Capecitabine inhibits epithelial-to-mesenchymal transition and proliferation of colorectal cancer cells by mediating the RANK/RANKL pathway.

Colorectal cancer (CRC) is the third most prevalent malignancy globally. Capecitabine is an important form of chemotherapy for colorectal cancer. The present study aims to investigate the underlying mechanism of action of the drug in CRC cells. In the present study, 50 pairs of CRC and adjacent normal tissues were collected, and CRC cell lines (SW480, SW620, HT29, LOVO and HCT116) and NCM460 colonic epithelial cells were also purchased and used. Western blotting was used to measure the expression levels of proteins involved in the receptor activator of nuclear factor-κB (RANK)/receptor activator of nuclear factor-κB ligand (RANKL) pathway and epithelial-to-mesenchymal transition (EMT), including RANK, RANKL, osteoprotegerin (OPG), E-cadherin, vimentin and N-cadherin. Proliferation and migration were measured using MTT, Cell Counting Kit-8, EdU, Transwell and wound healing assays, respectively. In the present study, it was found that the RANK/RANKL pathway was activated in cancer tissues and cells. Additionally, it was observed that capecitabine treatment reduced the protein expression of RANK, RANKL and OPG in HT29 cells, suggesting that capecitabine has a repressive effect on the RANK/RANKL pathway. Furthermore, functional experiments revealed that the proliferative ability and the EMT process observed in HT29 cells were inhibited after they were treated with capecitabine or transfected with si-RANK. Rescue assays were then performed, which revealed that the promotion of RANK via transfection of cells with 50 nM pcDNA3.1-RANK reversed the inhibitory effects of capecitabine on HT29 cell proliferation and EMT. These findings suggest that the regulatory role of capecitabine is at least partially mediated through the RANK/RANKL pathway in colorectal cancer. The present study demonstrated that capecitabine-induced repression of CRC is exerted by inhibiting the RANK/RANKL pathway, where this new mechanism potentially provides a novel therapeutic target.

A nitrile-mediated aptasensor for optical anti-interference detection of acetamiprid in apple juice by surface-enhanced Raman scattering.

Currently, the detection of pesticide is critical for food safety assurance, but it is still challenging due to the presence of biological interferents from complex food matrix. In this study, we developed an optical anti-interference surface-enhanced Raman scattering (SERS) aptasensor system for trace detection of acetamiprid. 4-(Mercaptomethyl) benzonitrile (MMBN) containing CN bond was used as Raman tag to provide a sharp peak (2227 cm-1) in the Raman-silent spectral window (1800-2800 cm-1) where no Raman signal existed for most of molecules. Gold nanoparticles (AuNPs) bonded with polyadenine (polyA)-mediated aptamer and Raman tag (MMBN-AuNPs-aptamer) was synthesized as Raman probe, while the complementary DNA (cDNA) conjugated with AgNPs-decorated silicon wafer (AgNPs@Si) was used as SERS substrate. As acetamiprid molecule could specifically combine with aptamer, preventing the formation of MMBN-AuNPs-aptamer-cDNA-AgNPs@Si (expressed as "Au-AgNPs@Si") hybrid through DNA sequence linking, Raman signal intensities of MMBN in Au-AgNPs@Si decreased when the concentration of acetamiprid increased. Under the optimum assay condition, the proposed method displayed a linear response for acetamiprid detection in the range of 25-250 nM with a low detection limit of 6.8 nM. Finally, the developed aptasensor was successfully used to determine acetamiprid content in apple juice. Accordingly, this novel anti-interference SERS aptasensor could be a promising acetamiprid sensor for food safety assurance.

Excluding PTV from lung volume may better predict radiation pneumonitis for intensity modulated radiation therapy in lung cancer patients.

