Knockdown of ABCB7 inhibits esophageal cancer progression by inhibiting the TGF-ß/Smad signaling.

OBJECTIVES: Esophageal cancer accounts for the seventh in human cancers, and the sixth in the global cancer death. ATP-binding cassette, sub-family B (MDR/TAP), member 7 (ABCB7) maintains intracellular iron homeostasis and involved in the regulation of tumor progression. However, the role and mechanism of ABCB7 in esophageal cancer remained unclear. METHODS: Here, we investigated its role and regulatory mechanism by knocking down ABCB7 in Eca109 and KYSE30 cells. RESULTS: ABCB7 was significantly upregulated in esophageal cancer tissues, and was strongly associated with metastasis and poor prognosis of patients. ABCB7 knockdown inhibits the proliferation, migration and invasion of esophageal cancer cells. Importantly, ABCB7 knockdown induces apoptosis and non-apoptotic cell death in flow cytometry analysis. Higher intracellular total iron concentration was observed in ABCB7 knockdown Eca109 and KYSE30 cells. We further analyzed ABCB7 expression related genes in esophageal cancer tissues. COX7B were positively correlated with the expression of ABCB7 in 440 esophageal cancer tissues. COX7B rescued the inhibition of cell proliferation and elevated total iron concentration induced by ABCB7 knockdown. In addition, Western blot results showed that ABCB7 knockdown reversed the epithelial-mesenchymal transition (EMT) process and inhibited the TGF-ß signaling pathway in Eca109 and KYSE30 cells. CONCLUSION: In conclusion, ABCB7 knockdown inhibits the TGF-ß signaling pathway, inhibits the survival of esophageal cancer cells by inducing cell death, and reverses the EMT process. Targeting ABCB7 or COX7B could be a novel strategy for the treatment of esophageal cancer.

Occurrence, Distribution, and Human Exposure of Several Endocrine-Disrupting Chemicals in Indoor Dust: A Nationwide Study.

Parabens, triclosan (TCS), triclocarban (TCC), and bisphenol A and its analogues (BPs) are used in various industrial and consumer products and are typical endocrine-disrupting chemicals (EDCs). In this study, six parabens, TCS, TCC, and eight BPs were determined in 289 indoor dusts collected from different geographical regions in China. Ten of 16 target compounds were found in >50% samples. Concentrations of Σ6parabens, Σ(TCS+TCC), and Σ8BPs in indoor dust ranged from 8.66-21,500 (median: 288), 19.6-8940 (104), and 8.80-37,400 (377) ng/g dw, respectively. The Σ(TCS+TCC) concentrations in dust from Northeast China were higher than those from Central South China (p < 0.05). The concentrations of Σ8BPs in dust from Eastern China were approximately 2 times higher than those found for North China (p < 0.05), whereas there was no significant spatial difference in concentrations of parabens among different geographical regions (p > 0.05). Human exposure to these EDCs through indoor dust ingestion and dermal absorption was evaluated. The median and 95th percentile estimated daily intakes of Σ16EDCs ranged from 0.439 (adults)-4.57 (infants) and 6.26 (adults)-62.1 (infants) ng/kg bw/day, respectively, generally decreasing with increasing age. This nationwide survey establishes a baseline concentration for parabens in the indoor environment in China.

Occurrence of and human exposure to benzothiazoles and benzotriazoles in mollusks in the Bohai Sea, China.

The Bohai Sea is a semi-enclosed sea in northern China with highly industrialized and urbanized coastal areas and concomitant environmental degradation. Benzothiazoles (BTHs) and benzotriazoles (BTRs) are produced in high volume and widely applied in industrial and consumer products, and little is known about their occurrence and bioaccumulation in coastal marine invertebrates. We determined the concentrations of six BTH and five BTR analogues in mollusks (n = 166) collected from the Bohai Sea between 2006-2014. The total concentrations of BTHs were 229-13800 ng/g dry weight (dw) with a geometric mean of 778 ng/g dw and 7.19-322 ng/g dw for BTRs with a geometric mean of 54.6 ng/g dw. Benzothiazole (BTH) was the dominant compound among the BTHs, accounting for 83.0 % of the total concentration. Among the BTRs, 5,6-dimethyl-1-H-benzotriazole (XTR), 5-methyl-1-H-benzotriazole (5-Me-1-H-BTR), and benzotriazole (1-H-BTR) were major contributors, cumulatively accounting for 78.5 % of the total concentration. Mollusks accumulated elevated levels of BTHs/BTRs regardless of species, suggesting a considerable bioaccumulation potential of BTHs/BTRs in marine ecosystems. Human daily dietary intake of BTHs/BTRs through the consumption of mollusks was estimated based on the concentrations measured. This is the first report on the occurrence and distribution patterns of BTHs/BTRs in a variety of marine invertebrate species from a coastal ecosystem.

Spatial distribution of parabens, triclocarban, triclosan, bisphenols, and tetrabromobisphenol A and its alternatives in municipal sewage sludges in China.

