Separation and identification of degradation impurities of esomeprazole sodium.

Drug impurities are important factors that affect drug safety and efficacy. The aim of this study is to separate and confirm the structure of two degradation impurities of esomeprazole sodium, designated X and Y. The impurities X and Y were successfully isolated using preparative HPLC by developing separation methods with the help of ACD/Labs AutoChrom software. There was a steady increase in X and Y impurities in forced esomeprazole sodium degradation. Impurity X was confirmed as 6-methoxy-1h-benzo[d]imidazole-2-yl-4-amino-3,5-dimethylpyridinecarboxylate and impurity Y as 6-methoxy-1h-benzo[d]imidazole-2-yl-4-hydroxy-3,5-dimethylpyridinecarboxylate using nuclear magnetic resonance spectrometry, infrared spectroscopy, and high-resolution mass spectrometry. These findings provide a comprehensive understanding of the impurity profile of esomeprazole sodium because these impurities are reported for the first time. Based on our results, active pharmaceutical ingredient manufacturers can further control process parameters to reduce impurity generation, and drug production manufacturers can optimize the packaging and storage conditions of esomeprazole sodium.

Knockdown of metadherin inhibits cell proliferation and migration in colorectal cancer.

Metadherin (MTDH) is a multifunctional oncogene involved in tumor cell migration and metastasis through regulating a number of oncogenic signaling pathways in various human malignancies. Previous studies have demonstrated that MTDH is overexpressed in human colorectal cancer (CRC) and associated with cancer progression and a poor prognosis. However, the underlying mechanisms remain largely unknown. The present study investigated the expression and role of MTDH in CRC cells as well as the underlying mechanism of this. Western blot analysis and quantitative polymerase chain reaction were conducted to determine protein and mRNA expression of MTDH in three human CRC cell lines. A short hairpin RNA (shRNA) targeting MTDH was introduced into CRC HCT116 cells to stably inhibit MTDH expression. A Cell Counting Kit­8 assay, colony formation assay, Transwell assay and flow cytometry were used to investigate the effect of MTDH­knockdown on cell proliferation, migration, apoptosis and cell cycle arrest. Western blotting was performed to examine the protein expression levels of cell growth­ and apoptosis­associated genes. The results demonstrated that MTDH was commonly expressed in CRC cell lines. MTDH silencing significantly suppressed cell growth, colony forming ability and migration while inducing the apoptosis of HCT116 cells. In addition, MTDH depletion induced S phase cell cycle arrest in HCT116 cells. Mechanistically, knockdown of MTDH markedly downregulated the expression of phosphorylated protein kinase B, c­Myc, proliferating cell nuclear antigen and B­cell lymphoma 2 (Bcl­2) protein in HCT116 cells, and the expression of p53 and Bcl­2­associated X protein was significantly increased compared with the negative control shRNA group (P<0.05), suggesting that MTDH may function through the expression of numerous types of apoptosis­associated and signaling channel proteins in CRC cells. Taken together, these data indicated that MTDH may serve as a biomarker and candidate therapeutic target for CRC.

Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in hepatocellular carcinoma cells.

This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival. Six2 expression was higher in clinical HCC tissues than in normal tissues, and was negatively correlated with E-cadherin expression. Additionally, six2 overexpression decreased the sensitivity of HCC cells to 5-Fu, characterized as attenuating 5-FU-induced cell apoptosis and downregulation of cell viability, and promoted HCC cells stemness. Mechanistically, six2 overexpression repressed E-cadherin expression via stimulating promoter methylation of the E-cadherin. And E-cadherin overexpression rescued six2-induced decrease of 5-FU sensitivity and promotion on HCC cells stemness. Therefore, our results suggest that Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in HCC cells.

Polycyclic aromatic hydrocarbons in water, sediment, soil, and plants of the Aojiang River waterway in Wenzhou, China.

The town of Shuitou was renowned as the leather capital of China because of its large-scale tanning industry, but the industry's lack of pollution controls has caused severe damage to the local water system. This study determined 15 priority polycyclic aromatic hydrocarbons (PAHs) in water, sediment, soil, and plant samples collected from Aojiang River and its estuary. The total PAHs ranged from 910 to 1520 ng/L in water samples. The total PAH in sediments were moderate to low in comparison with other rivers and estuaries in China, but the relative proportions of PAHs per million people are high when considering the population size associated with each watershed. Ratios of fluoranthene/pyrene and PAHs with low/high molecular weight suggest a petrogenic PAH origin. The PAH composition profile in soil was similar to that in sediment with 4-6 ring PAHs being dominant. The PAHs with 2-3 rings were the dominant species in plant leaves. There were no correlations between PAHs in soils and in plants, suggesting that PAHs accumulate in plant leaves through absorption from the air. The general observation of elevated PAH concentrations in all matrix suggests a possible contribution by the local leather industry on the PAH concentrations in the Aojiang watershed.

Solid-phase extraction combined with dispersive liquid-liquid microextraction for the determination for polybrominated diphenyl ethers in different environmental matrices.

An analytical method, solid-phase extraction combined with dispersive liquid-liquid microextration (SPE-DLLME), was established to determine polybrominated diphenyl ethers (PBDEs) in water and plant samples. After concentration and purification of the samples in LC-C18 column, 1.0-mL elution sample containing 22.0 microL 1,1,2,2-tetrachloroethane was injected rapidly into the 5.0-mL pure water. After extraction and centrifuging, the sedimented phase was injected rapidly into gas chromatography with electron-capture detection (GC-ECD). For water samples, enrichment factors (EFs) are in the range of 6838-9405 under the optimum conditions. The calibration curves are linear in the range of 0.1-100 ng L(-1) (BDEs 28, 47) and 0.5-500 ng L(-1) (BDEs 100, 99, 85, 154, 153). The relative standard deviations (RSDs) and the limits of detection (LODs) are in the range of 4.2-7.9% (n=5) and 0.03-0.15 ng L(-1), respectively. For plant samples, RSDs and LODs are in the range of 5.9-11.3% and 0.04-0.16 microg kg(-1), respectively. The relative recoveries of well, river, sea, leachate, and clover samples, spiked with different levels of PBDEs, are 66.8-94.1%, 72.2-100.5%, 74.5-110.4%, 62.1-105.1%, 66.1-91.7%, 62.4-88.9%, and 64.5-83.2%, respectively. The results show that SPE-DLLME is a suitable method for the determination of PBDEs in water and plant samples.