Caspase-8 is a novel modulator of Homologous Recombination Repair in response to ionizing radiations in glioblastoma.

Polystyrene microplastics exacerbate experimental chronic kidney disease via inflammatory and oxidative pathways involving NF-κB, ERK/p38 MAPK, and sirtuin-1.

Dual cascade signal amplification lights up G4 dimers for fluorescent detection of DNA repair enzyme FEN1.

Lactate metabolism inhibition disrupts goat oocyte meiosis via H3K18la-mediated epigenetic dysregulation.

The properties of Ocicmum gratissimum aqueous extract against ultraviolet-C-induced inflammation.

Individual differences in the effects of ionizing radiation on humans remain poorly understood. Although studies on atomic bomb survivors have demonstrated that the hemizygous glycophorin A (GPA) gene mutant fraction (GPA Mf) in erythrocytes increases significantly with increasing radiation dose, there are large individual differences in the GPA Mf. Persistent GPA mutations are believed to be derived from mutations in long-lived hematopoietic stem cells (HSCs), and genetic background related to DNA repair may contribute to individual differences in HSC mutational potential after radiation exposure. In this study, we investigated three single-nucleotide polymorphisms (SNPs) in ERCC5 that play an important role in nucleotide excision repair (NER) of DNA damage caused by radiation exposure and are involved in cancer susceptibility. We found that these SNPs affect the relationship between radiation exposure and GPA Mf in erythrocytes and identified a highly significant interaction between radiation dose and one SNP (rs751402), located 2 kb upstream of ERCC5 (P = 9.3 × 10-6). This suggests that the radiation dose response of GPA Mf is partly influenced by the genotype of ERCC5. Furthermore, the slope of the GPA Mf dose-response curve was significantly higher in the cancer group than in the cancer-free group among Hiroshima survivors whose rs751402 genotype was the major homozygote. These findings suggest that ERCC5 may play a crucial role in the individual differences observed in HSC somatic gene mutability, as well as in cancer susceptibility after radiation exposure.

DNA damage repair is vital for maintaining genetic stability and integrity of cells that encounter DNA-damaging agents. So far, a series of multifunctional proteins and long noncoding RNAs (lncRNAs) have been demonstrated to participate in the DNA damage response (DDR). However, our current understanding of detailed mechanisms of DNA damage repair remains limited. Herein, we report that lncRNA EGFR-AS1 is functionally involved in DDR in both non-small-cell lung cancer cells and noncancerous cells. Using DNA repair reporter, we found that EGFR-AS1 overexpression significantly enhances the efficiency of both the classical nonhomologous end-joining and homologous recombination pathways. Through the lncRNA interactome, we identified a set of DNA repair factors, including the canonical DNA damage sensor PARP1 and NAD+ supplier NMNAT1. Upon DNA damage, DNA-activated PARP1 binds to EGFR-AS1 and forms a ternary complex with NMNAT1, promoting NAD+ utilization and poly(ADP-ribosyl)ation (PARylation) of PARP1. Additionally, EGFR-AS1 also facilitates displacing PARP1 from the sites of damaged DNA. Our findings demonstrate a lncRNA-associated PARP1 activation and displacement in DDR and highlight the potential of EGFR-AS1 as a target for cancer therapy.

Investigating penthiopyrad's potential toxicity on male reproductive health via in vitro models and computational network toxicology and docking studies.

Targeting drug-resistant E. coli with quinoline-thiazolidinone derivatives: A new avenue for combating antibacterial resistance from molecular design to mechanistic action.

Epitranscriptomics, a rapidly evolving field mainly driven by massive parallel sequencing technologies, explores post-transcriptional RNA modifications. N 6-methyladenosine (m6A) has emerged as the most prominent and dynamically regulated modification in human mRNAs, being implicated in the regulation of diverse biological processes, including spermatogenesis, heat shock response, ultraviolet-induced DNA damage response and maternal mRNA clearance. Despite the recognized significance of m6A in mRNA regulation, limited studies have focused on the targeted and efficient manipulation of this modification in mRNAs. Here, we present Dem6A-Vec, an "all-in-one" plasmid vector designed for site-specific m6A demethylation in human mRNAs. Dem6A-Vec integrates the expression of a catalytically inactive RfxCas13d fused to the m6A demethylase ALKBH5 and a U6-driven customizable guide RNA in a single construct, simplifying experimental workflows and enhancing targeting efficiency. Using nanopore direct RNA sequencing, we identify high-confident m6A sites in HeLa cells, which serve as targets for Dem6A-Vec. We validate the targeted demethylation of m6A sites in the EEF2 and RRAGA genes using the established SELECT-qPCR method, confirming the impacts on mRNA stability and highlighting the tool's precision and versatility. The presented approach is implemented in multiple mRNA sites with diverse methylation stoichiometries, underscoring its adaptability to various transcriptomic contexts. This study provides a robust and scalable method for investigating the functional roles of m6A modifications, offering a transformative platform for advancing epitranscriptomic research and potential therapeutic applications.