Parabens, triclocarban (TCC), triclosan (TCS), bisphenols (BPs), and tetrabromobisphenol A and its alternatives (TBBPAs) are used in a broad range of daily consumer products and industrial productions. Concerns have been raised over exposure of humans to these chemicals, because of their adverse health effects. However, information on the spatial distribution of parabens, TCC, TCS, BPs and TBBPAs in sludge from waste water treatment plants (WWTPs) in China is still limited. In this study, 19 endocrine disrupting chemicals, including six parabens, two antimicrobials (TCC and TCS), eight BPs and three TBBPAs, were determined in sludges from 46 WWTPs across China. Concentrations of target chemicals were found in a decreased order as: ∑(TCC+TCS) (mean: 3930, range: 1340-11,100ng/g dw)>∑8BPs (201, 23.1-1240ng/g dw)>∑6parabens (67.9, 10.4-272ng/g dw)>∑3TBBPAs (18.4, 1.36-195ng/g dw). Methyl paraben (MeP), TCC, bisphenol A (BPA) and tetrabromobisphenol A (TBBPA) were the major compounds found in sludge, accounting for 89.0%, 57.7%, 85.8% and 93.3% of ∑6parabens, ∑(TCC+TCS), ∑8BPs and ∑3TBBPAs, respectively. Elevated concentrations of BPs and TBBPAs were found in sludges from the Northeast China and Central South China (p<0.05), respectively, whereas there were no significant spatial difference in concentrations of parabens or antimicrobials among different geographical regions (p>0.05). Calculation of mass loading showed that sludge from East China (1340kg/yr) and South Central China (1060kg/yr) released relatively more such chemicals. This nationwide study provided baseline concentrations of these chemicals in sludges and estimated their environmental release through sludge in China.

Spatial distribution and mass loading of phthalate esters in wastewater treatment plants in China: An assessment of human exposure.

The occurrence and fate of nine phthalate esters (PAEs), including dimethyl phthalate (DMP), diethyl phthalate (DEP), di­n­butyl phthalate (DBP), di-isobutyl phthalate (DIBP), benzyl butyl phthalate (BzBP), di (2­ethylhexyl) phthalate (DEHP), di­n­hexyl phthalate (DNHP), dicyclohexyl phthalate (DCHP), and di­n­octyl phthalate (DNOP), in sludges collected from 46 wastewater treatment plants (WWTPs) from 22 Chinese provinces were investigated. The nine PAEs were detected in almost all the sludge samples. DEHP was the most abundant congener in all sludge samples, followed by DBP and DIBP. The DEHP concentrations in sludge were in the range of 0.326-67.8 (mean: 14.7) µg/g dry weight (dw), which were at the lower bound or middle of the concentration range of DEHP in sludge globally (0.0200-3514 µg/g dw). Spatial distribution and mass loading of PAEs in WWTPs were investigated. The concentrations of Σ9PAEs in sludges from different provinces were in the order as follows: Jilin (40.2 µg/g dw) > Liaoning (38.9 µg/g dw) > Beijing (30.7 µg/g dw), while the mass loading of ∑9PAEs in sludges were Guangdong (10.1 tons/yr) > Liaoning (9.97 tons/yr) > Shandong (5.59 tons/yr). Our study showed that the geographical distribution of PAEs in sludges was similar to that in indoor dusts found in earlier study, suggesting the existence of a common source for these chemicals in both matrices. Based on the concentrations measured, human exposure to PAEs through sludge application in soil was evaluated and the exposure dose is minor.

Phthalate esters in indoor dust from several regions, China and their implications for human exposure.

Phthalate esters (PAEs) have been used in large quantities all over the world for decades, leading to ubiquitous occurrence in the indoor environment. Indoor dust samples were collected from six geographical regions in China (n = 120) and the concentrations, profiles and human exposure to nine prevalent PAEs from dust were investigated in this study. The total concentrations of nine PAEs (Σ9PAEs) varied from 2.31 to 1590 µg/g (mean: 150 µg/g). The highest concentration of Σ9PAEs was found for dusts from the geographical region of Northeast China (mean: 394 µg/g), which was nearly 8 times higher than that of the lowest value for dusts from the Southwest China (52.1 µg/g). The sum concentrations of six priority controlled PAEs, namely dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BzBP), bis (2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), in our study (mean: 133 µg/g) were lower than those found in other regions of the world (230-1280 µg/g) reported in earlier studies. DEHP, DBP and di-iso-butyl phthalate (DIBP) were the major congeners found in all dust samples, cumulatively accounting for 98.7% of Σ9PAEs. The daily intake (DI) of PAEs via dust through the routes of ingestion, inhalation and dermal contact was estimated. Comparably, dust ingestion is the major pathway of human exposure to PAEs from dust and the DI values through dust ingestion were 985 ng/kg/day for children and 126 ng/kg/day for adults in China, respectively. The contribution of indoor dust to the total exposure of human to PAEs varied, depending on the type of PAE congeners. Among PAE congeners, DEHP was the predominant contributor, accounting for 3.45% and 2.39% of the estimated total DIs for Chinese children and adults, respectively. This indicates that indoor dust is an important source of human exposure to certain PAE congeners.