RESUMO
Fine particulate matter (PM2.5) is a risk factor for pulmonary diseases and lung cancer, and inhaled PM2.5 is mainly deposited in the bronchial epithelium. In this study, we investigated the effect of long-term exposure to low-dose PM2.5 on BEAS-2B cells derived from the normal bronchial epithelium. BEAS-2B cells chronically exposed to a concentration of 5⯵g/ml PM2.5 for 30 passages displayed the phenotype promoting epithelial-mesenchymal transition (EMT) and cell invasion. Cellular internalization of exosomes (designated PM2.5 Exo) extracted from BEAS-2B cells chronically exposed to low-dose PM2.5 promoted cell invasion in vitro and metastatic potential in vivo. Hence, to identify the key players driving phenotypic alterations, we analyzed microRNA (miRNA) expression profiles in PM2.5 Exo. Five miRNAs with altered expression were selected: miRNA-196b-5p, miR-135a-2-5p, miR-3117-3p, miR-218-5p, and miR-497-5p. miR-196b-5p was the most upregulated in both BEAS-2B cells and isolated exosomes after PM2.5 exposure. In a functional validation study, genetically modified exosomes overexpressing a miR-196b-5p mimic induced an enhanced invasive phenotype in BEAS-2B cells. Conversely, miR-196b-5p inhibition diminished the PM2.5-enhanced EMT and cell invasion. These findings indicate that exosomal miR-196b-5p may be a candidate biomarker for predicting the malignant behavior of the bronchial epithelium and a therapeutic target for inhibiting PM2.5-triggered pathogenesis.
Assuntos
Brônquios , Células Epiteliais , Transição Epitelial-Mesenquimal , Exossomos , Neoplasias Pulmonares , MicroRNAs , Material Particulado , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Exossomos/metabolismo , Exossomos/genética , Exossomos/efeitos dos fármacos , Material Particulado/toxicidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/patologia , Brônquios/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Invasividade Neoplásica , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Linhagem Celular TumoralRESUMO
This research endeavors to elevate indoor air quality within aging school environments by concentrating on refining interior finishing materials and windows. Renovations, encompassing window and floor remodeling in classrooms, aim to mitigate particulate matter (PM) infiltration and enhance air exchange rates. Utilizing SPS30 sensors for the analysis of 0.3-2.5 µm particles, with a focus on their implications for human health, the study evaluated air exchange rates, deposition rates, infiltration rates, and particle generation during classroom activities. Post-renovation results demonstrated a noteworthy decrease in air exchange rates, indicating an enhancement in airtightness. The investigation delves into particle generation with various flooring materials, accentuating the importance of opting for durable and low-particle-generating alternatives. Health risk assessments, considering multiple exposure routes (inhalation, dermal contact, and ingestion), revealed reduced risks post-renovation, particularly for children. To further optimize indoor air quality, the study suggests the implementation of air purification systems. Examination of PM generation during student activities showcased a substantial reduction post-renovation. This study underscores the positive influence of architectural enhancements on indoor air quality while acknowledging the necessity for holistic solutions and continuous research.
Assuntos
Poluição do Ar em Ambientes Fechados , Material Particulado , Instituições Acadêmicas , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Poluição do Ar em Ambientes Fechados/análise , Material Particulado/análise , Humanos , Pisos e Cobertura de Pisos , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análiseRESUMO
The lysine 4 of histone H3 (H3K4) can be methylated or acetylated into four states: H3K4me1, H3K4me2, H3K4me3, or H3K4ac. Unlike H3K4 methylation, the genome-wide distribution and functional roles of H3K4ac remain unclear. To understand the relationship of acetylation with methylation at H3K4 and to explore the roles of H3K4ac in the context of chromatin, we analyzed H3K4ac across the human genome and compared it with H3K4 methylation in K562 cells. H3K4ac was positively correlated with H3K4me1/2/3 in reciprocal analysis. A decrease in H3K4ac through the mutation of the histone acetyltransferase p300 reduced H3K4me1 and H3K4me3 at the H3K4ac peaks. H3K4ac was also impaired by H3K4me depletion in the histone methyltransferase MLL3/4-mutated cells. H3K4ac peaks were enriched at enhancers in addition to the transcription start sites (TSSs) of genes. H3K4ac of TSSs and enhancers was positively correlated with mRNA and eRNA transcription. A decrease in H3K4ac reduced H3K4me3 and H3K4me1 in TSSs and enhancers, respectively, and inhibited the eviction of histone H3 from them. The mRNA transcription of highly transcribed genes was affected by the reduced H3K4ac. Interestingly, H3K4ac played a redundant role with regard to H3K27ac in eRNA transcription. These results indicate that H3K4ac serves as a marker of both active TSSs and enhancers and plays a role in histone eviction and RNA transcription by leading to H3K4me1/3.
Assuntos
Elementos Facilitadores Genéticos , Histonas , Sítio de Iniciação de Transcrição , Transcrição Gênica , Histonas/metabolismo , Humanos , Células K562 , Acetilação , Metilação , Cromatina/metabolismo , RNA/metabolismo , RNA/genéticaRESUMO
Siloxanes, widely used in various consumer and industrial products, are emerging concerns of contaminants. Despite this, limited studies have been conducted on contamination and time trends on siloxanes in coastal environments. In the present study, four cyclic and 15 linear siloxanes were measured in sediments collected from an artificial saltwater lake in Korea during 2001-2016 to investigate contamination, time trends, and ecotoxicological concerns. Cyclic siloxanes were detected in all sediment samples, whereas linear siloxanes were not frequently detected. The highest siloxane concentrations were observed in creeks passing through various industrial complexes, indicating that industrial activities predominantly contributed to siloxane contamination in coastal environments. Decamethylcyclopentasiloxane (D5) and dodecylcyclohexasiloxane (D6) were predominant siloxanes in sediments over the last two decades. Siloxane concentrations significantly increased in creek sediments from 2008 to 2016, whereas those in inshore and offshore regions significantly decreased due to a strong dilution effect by the operation of tidal power plant. This suggests that consumption patterns and coastal development activities are crucial factors determining the contamination and time trends in the sedimentary siloxanes. The sedimentary concentrations of octamethylcyclotetrasiloxane (D4) and D5 exceeded several thresholds, raising the potentials for ecological risks to aquatic organisms.