Chemotherapy resistance observed in patients with colorectal cancer (CRC) may be related to the presence of cancer stem cells (CSCs), but the underlying mechanism(s) remain unclear. Carcinoma-associated fibroblasts (CAFs) are intimately involved in tumor recurrence, and targeting them increases chemo-sensitivity. We investigated whether fibroblasts might increase CSCs thus mediating chemotherapy resistance. CSCs were isolated from either patient-derived xenografts or CRC cell lines based on expression of CD133. First, CSCs were found to be inherently resistant to cell death induced by chemotherapy. In addition, fibroblast-derived conditioned medium (CM) promoted percentage, clonogenicity and tumor growth of CSCs (i.e., CD133+ and TOP-GFP+) upon treatment with 5-fluorouracil (5-Fu) or oxaliplatin (OXA). Further investigations exhibited that exosomes, isolated from CM, similarly took the above effects. Inhibition of exosome secretion decreased the percentage, clonogenicity and tumor growth of CSCs. Altogether, our findings suggest that, besides targeting CSCs, new therapeutic strategies blocking CAFs secretion even before chemotherapy shall be developed to gain better clinical benefits in advanced CRCs.

Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.

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Pyridine-functionalized mesoporous silica was prepared via direct condensation of tetraethoxysilane (TEOS) and N-(3-(triethoxysilyl)propyl)isonicotinamide using the copolymer P123 as structure-directing agent, and employed as adsorbent for the removal of alizarin red S, reactive brilliant red X-3B and reactive yellow X-RG from waste water. The adsorption measurements showed that, due to the large surface areas and the high affinity of pyridine groups, the prepared adsorbents exhibit a high adsorption capacity and an extremely rapid adsorption rate for acid dyestuffs. Using the linear forms of Langmuir, Freundlich and Redlich-Peterson isotherms, the experimental equilibrium data were analyzed. It is found that the experimental data for the adsorption of alizarin red S and reactive brilliant red X-3B can fit the Langmuir isotherm, while the Freundlich model is very suitable for describing the adsorption behavior of reactive yellow X-RG. On the basis of the Langmuir analysis, the monolayer adsorption capacities were determined to be 143.8, 891.1 and 3369.3 mg of dye per gram of adsorbent for alizarin red S, reactive brilliant red X-3B and reactive yellow X-RG, respectively. Since the pyridine unit is known as a good ligand for various metal ions, a hydrogen-bonding donor as well as an organic base, pyridine-functionalized mesoporous silica should be a promising absorbent not only for acid dyestuffs, but also for other organic and inorganic pollutants.

Ultralight, re-resistant and flexible carbon fiber aerogel is prepared by using disposable bamboo chopsticks as precursor. The aerogel can be used for oil–water separation and recycled for many times by distillation, combustion or squeeze.

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