資訊中心 > 產品文獻集 > Safety Assessment (22)

  ✔本篇論文使用華聯產品:Human OneArray  
 Toxicology Research. 2015, 4, 365-375. doi: 10.1039/C4TX00181H.
 A gene signature for gold nanoparticle-exposed human cell lines 
 Ruei-yue Liang, Hsin-fang Tu, Xiaotong Tan, Yu-shan Yeh, Pin Ju Chueh, Show-mei Chuang
  Abstract
There is currently a significant need for effective methods aimed at diagnosing and screening for nanoparticle exposure. We previously investigated the toxicity of three different particle sized gold nanoparticles (AuNPs) toward different types of mammalian cells and explored a related gene expression profile by cDNA microarray analysis of AuNP-exposed MRC-5 cells. In this study, we sought to further identify genes that could be used as biomarkers for AuNP exposure. We used cDNA microarray analysis to obtain comprehensive gene expression profiles from A549 cells exposed to three different-sized AuNPs. A total of 409 genes were commonly up-regulated by the tested AuNPs; of them, 71 had previously been analyzed to be up-regulated in MRC-5 cells. Among the top-ranked 30 of these 71 up-regulated genes, based on the magnitude of induction, nine genes were confirmed to be transcriptionally induced in A549 cells by all three tested AuNPs, as assessed by quantitative real-time polymerase chain reaction (qPCR). Among them, TSC22D3, TRIB3, PCK2 and DDIT4 were the most sensitive to the three AuNPs, and showed dose-dependent changes in several human cell lines. qPCR and immunoblotting analyses revealed that the same concentrations of micro-Au and nano-TiO2 failed to elicit up-regulation of these four genes at the mRNA and protein levels in any tested cell lines. Although the definition and practical implementation of specific biomarkers for nanoparticles is still in its infancy, our data suggest that it may be possible to define reliable biomarkers for the diagnosis of nanomaterial exposure.
   

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  ✔本篇論文使用華聯產品:Mouse OneArray  
 Molecular Medicine Reports. 2015, 11(2):887-95. doi: 10.3892/mmr.2014.2823.
 Biological effect of ketamine in urothelial cell lines and global gene expression analysis in the bladders of ketamine‑injected mice
 
 
 Cheng‑huang Shen, Shou‑tsung Wang, Ying‑ray Lee, Shiau‑yuan Liu, Yi‑zhen Li, Jiann‑der Wu, Yi‑ju Chen, Yi‑wen Liu
  Abstract
Ketamine is used clinically for anesthesia but is also abused as a recreational drug. Previously, it has been established that ketamine‑induced bladder interstitial cystitis is a common syndrome in ketamine‑abusing individuals. As the mechanisms underlying ketamine‑induced cystitis have yet to be revealed, the present study investigated the effect of ketamine on human urothelial cell lines and utilized a ketamine‑injected mouse model to identify ketamine‑induced changes in gene expression in mice bladders. In the in vitro bladder cell line assay, ketamine induced cytotoxicity in a dose‑ and time‑dependent manner. Ketamine arrested the cells in G1 phase and increased the sub‑G1 population, and also increased the barrier permeability of these cell lines. In the ketamine‑injected mouse model, ketamine did not change the body weight and bladder histology of the animals at the dose of 30 mg/kg/day for 60 days. Global gene expression analysis of the animals' bladders following data screening identified ten upregulated genes and 36 downregulated genes induced by ketamine. A total of 52% of keratin family genes were downregulated, particularly keratin 6a, 13 and 14, which was confirmed by polymerase chain reaction analysis. Keratin 14 protein, one of the 36 ketamine‑induced downregulated genes, was also reduced in the ketamine‑treated mouse bladder, as determined by immunohistochemical analysis. This suggested that cytotoxicity and keratin gene downregulation may have a critical role in ketamine‑induced cystitis.
   

  ✔本篇論文使用華聯產品:Mouse&Rat miRNA OneArray  
 Environmental Toxicology. 2015, 30(6):712-23. doi: 10.1002/tox.21949.
 Prenatal and neonatal exposure to perfluorooctane sulfonic acid results in aberrant changes in miRNA expression profile and levels in developing rat livers
 
 
 Fan Wang, Yihe Jin, Faqi Wang, Junsheng Ma, Wei Liu
  Abstract
Perfluorooctane sulfonate (PFOS) is an animal carcinogen. However, the underlying mechanism in cancer initiation is still largely unknown. Recently identified microRNAs (miRNAs) may play an important role in toxicant exposure and in the process of toxicant-induced tumorigenesis. We used PFOS to investigate PFOS-induced changes in miRNA expression in developing rat liver and the potential mechanism of PFOS-induced toxic action. Dams received 3.2 mg/kg PFOS in their feed from gestational day 1 (GD1) to postnatal day 7 (PND 7). Pups then had free access to treated feed until PND 7. We isolated RNAs from liver tissues on PND 1 and 7 and analyzed the expression profiles of 387 known rat miRNAs using microarray technology. PFOS exposure induced significant changes in miRNA expression profiles. Forty-six miRNAs had significant expression alterations on PND 1, nine miRNAs on PND 7. Specifically, expression of four miRNAs was up-regulated on PND 7 but down-regulated on PND1 (p < 0.05). Many aberrantly expressed miRNAs were related to various cancers. We found oncogenic and tumor-suppressing miRNAs, which included miR-19b, miR-21*, miR-17-3p, miR-125a-3p, miR-16, miR-26a, miR-1, miR-200c, and miR-451. In addition, four miRNAs were simultaneous significantly expressed on both PND 1 and 7. Functional Annotation analysis of the predicted transcript targets revealed that PFOS exposure potentially alters pathways associated with different cancers (cancer, melanoma, pancreatic cancer, colorectal cancer, and glioma), biological processes which include positive regulation of apoptosis and cell proliferation. Results showed PFOS exposure altered the expression of a suite of miRNAs.
   

