates IFNγ-driven resistance.
View Article and Find Full Text PDFIntraspecific identification and genetic diversity analysis of Paeonia lactiflora based on chloroplast genes rpoB and psbK-psbI.
Mol Biol Rep
January 2025
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People's Republic of China.
Background: Paeonia lactiflora Pall., a member of Paeoniaceae family, is a medicinal herb widely used in traditional Chinese medicine. Chloroplasts are multifunctional organelles containing distinct genetic material.
View Article and Find Full Text PDFEffect of 8-Oxo-1,-Ethenoadenine Derivatives on the Activity of RNA Polymerases from SARS-CoV-2 and .
Biochemistry (Mosc)
December 2024
National Research Centre "Kurchatov Institute", Moscow, 123182, Russia.
Bacterial and viral RNA polymerases are promising targets for the development of new transcription inhibitors. One of the potential blockers of RNA synthesis is 7,8-dihydro-8-oxo-1,-ethenoadenine (oxo-εA), a synthetic compound that combines two adenine modifications: 8-oxoadenine and 1,-ethenoadenine. In this study, we synthesized oxo-εA triphosphate (oxo-εATP) and showed that it could be incorporated by the RNA-dependent RNA polymerase of SARS-CoV-2 into synthesized RNA opposite template residues A and G in the presence of Mn ions.
View Article and Find Full Text PDFEffects of the RNA-Binding Protein Sam68 on Poly(ADP-Ribose)polymerase 1 Activity.
Biochemistry (Mosc)
December 2024
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.
Taking into account involvement of the RNA-binding proteins in regulation of activity of poly(ADP-ribose) polymerase 1 (PARP1), a key factor of DNA repair, the effect of the intrinsically disordered protein Sam68 (Src-associated substrate during mitosis of 68 kDa) on catalytic activity of this enzyme was studied. Plasmid containing coding sequence of the Sam68 protein was obtained. Using the obtained construct, conditions for the Sam68 expression in cells were optimized and procedure for protein purification was developed.
View Article and Find Full Text PDFExploiting the Achilles' Heel of Viral RNA Processing to Develop Novel Antivirals.
Viruses
December 2024
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Treatment options for viral infections are limited and viruses have proven adept at evolving resistance to many existing therapies, highlighting a significant vulnerability in our defenses. In response to this challenge, we explored the modulation of cellular RNA metabolic processes as an alternative paradigm to antiviral development. Previously, the small molecule 5342191 was identified as a potent inhibitor of HIV-1 replication by altering viral RNA accumulation at doses that minimally affect host gene expression.
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