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• On day 28, lung fibrosis in silica-induced rats was confirmed. • Silica induces changes in 682 lncRNAs (300 upregulated, 382 downregulated). • The predicted target mRNAs of lncRNAs of silicosis involves in 13 pathways. • "Proteoglycans in cancer" signaling pathway in pulmonary fibrosis is valuable to study. • LncRNA-miRNA-mRNA ceRNA network may play an important role in pulmonary fibrosis. Silicosis is a kind of chronic and incurable lung fibrotic disease with pathogenesis and molecular mechanisms largely unknown. Mounting evidence suggests that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of silicosis. However, how many lncRNAs involved in the pulmonary fibrosis remains to be elucidated. In this study, Wistar rats were exposed to silicon dioxide by an improved tracheal intubation method. Rats in the control group were treated with normal saline solution. Results showed that 28 days after exposure, there were significant differences in body weight and lung coefficient of rats treated with silica compared with control rats. The formation of lung fibrosis in silica-induced rats was confirmed by histologic examination. We then investigated the lncRNAs expression changes in lung tissues of silica-exposed rats and compared that with the rats in the control group using microarray. The results indicated that silica exposure leads to altered expression profile in 682 lncRNAs (300 upregulated and 382 downregulated). Seventy-three ceRNA pairs were acquired by predicted analysis. Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses were used to predict the biological pathway and functional classification of lncRNAs. The results showed that silica exposure affected 13 lncRNAs pathways. The functional classification mainly involved in protein binding, cell shape and extracellular exosome. This study indicated that alteration of lncRNAs may play a role in silica-induced pulmonary fibrosis through regulation of expressions of functional genes in lungs of rat. Our results provide more insights into the mechanism of silicosis. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Silica induced EMT and pulmonary fibrosis in rats. • TGF-β1/Smad2/3 was involved at 14 days and 28 days after silica instillation. • Pirfenidone inhibited EMT and silicosis fibrosis in rats. • The effects of PFD on silicosis rats may be related to TGF-β1/Smad2/3 pathway. Abstract To study the role of pirfenidone in rats exposed to silica dust, we established the rat silicosis model with 50 mg/ml silica by intratracheal instillation. From the first day after silica instillation, rats were given pirfenidone (50, 100 mg/kg/day) and rats were sacrificed at 14 days and 28 days to observe the histopathology of lungs, to analyze the level of TNF-α, IL-1β, IL-6 in lung tissues and to measure the expression of TGF-β1, Smad2/3, vimentin, and E-cadherin in lung tissues. Results showed that pirfenidone (50, 100 mg/kg/day) reduced the silica-induced alveolar inflammation, the damage of alveolar structure and the blue areas of collagen fibers in the lungs of rats. At the same time, pirfenidone also reduced the level of TNF-α, IL-1β, IL-6 in lung tissues and the protein expression of collagen I. After pirfenidone intervention for 14 days and 28 days, the protein expression of vimentin was down-regulated and the protein expression of E-cadherin was up-regulated in lung tissues. In addition, the TGF-β1/smad2/3 pathway was activated at 14 days and 28 days after silica instillation, and pirfenidone reduced the expression of TGF-β1 and smad2/3 in the lungs. These results indicated that pirfenidone intervention inhibited the epithelial-mesenchymal transition and pulmonary fibrosis in rat silicosis model, which effects may be related to the TGF-β1/smad pathway. [ABSTRACT FROM AUTHOR]

Atrazine (AZ) is an environmental endocrine disrupting chemical which can affect the development of amphibians. In our past studies, we demonstrated that chronical exposure to 100 μg/L AZ can cause abnormalities in development and related genes expression of gonads in developing male Xenopus laevis ( X. laevis ) tadpoles. Recent studies by others have demonstrated that circular RNAs (circRNAs) are implicated in multiple developmental anomalies. However, whether circRNAs involve in the effects in AZ-exposed X. laevis remains unknown. In this study, over 68575 circRNAs were detected by circRNA sequencing of testis tissues from control groups ( n  = 3) and AZ-treated X. laevis ( n  = 3). Treatment of AZ led to 405 circRNAs differentially expressed including 44 upregulated and 361 downregulated compared with froglets in the control groups. Two upregulated and 6 downregulated circRNAs were further validated by real-time PCR assay which displayed consistent regulation patterns as shown by the transcriptome sequencing results. Two hundreds and eighty two differentially expressed circRNAs played miRNA sponges roles. Kyoto Encyclopedia of Genes and Genomes pathway analysis of miRNA targets showed that AZ-affected circRNAs are mainly involved in 19 pathways. The Wnt signaling pathway and progesterone-mediated oocyte maturation pathway may be two involved signal pathways. This study for the first time provides evidence that AZ can alter circRNAs which play a role in AZ-induced testicular degeneration of developing male X. laevis through regulation of expressions of functional genes in the testes of X. laevis. [ABSTRACT FROM AUTHOR]