Crosstalk between ApoE-expressing cells and genotoxic stress in the mouse brain.

circSHOC1-SLC25A3 promotes 2-naphthylamine-induced DNA damage in bronchial epithelial cells via activation of oxidative stress.

Micro (nano)-plastics (MPs/NPs) are ubiquitously detected in human samples: stool, placenta, breastmilk, testes and semen, liver, lung, and blood, with their detailed toxicological profile still emerging. Numerous scientific studies are increasingly being conducted towards understanding possible deleterious effects of MPs/NPs on human, animal, plant, and environmental health. MPs/NPs rarely biodegrade, have small particle sizes, and are positively charged-features that make them dangerous to cells. They are capable of inducing oxidative stress, genotoxicity, immunological response, alteration in cellular membrane and cytoarchiture. The ability for MPs/NPs to induce DNA damage and genotoxicity may enhance genome instability, the hallmark of cancer and genetic disease syndrome. This review focused on determining the sensitivity of various biomarkers utilized to assess the DNA damage and genotoxicity potentials of MPs/NPs, the bioindicators used as models (invertebrates, vertebrates, cell lines/primary cells and plants), and the mechanisms of MPs/NPs-induced genotoxicity and DNA damage. The nature/type and size of the MP/NP polymers, concentration, and duration of exposure are determining factors considered in the DNA damage and genotoxicity assessment of MPs/NPs. Also, somatic and germ-line cells are susceptible to the genotoxic effects of MPs/NPs. Single and double DNA strand breaks assessed using the comet assay are the most used biomarker of DNA damage, while chromosome aberration is the least used. Others are sperm morphology assay, micronucleus assay, and toxicogenomics. The mechanisms of MPs/NPs-induced DNA damage include generation of free radicals and oxidative stress, induction of deleterious inflammatory cells, down-regulation of transcriptional genes related to apoptotic expressions, and increased DNA fragmentation in cells and tissues. Further studies are required to unequivocally confirm MPs/NPs as genotoxins, mutagens, and/or carcinogens.

Circular RNAs accumulate in aging human placental tissue and in stillbirth, leading to DNA damage and cellular senescence.

Targeting DNA damage: A natural product-based strategy for inhibiting cancer progression.

DNA damage through endogenous and environmental toxicants is a constant threat to both a human's ability to pass on intact genetic information to its offspring as well as in somatic cells for its own survival. To counter these threats posed by DNA damage, cells have evolved a series of highly choreographed mechanisms, collectively defined as the DNA-damage response (DDR), to sense DNA lesions, signal their presence, and mediate their repair. Thus, regular DDR signaling cascades are vital to prevent the initiation and progression of many human diseases including cancer. Consequently, quantitative assessment of DNA damage and response became an important biomarker for assessment of human health and disease risk in biomonitoring studies. However, most quantitative DNA damage biomarker techniques require dissolution of the nuclear architecture and hence loss of spatial information. Laser scanning confocal immunofluorescence microscopy (LSCIM) of three-dimensionally preserved nuclei can be, quantitative and maintain the spatial information. Here we describe the experimental protocols to quantify individual key events of the DDR cascade in three-dimensionally preserved nuclei by LSCIM with high resolution, using the simultaneous detection of Rad50 as well as phosphorylated H2AX and ATM and in somatic and germ cells as an example.

Interplay between lung and intestine in responses to diesel exhaust particles: Contrasting intestinal effects of cleared and swallowed particles with lung-mediated effects using an in vitro approach.

Persistent DNA damage leads to genomic instability, a driver of various illnesses. This points to the importance of the detection of DNA damage. In the last few decades, Drosophila melanogaster has emerged as a powerful alternative model system to animal experimentation in toxicological research, including genotoxicity studies. Several genetic and molecular methods have been developed to detect DNA damage in the model system. This chapter reviews the different approaches to detecting and quantifying DNA damage using D. melanogaster and the utility of D. melanogaster for assessing genotoxicity.

Cytotoxic effects of silver nanoparticles and non-essential metals in murine macrophages.

Olaparib has synergistic effects with DNA damaging agents in pancreatic ductal adenocarcinoma.