Tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardants (BFRs). It has been detected in various environment media and has been approved to be high toxic to aquatic organisms. However, the exposure levels of TBBPA in the main watersheds in China have not been investigated sufficiently. In this study TBBPA concentrations in water, sediment and tissues of four fish species from Lake Chaohu were determined. Spatial and temporal distribution patterns of TBBPA in water and sediment, and the relationship among TBBPA concentrations in fish tissues and fish size were analyzed. The results showed that the maximum TBBPA concentration in sediment was 518 ng/g in March 2008. It is almost the highest value than those ever reported anywhere in the world. In lake water, TBBPA level reached the maximum value of 4.87 μg/L in July. Tissue distributions of TBBPA in four fish species were similar, and the mean concentrations in the fish were in the range of 28.5-39.4 ng/g, much higher than those reported in Japan, Europe, and the United States. The maximum concentrations of TBBPA were found in kidneys where TBBPA concentration was positively correlated with fish size of Cyprinus carpio. Results demonstrated a widespread distribution of TBBPA in Lake Chaohu. The source was mainly inflow rivers near the cities. The distribution coefficient among water, fish, and sediment was 1:28:117. This indicated that sediment was the main repository for TBBPA within Lake Chaohu. Furthermore, TBBPA may pose a potential ecological risk in the lake during summer.

No abstract

Lung cancer is the leading cause of cancer death worldwide. Recently, two plant-derived drugs triptolide (TP) and hydroxycamptothecin (HCPT) both have shown broad-spectrum anticancer activities. Our previous study documented that combination treatment with these two drugs acted more effectively than mono-therapy, however, the molecular basis underlying the synergistic cytotoxicity remains poorly understood. In this study, we aimed to clarify the molecular mechanism of TP/HCPT anticancer effect in A549 lung adenocarcinoma cells, by investigating the involvement of phosphatase 2A (PP2A) and PP2A-regulated mitogen-activated protein kinases (MAPKs) and Akt signaling pathways. The results showed that TP and HCPT synergistically exerted cytotoxicity in the growth of A549 cells. Combinatorial TP/HCPT treatment significantly enhanced the activation of caspase-3 and -9, Bax/Bcl-2 ratio, release of cytochrome c from mitochondrial and subsequent apoptosis. While the Akt survival pathway was inhibited, ERK and p38 MAPKs were dramatically activated. Furthermore, the activity of PP2A was significantly augmented. Regulation of p38, ERK and Akt by PP2A was demonstrated, by using a specific PP2A inhibitor okadaic acid (OA). Finally, pharmacological inhibitors OA, SB203580, SP600125 and PD98059 confirm the role of PP2A and its substrates ERK, p38 MAPK and Akt in mediating TP/HCPT-induced apoptosis. Taken together, this study provides the first evidence for a synergistic TP/HCPT anti-cancer activity in A549 cells and also supports a critical role of PP2A and PP2A-regulated signaling pathways, providing new insight into the mode of action of TP/HCPT in cancer therapy.

Abstract:Objective: To understand the function of nicotinamide N-methyltransferase (NNMT) protein as tumor biomarker in renal carcinoma. Methods: Recombinant NNMT protein was used to prepare monoclonal antibodies by hybridoma technique. The diagnostic and prognostic function of NNMT protein in renal carcinoma was evaluated by analyzing 74 renal cancer tissues through immunohistochemical staining for NNMT by using the prepared antibodies. Results: Two hybridomas named 2F8 and 1E7 stably secreting the monoclonal antibodies were isolated successfully, and characters such as isotypes and specificity were determined. NNMT protein was significantly up-regulated in renal cancer and significantly associated with tumor histology and ages. The univariate survival analysis demonstrated that the pT-status, high levels of NNMT, and distant metastasis were significant prognosticators. Conclusion: NNMT is over-expressed in a large proportion in renal cell cancers. High NNMT expression is significantly associated with unfavorable prognosis. However, the prognostic value of NNMT needs further verification in larger sample sizes.

No abstract

No abstract

Background/Aims: Triptolide (TP) is a diterpenoid triepoxide extracted from the traditional Chinese medical herb Tripterygium wilfordii that exerts prominent broad-spectrum anticancer activity to repress proliferation and induce cancer cell apoptosis through various molecular pathways. We previously observed that TP inhibits the progression of A549 cells and pancreatic cancer cells (PNCA-1) in vitro. However, the complex molecular mechanism underlying the anticancer activity of TP is not well understood. Methods: To explore the molecular mechanisms by which TP induces lung cancer cell apoptosis, we investigated changes in the protein profile of A549 cells treated with TP using a proteomics approach (iTRAQ [isobaric tags for relative and absolute quantitation] combined with NanoLC-MS/MS [nano liquid chromatographymass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools OmicsBean and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and were verified using western blotting. Apoptosis and cell cycle effects were analyzed using flow cytometry. Results: TP induced apoptosis in A549 cells and blocked A549 cells at the G2/M phase. Using iTRAQ technology, we observed 312 differentially expressed proteins associated in networks and implicated in different KEGG pathways. Gene Ontology (GO) analysis showed the overviews of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Moreover, some candidate proteins involved in PARP1/AIF and nuclear Akt signaling pathways or metastasis processes were validated by western blotting. Conclusion: TP exerted anti-tumor activity on non-small cell lung cancer (NSCLC) A549 lung adenocarcinoma cells by dysregulating tumor-related protein expression. Herein, we provide a preliminary study of TP-related cytotoxicity on A549 cells using proteomics tools. These findings may improve the current understanding of the anti-tumor effects of TP on lung cancer cells and may reveal candidate proteins as potential targets for the treatment of lung cancer.

YhdE, a Maf-like protein in Escherichia coli, exhibits nucleotide pyrophosphatase (PPase) activity, yet its cellular function remains unknown. Here, we characterized the PPase activity of YhdE on dTTP, UTP and TTP and determined two crystal structures of YhdE, revealing ‘closed’ and ‘open’ conformations of an adaptive active site. Our functional studies demonstrated that YhdE retards cell growth by prolonging the lag and log phases, particularly under stress conditions. Morphology studies showed that yhdE-knockout cells transformed the normal rod shape of wild-type cells to a more spherical form, and the cell wall appeared to become more flexible. In contrast, YhdE overexpression resulted in filamentous cells. This study reveals the previously unknown involvement of YhdE in cell growth inhibition under stress conditions, cell-division arrest and cell-shape maintenance, highlighting YhdE’s important role in E. coli cell-cycle checkpoints.