Colorectal cancer tumor stem cells mediate bevacizumab resistance through the signal IL-22-STAT3 signaling pathway.

Bevacizumab is the standard treatment for colorectal cancer (CRC) in the advanced stage. However, poor diagnosis identified due to the bevacizumab resistance in many CRC patients. Previous studies have found that CRC stem cells (CCSCs) and interleukin 22 (IL-22) are involved in the resistance of bevacizumab, however, the mechanism of remains unclear. In this study, we established the bevacizumab drug-resistant cell line HCT-116-R by concentration gradient method, and the cell viability was detected by CCK-8 assay. The resistance of bevacizumab in CRC cell lines HCT-116-R was identified by characterizing epithelial-mesenchymal transition (EMT). Additionally, HCT-116-R cell lines were isolated from CCSCs and their tumorigenicity was validated in nude mice. We observed that that compared with the matched group, the expression of IL-22, IL-22R, STAT3, and GP130 in drug-resistant cells increased distinctly, with blocked IL-22 cells were successfully constructed by lentiviral interference. The level of proteins in stem cell landmarks (EpCAM, CD133), and stem cell landmarks (Oct4, Sox2) was identified by western blotting. Furthermore, the IL-22 role was evaluated by xenograft model. We found that short hairpin RNA (shRNA) suppression of IL-22 expression can restore the sensitivity of drug-resistant CCSCs to bevacizumab, Moreover, xenograft tumor models show that suppression of IL-22 can increase the anti-tumor influence of bevacizumab. In summary, we demonstrated that CCSCs play a major part in bevacizumab-resistant CRC. Inhibiting the signaling pathway of IL-22/STAT3 can improve the anti-tumor influence on bevacizumab in vitro and in vivo. Thus, IL-22 may represent a new anti-bevacizumab target in CRC.

A hydrophilic naphthalimide-based fluorescence chemosensor forCu2+ ion: Sensing properties, cell imaging and molecular logic behavior.

In this work, a hydrophilic naphthalimide-based fluorescence chemosensor (sensor 1) was synthesized for Cu2+ recognition, in which 2-(2-aminoethoxy)ethanol was introduced to improve the hydrophily and Schiff base acted as the multidentate ligand for Cu2+. The effect factors, sensing mechanism and regenerability of sensor 1 for Cu2+ sensing were systematically investigated. It was found that sensor 1 displayed a long emission wavelength of 532 nm upon excited in visible light region (436 nm), and the good water solubility made it utilized in aqueous media. It could selectively react with Cu2+ over other common metal ions to form a 2:1 complex within 1 min and result in significant fluorescence quench. The fluorescence change was linear to 0.5-10.0 µmol L-1 of Cu2+ with a low detection limit of 3.74 × 10-8 mol L-1. Sensor 1 has been successfully utilized for analyzing Cu2+ in water samples as well as imaging cellular Cu2+. Moreover, in view of fluorescence "on-off-on" switches of sensor 1 induced by Cu2+ and EDTA, an IMPLICATION logic gate was constructed based on fluorescence mode with Cu2+ and EDTA as inputs.

Monolithic column functionalized with quinine derivative for anion-exchange capillary electrochromatography.

A novel anion-exchange organic polymer monolithic column based on monomers N-benzylquininium chloride and acrylamide were firstly prepared by in situ copolymerization for capillary electrochromatography. Moreover, N-benzylquininium was firstly introduced as a strong anion-exchange functional group. A relatively strong anodic EOF was obtained in the pH values from 4.0 to 9.0, which was in the same direction with the electrophoretic mobility of acid compounds. Hence, the anion-exchange monolithic column was very suitable for the rapid separation of acid compounds. Eight acid compounds (2-chlorobenzoic acid, mandelic acid, 4-hydroxybenzoic acid, indole-3-acetic acid, 2-aminoterephthalic acid, 3,5-pyridinedicarboxylic acid, benzoic acid, and 4-aminobenzoic acid) were successfully separated on the monolithic column. The highest column efficiency was 4.60 × 105 plates/m (theoretical plates, N) for 3,5-pyridinedicarboxylic acid. The proposed monolithic column was characterized by SEM and FT-IR. The RSDs of the acid compounds migration time for run-to-run, day-to-day, and column-to-column were all less than 5.0%.