BACKGROUND: Lung dose-volume histogram (DVH) in radiotherapy could be calculated from multiple normal lung definitions. The lung dosimetric parameters generated from various approaches are significantly different. However, limited evidence shows which definition should be used to more accurately predict radiation pneumonitis (RP). We aimed to compare the RP prediction accuracy of dosimetric parameters from three lung volume methods in lung cancer patients treated with Intensity-Modulated Radiation Therapy (IMRT). METHODS: We retrospectively reviewed 183 consecutive lung cancer patients treated with IMRT from January 2014 to October 2017. The normal lungs were defined by total bilateral lung volume (Total Lung), excluding PTV (Lung-PTV) or PGTV (Lung-PGTV). V5, V20, and mean lung dose (MLD) have been extracted from three definitions. The primary endpoint was acute grade 2 or higher RP (RP2). Correlation between RP2 and dose parameters were analyzed by logistic regression. We evaluated prediction performance using area under the receiver operating characteristic curve (AUC) and normal tissue complication probability (NTCP) model. RESULTS: Twenty-six patients (14.2%) developed acute RP2 after IMRT treatment. Significant dosimetric differences were found between any 2-paired lung volumes (Ps < 0.001). To limit RP2 incidence less than 20%, the cutoff MLDs were 12.5 Gy, 14.2 Gy, and 15.0 Gy, respectively, for Lung-PTV, Lung-PGTV, and Total Lung methods. There were 54% (13% vs. 20%) and 45% (20% vs. 29%) RP2 probability variances detected at each MLD cutoff points from Lung-PTV and Lung-PGTV definitions. The best RP prediction performance was found in MLD from Lung-PTV method (AUC = 0.647), which is significantly better (P = 0.006) than the MLD from Lung-PGTV method (AUC = 0.609). CONCLUSION: There are significant differences in acute RP2 rate prediction using dosimetric parameters from various normal lung definitions. Excluding PTV from total lung volume may be more accurate and promising to predict acute symptomatic radiation pneumonitis in IMRT treated lung cancer patients.

Preparation of an intelligent pH film based on biodegradable polymers and roselle anthocyanins for monitoring pork freshness.

This study aims to develop an intelligent indicating film based on biodegradable polymers incorporated with roselle anthocyanins to monitor pork freshness. Three different films were prepared by using two substances of starch, polyvinyl alcohol and chitosan. The UV-vis spectra and color of anthocyanins changed at pH 2-12. SEM photographs showed that the compatibility of films was improved with the addition of anthocyanins. Furthermore, the polyvinyl alcohol/chitosan/roselle anthocyanins film had the highest tensile strength (98.28 MPa). The starch/polyvinyl alcohol/roselle anthocyanins film had the highest antioxidant activity (524.07%) and the best color stability. The starch/polyvinyl alcohol/roselle anthocyanins film showed visible changes from red to green when employed to monitor the freshness of pork stored at 25 °C, before the TVB-N value of the pork gradually increased to the rejection limit (15 mg/100 g) at 36 h. Therefore, the indicator film can be used to monitor pork freshness for intelligent packaging.

OCT4 Potentiates Radio-Resistance and Migration Activity of Rectal Cancer Cells by Improving Epithelial-Mesenchymal Transition in a ZEB1 Dependent Manner.

Radiotherapy is an important strategy for rectal cancer patient treatment. However, the efficiency of radiation is usually poor, especially in patients with advanced stage rectal cancer due to the radio-resistance developed. At the present study, OCT4 was found to play a critical role in radio-resistance development in human rectal cancer cells by improving the epithelial-mesenchymal transition process (EMT). Endogenous OCT4 expression could confer resistant phonotype on human rectal cancer cells, which was supported by the data from clonogenic forming assay and cell cycle arrest recovering experiment. EMT related transcription factor ZEB1 might take part in the radio-resistance induced by OCT4, as its expression could be upregulated by OCT4 and its silence could reverse the OCT4 induced resistance to radiation in SW480 cells. More interestingly, CHK1 was also upregulated in OCT4/ZEB1 dependent manner conferring stronger DNA damage repair activity on cancer cells, which might explain the underlying mechanisms why OCT4/ZEB1 axis could promote the resistance of human rectal cancer cell to radiation. Taken together, our results provided a novel mechanism for radio-resistance development in human rectal cancer cells and a new target to overcome this resistance.