Nucleosides and purine nucleotides serve as transmitter and modulator agents that extend their functions beyond the cell. In this context, purinergic signaling plays a crucial role in regulating energy homeostasis and modulating metabolic alterations in tumor cells. Therefore, it is essential to consider the pharmacological targeting of purinergic receptors (PUR), which encompass the expression and inhibition of P1 receptors (metabotropic adenosine receptors) as well as P2 receptors (extracellular ATP/ADP) comprising P2X and P2Y receptors. Thus, the pharmacological interaction between inhibitors (such as RNA, monoclonal antibodies, and small molecules) and PUR represents a key aspect in facilitating the development of therapeutic interventions. Moreover, this review explores recent advancements in pharmacological inhibitors and the regulation of innate and adaptive immunity of PUR, specifically in relation to immunological and inflammatory responses. These responses encompass the release of pro-inflammatory cytokines (PIC), the production of reactive oxygen and nitrogen species (ROS and RNS), the regulation of T cells, and the activation of inflammasomes in all human leukocytes.
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http://dx.doi.org/10.1007/s11302-023-09966-7 | DOI Listing |
Free Radic Biol Med
January 2025
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi-110067. Electronic address:
Iron accumulation and mitochondrial dysfunction in astroglia are reported in Parkinson's disease (PD). Astroglia control iron availability in neurons in which dopamine (DA) synthesis is affected in PD. Despite their intimate relationship the role of DA in astroglial iron homeostasis is limited.
View Article and Find Full Text PDFStructure
January 2025
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. Electronic address:
High-risk human papillomavirus E6 oncoprotein is a model system for the recognition and degradation of cellular p53 tumor suppressor protein. There remains a gap in the understanding of the ubiquitin transfer reaction, including placement of the E6AP catalytic HECT domain of the ligase concerning the p53 substrate and how E6 itself is protected from ubiquitination. We determined the cryoelectron microscopy (cryo-EM) structure of the E6AP/E6/p53 complex, related the structure to in vivo modeling of the tri-molecular complex, and identified structural interactions associated with activation of the ubiquitin ligase function.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China; Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China. Electronic address:
Bacterial adaptive immunity, driven by CRISPR-Cas systems, protects against foreign nucleic acids from mobile genetic elements (MGEs), like bacteriophages. The type I-E CRISPR-Cas system employs the Cascade (CRISPR-associated complex for antiviral defense) complex for target DNA cleavage, guided by crRNA. Anti-CRISPR (Acr) proteins, such as AcrIE7, counteract this defense by inhibiting Cascade activity.
View Article and Find Full Text PDFJ Psychiatr Res
January 2025
Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen university, 510080, Guangzhou, China; Guangdong Engineering Technology Research Center of Nutrition Translation, 510080, Guangzhou, China. Electronic address:
The association between childhood trauma (CT), stressful life events (SLE) and the onset and severity of major depressive disorder (MDD) has not been extensively studied. This study aimed to investigate the separate and combined association of CT and SLE with the onset and severity of MDD. A total of 503 patients with MDD and 503 controls were included.
View Article and Find Full Text PDFMicrobiol Spectr
January 2025
Department of Pharmacology, Showa University Graduate School of Medicine, Shinagawa, Tokyo, Japan.
Unlabelled: The concept of genome-microbiome interactions, in which the microenvironment determined by host genetic polymorphisms regulates the local microbiota, is important in the pathogenesis of human disease. In otolaryngology, the resident bacterial microbiota is reportedly altered in non-infectious ear diseases, such as otitis media pearls and exudative otitis media. We hypothesized that a single-nucleotide polymorphism in the ATP-binding cassette sub-family C member 11 () gene, which determines earwax properties, regulates the ear canal microbiota.
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