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Cytotoxic DNAs, methylation, histones and histones binding proteins are speculated to induce DNA sensors. Under stressed condition, the antigenic patterns, PAMPs and DAMPs, trigger the hyperactive innate response through DNA, DNA-RNA hybrids, oligonucleotides, histones and mtDNA to initiate cGAMP-STING-IFN I cascade. HSV -1&2, HIV, Varicella- Zoster virus, Polyomavirus, Cytomegalovirus, and KSHV negatively regulate the STING-MAVS-TBK-1/1KKE pathway.

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Acute kidney injury (AKI) is one of the most serious and common complications in the course of sepsis, known for its poor prognosis and high mortality rate. Recently, ferroptosis, as a newly discovered regulatory cell death, might be closely associated with the progression of AKI. METTL14 is a writer of RNA m6A, an abundant epigenetic modification in transcriptome with broad function.

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Organophosphorus pesticides (OPs) are widely used in agricultural production, posing a great threat to human health and the environment. Given that different OPs present different toxicology and toxicities, identifying individual pesticide residues becomes important for assessing food safety and environmental implications. In this work, a kinetics difference-driven analyte hydrolysis strategy is proposed for the first time and validated to identify -nitrophenyl pesticides by developing an organophosphorus hydrolase-like nanozyme-coded sensor array.

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Objective: To assess CXC chemokine receptor 5 (CXCR5) circulating DNA methylation differences in autoimmune rheumatic diseases and their relation with clinical features.

Methods: Targeted methylation sequencing was performed using peripheral blood from 164 rheumatoid arthritis (RA), 30 systemic lupus erythematosus (SLE), 30 ankylosing spondylitis (AS), 30 psoriatic arthritis (PsA), 24 Sjögren's syndrome (SS) patients, and 30 healthy controls (HC).

Results: Significant differences in CXCR5 cg19599951 methylation were found between RA and HC, as well as AS and SLE.

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Discovery of Novel Spirocyclic MAT2A Inhibitors Demonstrating High In Vivo Efficacy in MTAP-Null Xenograft Models.

J Med Chem

January 2025

Medicinal Chemistry Department, Shanghai Haiyan Pharmaceutical Technology Co., Ltd., Pudong New Area, Shanghai 201203, China.

Synthetic lethality offers a robust strategy for discovering the next generation of precision medicine therapies tailored for molecularly defined patient populations. MAT2A inhibition is synthetically lethal in several cancers that exhibit a homozygous deletion of -methyl-5'-thioadenosine phosphorylase (MTAP). Herein, we report the identification of novel MAT2A inhibitors featuring a spiral ring to circumvent the C-N atropisomeric chirality utilizing structure-based drug design.

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