Background:Beryllium and its compounds are carcinogenicity, but the mechanisms through which this occurs have yet to be clarified. Accumulating evidence exists that long noncoding RNAs (lncRNAs) play an important role in occurrence and development of cancer.Aims and Methods:To explore the carcinogenic mechanism of beryllium, human bronchial epithelial cells (16HBE) were treated with 50 μM beryllium sulfate (BeSO4) for 45 passages (~23 weeks). The expression levels of lncRNA SNHG7, SNHG11, SNHG15, MIR22HG, GMPS, and SIK1 were detected at passage 0 (P0), 15 (P15), 25 (P25), 35 (P35), and 45 (P45).Results:The results indicated that enhanced cell proliferation, extensive clones in soft agar, protein expressions of up-regulated matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), proliferating cell nuclear antigen (PCNA), cyclin D1, and down-regulated p53 were all observed at the 45th passage in 16HBE cells. Thus, BeSO4-transformed 16HBE cells (T-16HBE) were established. Meanwhile, the study found that the expression of lncRNA SNHG11 was elevated during malignant transformation. Knockdown of SNHG11 in T-16HBE cells blocked cell proliferation, invasion, and migration, and decreased the protein levels of MMP9, MMP2, PCNA, cyclin D1, but increased p53.Conclusions:The studies revealed that SNHG11 acts as an oncogene in the malignant transformation of 16HBE cells induced by BeSO4, which signifies progress in the study of the carcinogenic mechanism of beryllium.

Context Ellagic acid (EA) is a phenolic constituent in certain fruits and has largely been recognized for its role as an antioxidant compound.Objective To evaluate the effect of EA on beryllium sulphate-induced splenic toxicity in rats.Materials and methods Male Sprague-Dawley rats were divided into four groups. The first group was used as control. Group 2 was exposed to BeSO4 (12 mg/kg, b.w.). Groups 3 and 4 were treated with EA (100 and 300 mg/kg, b.w.) daily for 6 weeks after exposing to BeSO4 (12 mg/kg, b.w.). Various biochemical and molecular biomarkers were assessed in blood and spleen.Results BeSO4-intoxicated rats showed significant higher WBC (6.74 ± 0.20 × 109/L vs. 11.02 ± 1.31 × 109/L, p < 0.05), Neu (1.14 ± 0.11 × 109/L vs. 2.45 ± 0.42 × 109/L, p < 0.05), Lym (3.80 ± 0.83 × 109/L vs. 9.64 ± 1.99 × 109/L, p < 0.05), and PLT (868.4 ± 43.2 × 109/L vs. 1408 ± 77.57 × 109/L, p < 0.05) than normal control animals. Moreover, an increase in MDA with depletion of GSH and SOD activity (all p < 0.05) occurred in the spleen of rats treated with BeSO4. Furthermore, BeSO4-treated rats displayed significantly higher levels of apoptotic markers (Bax, Caspase-3, PARP) (all p < 0.05). EA administration resulted in a significant reversal of hematological and apoptotic markers in beryllium sulphate-intoxicated rats.Discussion and conclusions Our results suggest EA treatment exerts a significant protective effect on BeSO4-induced splenic toxicity in rats.

用生物信息学方法筛选肺腺癌(Lung adenocarcinoma,LUAD)的诊断生物标志物,并分析肺腺癌中免疫细胞浸润情况.从GEO和TCGA数据库下载肺腺癌的表达数据集,利用R软件筛选肺腺癌与正常肺组织间的差异表达基因(DEGs),使用DAVID网站对DEGs进行GO及KEGG富集分析,使用STRING及Cytoscape等工具对DEGs构建蛋白相互作用网络并筛选hub基因;利用Kaplan-Meier法对DEGs进行生存分析,并对hub基因进行ROC分析筛选诊断生物标志物,利用GSEA预测有预后价值的基因参与的信号通路;并用Cibersort软件反卷积算法分析肺腺癌中免疫细胞浸润情况.共得到肺腺癌的234个DEGs,这些基因主要参与信号转导、物质代谢、免疫反应等相关信号通路;构建PPI网络筛选出的20个hub基因中8个存在预后价值(CCNA2、DLGAP5、HMMR、MMP1、MMP9、MMP13、SPP1、TOP2A),ROC分析中DLGAP5、SPP1值分别是0.703、0.706;DLGAP5、SPP1基因表达水平与肺腺癌组织浆细胞、未活化的CD4+记忆细胞、调节T细胞、巨噬细胞M0、M1、M2及中性粒细胞浸润密切相关(P<0.05).肺腺癌中DLGAP5、SPP1具有较高诊断价值且参与肺腺癌组织免疫细胞浸润;DLGAP5、SPP1基因可作为肺腺癌诊断的生物标志物,可为肺腺癌的靶向治疗研究提供新思路.

The N6-methyladenosine (m6A) refers to the methylation of the N6 position of adenosine of RNA adenine. The modification of m6A is one of the most abundant epigenetic modifications in eukaryotic mRNA and non-coding RNA and is controlled by methyltransferases and demethylases. The biological mechanism and significance of m6A have been discovered with the development of m6A sequencing. Various m6A complex components regulate the function of m6A on mRNA. Methyltransferase-like 3 (METTL3) is one of the earliest identified m6A methyltransferases which regulate the functions of m6A. A large number of studies have shown that METTL3 establishes a cross-talk with tumor cells and development of various human diseases. In this review, we will briefly elaborate on the role of METTL3 in biological function, epithelial-mesenchymal transition (EMT), inflammatory response and sensitivity to the resistance of chemo radiotherapies. The underlying molecular mechanism demonstrated by METTL3 may provide a possible target for treating and diagnosing human diseases.