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  ✔本篇論文使用華聯產品:Human OneArray  
 Bmc Cancer. DOI 10.1186/s12885-015-1671-5.
 Upregulation of MicroRNA-19b predicts good prognosis in patients with hepatocellular carcinoma presenting with vascular invasion or multifocal disease
 
 
 
  Abstract
Background After surgical resection of hepatocellular carcinoma (HCC), recurrence is common, especially in patients presenting with vascular invasion or multifocal disease after curative surgery. Consequently, we examined the expression pattern and prognostic value of miR-19b in samples from these patients. Methods We performed a miRNA microarray to detect differential expression of microRNAs (miRNAs) in 5 paired samples of HCC and non-tumoral adjacent liver tissue and a quantitative real-time polymerase chain reaction (PCR) analysis to validate the results in 81 paired samples of HCC and adjacent non-tumoral liver tissues. We examined the associations of miR-19b expression with clinicopathological parameters and survival. MiR-19b was knocked down in Hep3B and an mRNA microarray was performed to detect the affected genes. Results In both the miRNA microarray and real-time PCR, miR-19b was significantly overexpressed in the HCC tumor compared with adjacent non-tumor liver tissues (P < 0.001). The expression of miR-19b was significantly higher in patients who were disease-free 2 years after surgery (P < 0.001). High miR-19b expression levels were associated with higher α-fetoprotein levels (P = 0.017). In the log-rank test, high miR-19b was associated with better disease-free survival (median survival 37.107 vs. 11.357; P = 0.022). In Cox multivariate analysis, high miR-19b predicted better disease-free survival and overall survival (hazards ratio [HR] = 0.453, 95 % confidence interval [CI] = 0.245–0.845, P = 0.013; HR = 0.318, CI = 0.120–0.846, P = 0.022, respectively). N-myc downstream regulated 1 (NDRG1) was downregulated, while epithelial cell adhesion molecule (EPCAM), hypoxia-inducible factor 1-alpha (HIF1A), high-mobility group protein B2 (HMGB2), and mitogen activated protein kinase 14 (MAPK14) were upregulated when miR-19b was knocked down in Hep3B. Conclusions The overexpression of miR-19b was significantly correlated with better disease-free and overall survival in patients with HCC presenting with vascular invasion or multifocal disease after curative surgery. MiR-19b may influence the expression of NDRG1, EPCAM, HMGB2, HIF1A, and MAPK14.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 Amino Acids. doi: 10.1007/s00726-015-1956-7. Epub 2015 Mar 24..
 Homocysteine thiolactone and N-homocysteinylated protein induce pro-atherogenic changes in gene expression in human vascular endothelial cells
 
 
 
  Abstract
Genetic or nutritional deficiencies in homocysteine (Hcy) metabolism lead to hyperhomocysteinemia (HHcy) and cause endothelial dysfunction, a hallmark of atherosclerosis. In addition to Hcy, related metabolites accumulate in HHcy but their role in endothelial dysfunction is unknown. Here, we examine how Hcy-thiolactone, N-Hcy-protein, and Hcy affect gene expression and molecular pathways in human umbilical vein endothelial cells. We used microarray technology, real-time quantitative polymerase chain reaction, and bioinformatic analysis with PANTHER, DAVID, and Ingenuity Pathway Analysis (IPA) resources. We identified 47, 113, and 30 mRNAs regulated by N-Hcy-protein, Hcy-thiolactone, and Hcy, respectively, and found that each metabolite induced a unique pattern of gene expression. Top molecular pathways affected by Hcy-thiolactone were chromatin organization, one-carbon metabolism, and lipid-related processes [−log(P value) = 20–31]. Top pathways affected by N-Hcy-protein and Hcy were blood coagulation, sulfur amino acid metabolism, and lipid metabolism [−log(P value)] = 4–11; also affected by Hcy-thiolactone, [−log(P value) = 8–14]. Top disease related to Hcy-thiolactone, N-Hcy-protein, and Hcy was ‘atherosclerosis, coronary heart disease’ [−log(P value) = 9–16]. Top-scored biological networks affected by Hcy-thiolactone (score = 34–40) were cardiovascular disease and function; those affected by N-Hcy-protein (score = 24–35) were ‘small molecule biochemistry, neurological disease,’ and ‘cardiovascular system development and function’; and those affected by Hcy (score = 25–37) were ‘amino acid metabolism, lipid metabolism,’ ‘cellular movement, and cardiovascular and nervous system development and function.’ These results indicate that each Hcy metabolite uniquely modulates gene expression in pathways important for vascular homeostasis and identify new genes and pathways that are linked to HHcy-induced endothelial dysfunction and vascular disease.