Influence of soil properties on cadmium accumulation in vegetables: Thresholds, prediction and pathway models based on big data.

Soil properties, such as soil pH, soil organic matter (SOM), cation exchange capacity (CEC), are the most important factors affecting cadmium (Cd) accumulation in vegetables. In this study, we conducted big data mining of 31,342 soil and vegetable samples to examine the influence of soil properties (soil pH, SOM, CEC, Zn and Mn content) on the accumulation of Cd in root, solanaceous, and leafy vegetables in Hunan Province, China. Specifically, the Cd accumulation capability was in the following order: leafy vegetables > root vegetables > solanaceous vegetables. The soil property thresholds for safety production in vegetables were determined by establishing nonlinear models between Cd bioaccumulation factor (BCF) and the individual soil property, and were 6.5 (pH), 30.0 g/kg (SOM), 13.0 cmol/kg (CEC), 100-140 mg/kg (Zn), and 300-400 mg/kg (Mn). When soil property values were higher than the thresholds, Cd accumulation in vegetables tended to be stable. Prediction models showed that pH and soil Zn were the leading factors influencing Cd accumulation in root vegetables, explaining 87% of the variance; pH, SOM, soil Zn and Mn explained 68% of the variance in solanaceous vegetables; pH and SOM were the main contributors in leafy vegetables, explaining 65% of the variance. Further, variance partitioning analysis (VPA) revealed that the interaction effect of the corresponding key soil properties contributed mostly to BCF. Meanwhile, partial least squares (PLS) path modeling was employed to analyze the path and the interactive effects of soil properties on Cd BCF. pH and SOM were found to be the biggest two players affecting BCF in PLS-models, and the most substantial interactive influence paths of soil properties on BCF were different among the three types of vegetables.

Input and output of cadmium (Cd) for paddy soil in central south China: fluxes, mass balance, and model predictions.

It is important to provide a more comprehensive understanding of cadmium (Cd) input and output in different contamination zones. In this study, we choose 15 sampling areas in three types of contamination zones (industrial and mining, suburb, and rural) to systematically study the inventory of soil Cd input and output in Changzhutan (CZT) urban agglomerations, Hunan Province, China. The results showed that the value of total Cd input in industrial and mining (34.58 g/ha/year) was respectively about 2 and 3 times of that in suburb and in rural. Meanwhile, the total output flux in industrial and mining also presented highest value (38.67 g/ha/year) among the zones. As for the contributions, atmospheric deposition was responsible for 85-89% of the total input fluxes, which was significantly higher than those of irrigation water and fertilizer. Crop harvesting, especially straw removal, was the dominant output pathway, contributing 66-78%. Moreover, Cd annual balance illustrated that the net input fluxes under straw removal scenario were negative in all zones, and it was opposite under straw returning scenario. Further, the changes of soil Cd concentrations under straw returning and straw removal scenario were compared by a dynamic mathematical model. The modeling results presented that the soil Cd content continued to increase under straw returning in 100 years, while it was declining under straw removal scenario. This prediction indicated straw removal was an important remediation for Cd-polluted paddy soil, especially in Hunan. Nevertheless, more treatment measures need to conduct to reach the safety limits in paddy soil.

miR200c attenuates P-gp-mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer.

MicroRNA-200c (miR200c) recently emerged as an important regulator of tumorigenicity and cancer metastasis; however, its role in regulating multidrug resistance (MDR) remains unknown. In the current study, we found that the expression levels of miR200c in recurrent and metastatic colorectal cancers were significantly lower, whereas the JNK2 expression was higher compared with primary tumors. We showed that in MDR colorectal cancer cells, miR200c targeted the 3' untranslated region of the JNK2 gene. Overexpression of miR200c attenuated the levels of p-JNK, p-c-Jun, P-gp, and MMP-2/-9, the downstream factors of the JNK signaling pathway, resulting in increased sensitivity to chemotherapeutic drugs, which was accompanied by heightened apoptosis and decreased cell invasion and migration. Moreover, in an orthotopic MDR colorectal cancer mouse model, we demonstrated that overexpression of miR200c effectively inhibited the tumor growth and metastasis. At last, in the tumor samples from patients with locally advanced colorectal cancer with routine postsurgical chemotherapy, we observed an inverse correlation between the levels of mRNA expression of miR200c and JNK2, ABCB1, and MMP-9, thus predicting patient therapeutic outcomes. In summary, we found that miR200c negatively regulated the expression of JNK2 gene and increased the sensitivity of MDR colorectal cancer cells to chemotherapeutic drugs, via inhibiting the JNK2/p-JNK/p-c-Jun/ABCB1 signaling. Restoration of miR200c expression in MDR colorectal cancer may serve as a promising therapeutic approach in MDR-induced metastasis.

Zuo Jin Wan reverses P-gp-mediated drug-resistance by inhibiting activation of the PI3K/Akt/NF-κB pathway.

BACKGROUND: Zuo-Jin-Wan (ZJW), a traditional Chinese medicine formula, has been identified to be effective against drug resistance in cancer. In the present study, we investigated the effect of ZJW on acquired oxaliplatin-resistant and the PI3K/Akt/NF-κB pathway in vitro. METHODS: We tested the dose-response relationship of ZJW on reversing drug-resistance by CCK-8 assay and flow cytometry analysis in vitro. The protein expression of P-gp, MRP-2, LRP, and ABCB1 mRNA expression level were evaluated by Western blot and quantitative RT-PCR. The activities of PI3K/Akt/NF-κB pathway were also examined with or without ZJW, including Akt, IκB, p65 and their phosphorylation expression. RESULTS: We found that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs and increased oxaliplatin (L-OHP)-induced cell apoptosis in a time- and dose-dependent manner. Moreover, both ZJW and a PI3K specific inhibitor (LY294002) suppressed phosphorylation of Akt (Ser473) and NF-κB, which is necessary in the activation of the PI3K/Akt/NF-κB pathway. The effect of ZJW in reversing drug-resistance and suppressing phosphorylation of Akt (Ser473) and NF-κB were weakened after treatment with a PI3K/Akt activator in HCT116/L-OHP cells. CONCLUSIONS: Our study has provided the first direct evidence that ZJW reverses drug-resistance in human colorectal cancer by blocking the PI3K/Akt/NF-κB signaling pathway, and could be considered as a useful drug for cancer therapy.

Zuo Jin Wan, a Traditional Chinese Herbal Formula, Reverses P-gp-Mediated MDR In Vitro and In Vivo.

Zuo Jin Wan (ZJW), a typical traditional Chinese medicine (TCM) formula, has been identified to have anticancer activity in recent studies. In this study, we determined the underlying mechanism of ZJW in the reversal effect of multidrug resistance on colorectal cancer in vitro and in vivo. Our results showed that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs in HCT116/L-OHP, SGC7901/DDP, and Bel/Fu MDR cells. Moreover, combination of chemotherapy with ZJW could reverse the drug resistance of HCT116/L-OHP cells, increase the sensitivity of HCT116/L-OHP cells to L-OHP, DDP, 5-Fu, and MMC in vitro, and inhibit the tumor growth in the colorectal MDR cancer xenograft model. ICP-MS results showed that ZJW could increase the concentration of chemotherapeutic drugs in HCT116/L-OHP cells in a dose-dependent manner. Furthermore, we showed that ZJW could reverse drug resistance of colorectal cancer cells by decreasing P-gp level in vitro and in vivo, which has been represented as one of the major mechanisms that contribute to the MDR phenotype. Our study has provided the first direct evidence that ZJW plays an important role in reversing multidrug resistance of human colorectal cancer and may be considered as a useful target for cancer therapy.