Inhalation of beryllium and its compounds can cause lung injuries, resulting from inflammation and oxidative stress. Multivesicular bodies (MVB), such as exosomes, are membrane vesicles produced by early and late endosomes that mediate intercellular communications. However, the role of exosomes in beryllium toxicity has not been elucidated. This current study aimed to investigate the functional role of exosomes in lung injury resulting from beryllium sulfate (BeSO4). Here, Sprague-Dawley (SD) rats were exposed to 4, 8, and 12 mg/kg BeSO4 by nonexposed intratracheal instillation. Murine macrophage (RAW 264.7) cells were pretreated with 50 nmol/L rapamycin (an mTOR signaling pathway inhibitor) for 30 min and then cultured for 24 h with 100 mu g/mL exosomes, which had been previously isolated from the serum of 12 mg/kg BeSO4-treated SD rats. Compared with those of the controls, exposure to BeSO4 in vivo increased LDH activity, elevated levels of inflammatory cytokines (IL-10, TNF-alpha, and IFN-gamma) alongside inflammation-related proteins expression (COX-2 and iNOS), and enhanced secretion of exosomes from the SD rat's serum. Moreover, the BeSO4-Exos-induced upregulation of LDH activity and inflammatory responses in RAW 264.7 cells can be alleviated following pretreatment with rapamycin. Collectively, these results suggest that serum exosomes play an important role in pulmonary inflammation induced by BeSO4 in RAW 264.7 cells via the mTOR pathway.

Beryllium and its compounds can cause pulmonary interstitial fibrosis through mechanisms that are not yet clear. Long non-coding RNA (lncRNA) is implicated in various diseases. The molecular toxicity of beryllium sulfate (BeSO4) was investigated through the RNA-seq analysis of the lncRNA and mRNA whole-transcriptome of BeSO4-treated 16HBE cells. A total of 1014 lncRNAs (535 upregulated and 479 downregulated) and 4035 mRNAs (2224 upregulated and 1811 downregulated) were found to be significantly dysregulated (|logFC| ≥> 2.0, p < 0.05) in the BeSO4-treated groups when compared with the control group. Five differentially expressed lncRNAs and mRNAs were verified by qRT-PCR. KEGG analysis showed that lncRNA regulates the ECM receiver interaction and PI3K/AKT signaling pathways, etc. In addition, H19:17, lnc-C5orf13-1:1, lnc-CRYAA-17:1, lnc-VSTM5-1:11, and lnc-THSD7A-7:1 may regulate BeSO4-induced 16HBE cytotoxicity through ceRNA mechanism. The results of this study will provide some theoretical support for the study of the toxic mechanism of beryllium and its compounds.

Beryllium and its compounds are systemic toxicants that are widely applied in many industries. Hydrogen sulfide has been found to protect cells. The present study aimed to determine the protective mechanisms involved in hydrogen sulfide treatment of 16HBE cells following beryllium sulfate‐induced injury. 16HBE cells were treated with beryllium sulfate doses ranging between 0 and 300 μM BeSO4. Additionally, 16HBE cells were subjected to pretreatment with either a 300 μM dose of sodium hydrosulfide (a hydrogen sulfide donor) or 10 mM DL‐propargylglycine (a cystathionine‐γ‐lyase inhibitor) for 6 hr before then being treated with 150 μM beryllium sulfate for 48 hr. This study illustrates that beryllium sulfate induces a reduction in cell viability, increases lactate dehydrogenase (LDH) release, and increases cellular apoptosis and autophagy in 16HBE cells. Interestingly, pretreating 16HBE cells with sodium hydrosulfide significantly reduced the beryllium sulfate‐induced apoptosis and autophagy. Moreover, it increased the mitochondrial membrane potential and alleviated the G2/M‐phase cell cycle arrest. However, pretreatment with 10 mM DL‐propargylglycine promoted the opposite effects. PI3K/Akt/mTOR and Nrf2/ARE signaling pathways are also activated following pretreatment with sodium hydrosulfide. These results indicate the protection provided by hydrogen sulfide in 16HBE cells against beryllium sulfate‐induced injury is associated with the inhibition of apoptosis and autophagy through the activation of the PI3K/Akt/mTOR and Nrf2/ARE signaling pathways. Therefore, hydrogen sulfide has the potential to be a promising candidate in the treatment against beryllium disease.

肺癌严重危害人类健康,患者预后较差.肺纤维化是肺癌的危险因素之一,与肺癌的发病机制存在一定关系.肺纤维化中失调的微小RNA(microRNA,miRNA)在肺癌发生发展过程中发挥着重要作用.本研究使用基因表达综合数据库(Gene Expression Omnibus,GEO)中肺纤维化miRNA及肺癌mRNA的芯片数据,利用GEO2R筛选肺纤维化差异miRNA与肺癌差异基因、miRWalk预测miRNA靶基因、STRING分析互作关系、WebGestalt进行GO与KEGG分析、GEPIA分析基因对患者生存的影响,最终获得SNRPE、PIK3R1、ARHGEF6等潜在的肺癌治疗靶点.通过对这些潜在靶点的认识进一步了解肺癌的发生发展机制,为肺癌的临床治疗贡献新的思路.