As a widely used herbicide, atrazine (AZ) has been extensively studied for its adverse effects on the reproductive system, especially feminization in male animals. However, the relationship of gene expression changes and associated toxicological endpoints remains unclear. In this study, developing Xenopus laevis tadpoles were exposed to concentration of AZ at 0.1, 1, 10 or 100 μg/L continuously. Compared with froglets in the control group, there were no significant differences in body length, body weight, liver weight and hepatosomatic index (HSI) of males in groups treated with AZ for 90 d. At 100 μg/L AZ treatment caused a significant reduction of gonad weight and gonadosomatic index (GSI) of males ( p < 0.01). In addition, AZ at all dose levels caused testicular degeneration, especially in froglets from the groups with 0.1 and 100 μg/L which exhibited U-shaped dose-response trend. We further investigated the gene expression changes associated with the testicular degeneration induced by AZ. We found that the expression of 1165 genes was significantly altered with 616 upregulated and 549 downregulated compared to the expression profile of the control animals. KEGG analysis showed that genes which were significantly affected by AZ are mainly involved in arginine and proline metabolism, cell cycle, riboflavin metabolism, spliceosome, base excision repair and progesterone-mediated oocyte maturation pathway. Our results show that AZ may affect reproductive and immune systems by interference with the related gene expression changes during the male X. laevis development. The findings may help to clarify the feminization mechanisms of AZ in male X. laevis . [ABSTRACT FROM AUTHOR]

Although it has been well recognized that benzene exposure can cause hematopoietic disorders such as aplastic anemia and leukemia, the underlying molecular mechanism remains to be fully understood. Emerging evidence indicated that aryl hydrocarbon receptor (AhR) plays important roles in hematopoietic and immune systems. This study investigated the activation of aryl hydrocarbon receptor (AhR) by hydroquinone (HQ) and its role in HQ-induced DNA damage and apoptosis in cultured human lymphocytes (JHP cells). We also investigated the effect of ROS on AhR activation and functions in JHP cells exposed to HQ with and without regulator including N-acetyl- l -cysteine (NAC), a potent antioxidant, and tert-butylhydroquinone (TBHQ), a Nrf2 activator. Results showed that HQ can cause oxidative stress, DNA damage and apoptosis. Pretreatment of an AhR antagonist (CH223191) can significantly increase the cell survival and mitigate HQ-induced toxicities such as DNA damage and apoptosis. We found that HQ can obviously increase expressions of total protein of AhR and prompt nuclear translocation compared to the control group. Interestingly, NAC can block HQ-induced AhR activation and DNA damage and apoptosis. Conclusively, our results indicated that HQ toxicity is mediated by AhR which is in turn regulated by ROS generated by HQ. The interaction between AhR and ROS drive and amplify the hematopoietic toxicity of HQ. This study provided new insights of mechanism and potential targets for the prevention and treatment to benzene-induced hematopoietic toxicity. [Display omitted] • Hydroquinone (HQ) induced nuclear translocation of AhR. • Inhibition of both AhR and ROS attenuated HQ-induced DNA damage and apoptosis. • AhR inhibition attenuated HQ-induced ROS production. • ROS inhibition attenuated HQ-induced AhR activity. [ABSTRACT FROM AUTHOR]

To explore the potential role of HMGB1 on TDI-induced NLRP3 inflammasome activation, HBE cells were treated with TDI-HSA conjugate to observe the changes of HMGB1, TLR4, NF-κB, Nrf2 and NLRP3 inflammasome related proteins expressions, ROS release and MMP. NAC, TPCA-1 and Resatorvid pre-treatments were applied to explore the effects of ROS, NF-κB and TLR4 on TDI-induced NLRP3 inflammasome activation. The CRISPR/Cas9 system was used to construct HMGB1 gene knockout HBE cell line and then to explore the role of HMGB1 on TDI-HSA induced NLRP3 inflammasome activation. GL pre-treatment was applied to further confirm the role of HMGB1. Results showed that TDI increased HMGB1, TLR4, P-p65, Nrf2 proteins expressions and ROS release, decreased MMP level and activated NLRP3 inflammasome in HBE cells in a dose dependent manner. NAC, TPCA-1 and Resatorvid pre-treatments decreased the expression of P-p65 and inhibited NLRP3 inflammasome activation. Inhibition of HMGB1 decreased Nrf2 expression and ROS release, improved MMP level and reduced NLRP3 inflammasome activation. GL ameliorated NLRP3 inflammasome activation via inhibiting HMGB1 regulated ROS/NF-κB pathway. These results indicated that HMGB1 was involved in TDI-induced NLRP3 inflammasome activation as a positive regulatory mechanism. The study provided a potential target for early prevention and treatment of TDI-OA. [ABSTRACT FROM AUTHOR]

