Abstract Idiopathic pulmonary fibrosis (IPF) represents another progressive and devastating interstitial lung disease found across populations, with a prominent male predominance accounting for approximately 70% of cases. Regional variation in IPF-related genetic polymorphisms, especially in the Americas, Europe, and Asia, points to a hereditary basis. Family history is the main risk factor. Rare mutations may alter outcomes through gene interactions. Environmental factors such as smoking can worsen genetic risk by epigenetic mechanisms like DNA methylation. Unlike studies that focus narrowly on specific genetic variants or processes, this study integrates the genetic variation map, multi-omics regulatory networks, and the effects of environmental exposures in IPF. This links clinical decision-making and gene discovery. This study examines mechanisms, therapies, and prognoses to clarify the impact of epigenetics and genetics on disease development. It also proposes using a multi-gene risk score (MGRS) to predict outcomes and design targeted treatments. The research advances the translation of basic knowledge into therapies. Theoretical and clinical support can aid doctors treating IPF. Clinical trial number Not applicable.
Abstract Background Previous research using the Ames assay showed that licoricidin (LCD) and isoliquiritigenin (ILTG) can block mutations caused by N-methyl-N-nitrosourea (MNU) in Salmonella typhimurium (S. typhimurium) TA1535. With the aim to clarify the antimutagenic mechanism of these flavonoids, we evaluated the noncovalent interactions of test compounds (LCD, ILTG, ethidium bromide (EtBr), or Hoechst 33258) with calf thymus DNA (ctDNA) using a UV-Vis spectrophotometer and quantified the DNA adducts formed when treated with a mixture of MNU and the test compounds. Additionally, we measured the half-life of MNU and the amount of each test compound remaining in the reaction mixture. Results The spectral and thermodynamic parameters indicated considerable binding between flavonoids (LCD and ILTG) and DNA. Intercalative EtBr and the minor-groove binder Hoechst 33258 inhibited MNU-induced mutagenicity in S. typhimurium TA1535. O 6-Methylguanine (O 6-MeG) and N 3-methyladenine (N 3-MeA) were quantified in a mixture of ctDNA and the test compounds (LCD, ILTG, EtBr, and Hoechst 33258) using LC‒MS/MS. The amount of the DNA adducts decreased with increasing concentrations of the compounds. Moreover, the half-lives of MNU were similar in the presence and absence of flavonoids (LCD and ILTG). No new products were detected, and no significant changes in the flavonoids remaining in the reaction mixture were observed, indicating that LCD and ILTG did not react directly with MNU. Conclusions LCD and ILTG directly bind to DNA and suppress DNA adduct formation. However, interaction with DNA alone does not fully account for their antimutagenic activity, implying the involvement of other mechanisms.
Abstract Background Substitution of dietary saturated fat with seed oils highly enriched in n-6 polyunsaturated fatty acids (PUFAs) has been advocated as healthy strategy to offset elevated cholesterol levels. However, both n-6 as well as n-3 PUFAs, considered essential because vertebrates lack the enzymatic apparatus for their de novo synthesis, are the main source of endogenous DNA damage during the aging process due to their high oxidizability. The membrane pacemaker theory of aging is an extension to the oxidative theory of aging and postulates that higher PUFA content in membrane lipids determines the lifespan of different species. Objective We have examined whether a saturated fat-rich diet lacking the essential fatty acids versus a PUFA-rich diet differentially affects lipid profiles and membrane fatty-acid composition, as well as markers of oxidative protein and DNA damage and mitochondrial DNA (mtDNA) integrity in vivo. Methods Three-week-old male C57BL/6J mice were fed isocaloric, high-fat diets containing either coconut oil (SFA-rich) or soybean oil (PUFA-rich) for 12 weeks. Plasma and liver lipids were measured, and the fatty acid composition was analyzed in liver and erythrocyte membranes. Endogenous DNA damage was assessed using 1,N⁶-etheno-2’-deoxyadenosine (εdA) detection in blood and liver. mtDNA damage and lipid peroxidation derived protein adducts from liver were also examined. Results Mice were maintained on a SFA-rich diet for 12 weeks without exhibiting any symptoms of essential fatty acid deficiency (EFAD) as described in historical literature despite the massive synthesis of compensatory n-9 PUFAs. Furthermore, EFAD mice showed reduced levels of endogenous εdA and mtDNA damage as well as protein adducts originating from the primary n-6 PUFA lipid peroxidation product, 4-hydroxy-2-nonenal. However, some other lipid peroxidation-derived protein adducts, such as malondialdehyde and, surprisingly, 4-hydroxy-2-hexenal, were elevated on a SFA-rich diet. Conclusions A PUFA-rich diet, relative to the SFA-rich diet, is associated with increased lipid-peroxidation linked adducts and a greater degree of mtDNA damage in vivo, in parallel with membrane enrichment in n-6 PUFA. These findings provide clear evidence of the biological effects of a PUFA-rich diet on endogenous genotoxic stress.
The 48th Annual Meeting and International Conference of the Environmental Mutagen Society of India (EMSI) on 'Environmental Mutagenesis & Epigenomics in Relation to Human Health' was held at Jamshedpur Co-Operative College, in association with Kolhan University, Jharkhand, India, from January 29-31, 2026. There were 141 deliberations in total, with participation from researchers, academicians, Vice-Chancellors, and state government officials from India and eight other countries. The scientific topics, including environmental impact on humans and aquaculture, transgenerational plant protection, molecular insights into cancer research, plants with antimutagenic potential, and sustainable agriculture through the use of bio-pesticides and bio-fertilizers, broadly justified the conference theme. The molecular mechanisms of pathogenesis were discussed through lectures on signalling pathways, gene expression, and DNA damage and repair, highlighting targeted drug development. Additionally, in silico docking of synthetic drugs and nanoparticles was discussed in detail. Notably, nanotoxicology, microplastics, airborne particulate matter, and prenatal arsenic exposure were shown to have a significant impact on human health. As Jharkhand and neighbouring states depend largely on agricultural yield, discussions on the use of plant-based medicines, harnessing infection and immunity, and agricultural eco-toxicology suggested ways to protect farmers' health and the food chain from the overuse of chemicals. Altogether, the deliberations supported several Sustainable Development Goals and highlighted cost-effective agricultural modalities. These messages were disseminated to the public through local media via daily briefings. Notably, this EMSI conference provided a platform for scientific exchange that attracted administrators and pollution control regulators aimed at protecting human health by mitigating environmental exposure.
Symposium 3 of the 53rd Annual Meeting of the Japanese Environmental Mutagen and Genome Society (JEMS), entitled "Potential for Computational Genotoxicity," was held at Shujitsu University, Okayama, Japan, on December 8, 2024. The symposium discussed the application of advanced informatics technologies, such as (quantitative) structure-activity relationship ((Q)SAR) and error-corrected next-generation sequencing (ecNGS), to the field of genotoxicity within the framework of computational genotoxicity. In this symposium, we invited three scientists who are global leaders in the field of computational genotoxicity. This report summarizes the key discussions and presentations from the symposium. The organizers hope this summary will increase awareness of computational genotoxicity.
