Transcriptome analysis of zebrafish embryos exposed to deltamethrin.

Deltamethrin (DTM), a type II pyrethroid, is one of the most commonly used insecticides. The increased use of pyrethroid leads to potential adverse effects, particularly in sensitive populations such as children and pregnant women. None of the related studies was focused on the transcriptome responses in zebrafish embryos after treatment with DTM; therefore, RNA-seq, a high-throughput method, was performed to analyze the global expression of differential expressed genes (DEGs) in zebrafish embryos treated with DTM (40 and 80 µg/L) from fertilization to 48 h postfertilization (hpf) as compared with that in the control group (without DTM treatment). Two cDNA libraries were generated from treated embryos and one cDNA library from nontreated embryos, respectively. Over 92% of reads mapped to the reference in these three libraries. It was observed that many differential genes were expressed in comparison with embryos before and after DTM. The 20 most differentially expressed upregulated or downregulated genes were majorly involved in the signaling transduction. Validation of selected nine genes expression using qRT-PCR confirmed RNA-seq results. The transcriptome sequences were further subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, showing G-protein-coupled receptor signaling pathway and neuroactive ligand-receptor interaction, respectively, were most enriched. The data from this study contributed to a better understanding of the potential consequences of fish exposed to DTM, to an evaluation of the potential threat of DTM to fish populations in aquatic environments. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1548-1557, 2017.

Activation of MAPK pathways and downstream transcription factors in 2-aminobiphenyl-induced apoptosis.

2-Aminobiphenyls (2-ABP) induces oxidative DNA damage and leads to apoptosis. The precise signaling pathways of inducing apoptosis in vitro are still unknown. This study provides insight into the relationship between 2-ABP-induced apoptosis and the activation of MAPK and downstream transcription factors using pharmacological inhibitors of ERK, p38, and JNK pathways. Results showed that 2-ABP induced the activation of ERK and JNK but not p38. The ERK/JNK pathways downstream transcription factors, c-Jun and ATF-2, were also activated by 2-ABP. The inhibitory effects of ERK inhibitor, U0126, on 2-ABP-induced caspase-3 activity were not detected. However, JNK inhibitor, SP600125, significantly attenuated the caspase-3 activity induced by 2-ABP. The expression of the transcription factors c-Jun and ATF-2 were decreased in 2-ABP treated cells in the presence of ERK/JNK inhibitors, suggesting that the expression of ERK/JNK pathways leads to the downstream activation of c-Jun and ATF-2. N-acetylcysteine, an ROS scavenger, inhibited 2-ABP-induced activation of ERK and JNK, the cell death and caspase-3 activity, which suggested that oxidative stress plays a crucial role in apoptosis through activation of caspase-3 in a ROS/JNK-dependent signaling cascade.

Decreasing dosage of irinotecan, 5-flurouracil (5-FU) and leucovorin (LV) in the treatment of advanced and/or metastatic colorectal cancer: a phase II study.

BACKGROUND: In this study, we attempted to determine the efficacy and toxicity of decreasing dosage of irinotecan plus 5-fluorouracil (5-FU) and leucovorin (LV) in the treatment of advanced colorectal cancer. METHODS: A total of 250 mg/m2 Irinotecan (CPT-11) intravenous infusion for 90 minutes was administered every 3 weeks. A 24-hour intravenous infusion with 2000 mg/m2 5-FU and 200 mg/m2 LV was administered through a port-A catheter system weekly for 2 consecutive weeks. Each treatment cycle was repeated every 3 weeks. Progression-free survival and survival curves were drawn according to Kaplan-Meier method. Tumor responses were determined according to the RECIST guidelines. Toxicities were evaluated using the WHO criteria. RESULTS: Thirty-eight patients were enrolled from September 2001 through October 2004. The median number of treatment courses was 8.1 (range, 1-14). Based on the intent-to-treat principle, the response rate was 39.5% (95% CI: 25.4-54.4%) which included 5.3% complete response (CR) and 34.2% partial response (PR). The time to tumor progression was 8.4 months (range, 2-12 months). The median time of survival was 18.4 months (range, 4-26 months). The major toxicities were grade 1 neutropenia and grade 2 diarrhea. Toxic death was not found in this study. The efficacy of this regimen was compatible with the reports of the clinical trials in the United States and European countries but fewer incidence of toxicity was found in our results. CONCLUSION: The results revealed that our combination regimen of 5-FU/LV + CPT-11 is a highly effective and acceptable protocol. This treatment is easily performed in an outpatient clinic. The biggest advantage is that all patients were intensively cared by the physicians to maintain a quality of life, and only 26.3% of patients showed progressive disease. Therefore, this regimen may be considered to be used in the treatment of patients with terminal cancer. A further randomized study comparing this regimen with oral fluoropyrimidines plus irinotecan is warranted.