Toluene-diisocyanate (TDI) is one of the main causes of occupational asthma. To study the role of autophagy in TDI-induced airway inflammation and airway remodeling in bronchial airway epithelial (16HBE) cells. We treated 16HBE cells with TDI-human serum albumin (TDI-HSA) conjugate to observe reactive oxygen species (ROS) release, autophagy activation, airway inflammation and airway remodeling. 3-Methyladenine (3-MA) and Rapamycin (Rapa) intervention were used to explore the effects of autophagy on inflammatory response and protein expression related to airway remodeling in 16HBE cells treated with TDI-HSA. Experimental results suggested that various concentrations of TDI-HSA (0, 40, 80 and 120 μg/mL) increased the release of ROS and the expression of Nrf2, activated autophagy and increased the expression of AMPK, Beclin-1, LC3 and decreased the expression of p62, promoted the levels of IL-5, IL-6 and IL-8 in 16HBE cells. Results also showed that E-cadherin expression decreased but an increase was observed in α-SMA and MMP-9 in the TDI-HSA group. The treatment of TDI-HSA combined with Rapa aggravated the above reaction whereas the inverse was true for TDI-HSA combined with 3-MA. These results indicated that autophagy is involved in TDI-induced airway inflammation and airway remodeling as a positive regulatory mechanism, inhibiting autophagy can significantly alleviate the TDI-induced inflammatory response and attenuate airway remodeling protein expression in 16HBE cells. • TDI-HSA increased the release of ROS, activated the expression of LC3β and Beclin-1 and decrease the expression of P62. • TDI-HSA increased IL-5, IL-6 and IL-8 levels, α-SMA and MMP-9 expression and decreased E-cadherin expression in 16HBE cells. • TDI-HSA + Rapa aggravated the airway inflammation and remodeling whereas the inverse was true for TDI-HSA + 3-MA. • Autophagy is involved in TDI-induced airway inflammation and remodeling as a positive regulatory mechanism in 16HBE cells. [ABSTRACT FROM AUTHOR]

Recent discovery of reversible N6-methyladenosine (m6A) methylation on messenger RNA (mRNA) and mapping of m6A methylomes in mammals, plant and yeast revealed potential regulatory functions of this RNA modification. However, the role of the m6A methylomes in amphibious is still poorly understood. Here, we examined the m6A transcriptome-wide profile in testis tissues of Xenopus laevis (X. laevis) with and without treatment with 100 μg/L atrazine (AZ) through m6A sequencing analysis using the latest Illumina HiSeq sequencer. The results revealed that m6A is a highly conserved modification of mRNA in X. laevis. Distinct from that in mammals, m6A in X. laevis is enriched around the stop codon and start codon, as is reported in plant. We then investigated the differential expression m6A in testes of AZ-exposed X. laevis and compared that with the X. laevis in the control group by m6A sequencing. The results indicated that AZ leads to altered expression profile in 1380 m6A modification sites (696 upregulated and 684 downregulated). KEGG pathway analysis indicates that the "NOD-like receptors", "tight junction", "Peroxisome proliferator-activated receptors", "adherens junctions", "Glycerophospholipid metabolism" and "Fatty acid biosynthesis" signaling pathways may be associated with abnormal testis development of X. laevis due to exposure to AZ. Analysis results showed a positive correlation between m6A modification and mRNA abundance, suggesting a regulatory role of m6A in amphibious gene expression. Our first report of m6A transcriptome-wide map of an amphibian species X. laevis presented here provides a starting roadmap for uncovering m6A functions that may affect/control amphibian testis development. • m6A is a highly conserved modification of mRNA in amphibians compared to human. • m6A in X. laevis is enriched around the stop and start codon, as is found in plant. • A positive correlation between m6A modification and mRNA abundance. • AZ leads to altered expression profile in 1380 m6A modification sites. • Six signaling pathways may be related to abnormal testis development of X. laevis. [ABSTRACT FROM AUTHOR]