Long‐term exposure to respirable silica particles causes pulmonary inflammation and fibrosis primarily promoted by cytokines released from alveolar macrophages, yet the underlying mechanism is still unclear. From the perspective of nuclear factor kappa B (NF‐κB), we studied the mechanism of IL‐1β biosynthesis and release. Utilizing BAY 11‐7082, an NF‐κB specific inhibitor, we showed the alteration of macrophage viability and examined the expression of both IL‐1β and NF‐κB in vitro. We found that silica nanoparticles (SiNPs) were internalized by macrophages and caused damage to cell integrity. The immunofluorescence assay showed that SiNPs exposure enhanced the expression of IL‐1β and NF‐κB, which could be effectively suppressed by BAY 11‐7082. Besides, we built silica exposure mouse model by intratracheally instilling 5 mg of SiNPs and checked the effect of silica exposure on pulmonary pathological changes. Consistently, we found an upregulation of IL‐1β and NF‐κB after SiNPs exposure, along with the aggravated inflammatory cell infiltration, thickened alveolar wall, and enhanced expression of collagens. In conclusion, SiNPs exposure causes pulmonary inflammation and fibrosis that is regulated by NK‐κB through upregulating IL‐1β in alveolar macrophages.

Parkinson's disease (PD) is one of the most common neurodegenerative movement disorders, for which there has been no effective treatments. To clarify the pathogenesis of PD, we constructed a competing endogenous RNA (ceRNA) network based on the genome‐wide RNA sequencing data. It was found that 92 RNAs were differentially expressed, including 50 mRNAs, 25 miRNAs and 17 lncRNAs, based on which a ceRNA network was constructed and evaluated from 4 aspects of number of nodes, topological coefficients, closeness centrality and betweenness centrality. The functional annotation and enrichment analysis suggested that 6 functional modules, particularly the peripheral nervous system development and toxin metabolic process, dominated the development of PD. To validate the assumption, the gene set enrichment analysis (GSEA) was conducted basing on the genome‐wide RNAs regardless whether they were differentially expressed or not. Consistently, the results revealed that dysregulation of MAG, HOXB3, MYRF and PLP1 led to metabolic disorders of sphingolipid and glutathione, which contributed to the pathogenesis of PD. Also, in‐depth mining of previous literature confirmed a pivotal role of these dysregulated RNAs, which had been indicated to be potential diagnostic and therapeutic biomarkers of PD. Overall, we constructed a ceRNA network based on the dysregulated mRNAs, lncRNAs and miRNAs in PD, and the aberrant expression of MAG, HOXB3, MYRF and PLP1 caused metabolism disorder of sphingolipid and glutathione, and these genes are of great significance for the diagnosis and treatment of PD.

Exposure to silica nanoparticles (SiNPs) is related to the dysregulation of pulmonary surfactant that maintains lung stability and function. Nevertheless, there are limited studies concerning the interaction and influence between SiNPs and pulmonary surfactant, and the damage and mechanism are still unclear. Herein, we used A549 cells to develop an in vitro model, with which we investigated the effect of SiNPs exposure on the expression of pulmonary surfactant and the potential regulatory mechanism. The results showed that SiNPs were of cytotoxicity in regarding of reduced cell viability and promoted the production of excessive reactive oxygen species (ROS). Additionally, the JNK/c‐Jun signaling pathway was activated, and the expression of surfactant protein A (SP‐A) and surfactant protein B (SP‐B) was decreased. After the cells being treated with N‐acetyl‐L‐cysteine (NAC), we found that the ROS content was effectively downregulated, and the expression of proteins related to JNK and c‐Jun signaling pathways was suppressed. In contrast, the expression of SP‐A and SP‐B was enhanced. Furthermore, we treated the cells with JNK inhibitor and c‐Jun‐siRNA and found that the expression of protein related to JNK and c‐Jun signaling pathways, as well as SP‐A and SP‐B, changed in line with that of NAC treatment. These findings suggest that SiNPs exposure can upregulate ROS and activate the JNK/c‐Jun signaling pathway in A549 cells, thereby inhibiting the expression of SP‐A and SP‐B proteins.

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