Alcohol use disorder (AUD) is a chronic neuropsychiatric condition that causes an increased risk of dementia and deaths worldwide. Evidence indicates that alcohol misuse can induce changes in genetic factors. Alcohol-induced DNA epigenetic modification alters brain function and contributes to AUD. Among these modifications, DNA methylation is highly implicated in AUD; however, 5-hydroxymethylation of 5-methylcytosine mediated by ten-eleven translocation (TET) enzymes produces 5-hydroxymethylcytosine (5hmC), which has emerged as a stable epigenetic mark. Recent studies have shown that 5hmC at gene promoters can influence gene expression, especially of genes related to neurotransmitter signaling, alcohol addiction, and cognition. In this review, we summarize findings of TETs-mediated 5-hydroxymethylation in AUD, with special emphasis on the brain and liver. Furthermore, we highlight the key challenges and research gaps in understanding the underlying mechanisms of TETs/5hmC-mediated epigenetic modification in AUD.
Sampath Raghul Kannan, K. Santhoshkumar, R. Tamizhselvi· Frontiers in Aging Neuroscie...· 0 citations
Introduction Streptomyces species represent an important source of bioactive natural products, yet systematic genome-guided prioritization of metabolites targeting cyclooxygenase-2 (COX-2/PTGS2) remains limited. This study aimed to investigate the biosynthetic potential of Streptomyces sp. VITGV156 (MCC 4965) using an integrated genome mining and computational drug discovery pipeline. Methods Whole-genome sequencing, functional annotation, antiSMASH v7.0.1-based biosynthetic gene cluster (BGC) prediction, LC-MS/MS metabolomic profiling, SwissADME analysis, target prediction, disease association mapping, molecular docking against PTGS2 (PDB: 5IKR), and PASS bioactivity prediction were performed to prioritize putative bioactive metabolites. Results Genome analysis identified 29 predicted biosynthetic gene clusters, including clusters associated with geosmin, ectoine, albaflavenone, hopene, coelichelin, and SapB, together with several cryptic clusters exhibiting low similarity to known pathways. LC-MS/MS metabolomic profiling provided experimental support for active secondary metabolite production under the cultivation conditions employed. Computational prioritization identified PTGS2 (COX-2) as a biologically relevant target. Molecular docking demonstrated favorable binding affinities and interaction profiles for several predicted metabolites within the PTGS2 catalytic pocket. PASS analysis further suggested potential anticancer-related biological activities that require experimental validation. Discussion These findings demonstrate the utility of integrating genome mining, metabolomic profiling, and computational drug discovery for prioritizing natural-product candidates. Streptomyces sp. VITGV156 (MCC 4965) represents a promising source of biosynthetic diversity and provides a genome-guided framework for identifying putative COX-2-targeting natural products for future experimental validation rather than confirming metabolite production or biological activity.
Veilumuthu Pattapulavar, Saranyadevi Subburaj, Sathiyabama Ramanujam et al.· Frontiers in Bioinformatics· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
