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The high incidence of colorectal cancer (CRC) is closely associated with environmental pollutant exposure. To identify potential intestinal carcinogens, we developed a cell transformation assay (CTA) using mouse adult stem cell-derived intestinal organoids (mASC-IOs) and assessed the transformation potential on 14 representative chemicals, including Cd, iPb, Cr-VI, iAs-III, Zn, Cu, PFOS, BPA, MEHP, AOM, DMH, MNNG, aspirin, and metformin. We optimized the experimental protocol based on cytotoxicity, amplification, and colony formation of chemical-treated mASC-IOs. In addition, we assessed the accuracy of in vitro study and the human tumor relevance through characterizing interdependence between cell–cell and cell–matrix adhesions, tumorigenicity, pathological feature of subcutaneous tumors, and CRC-related molecular signatures. Remarkably, the results of cell transformation in 14 chemicals showed a strong concordance with epidemiological findings (8/10) and in vivo mouse studies (12/14). In addition, we found that the increase in anchorage-independent growth was positively correlated with the tumorigenicity of tested chemicals. Through analyzing the dose–response relationship of anchorage-independent growth by benchmark dose (BMD) modeling, the potent intestinal carcinogens were identified, with their carcinogenic potency ranked from high to low as AOM, Cd, MEHP, Cr-VI, iAs-III, and DMH. Importantly, the activity of chemical-transformed mASC-IOs was associated with the degree of cellular differentiation of subcutaneous tumors, altered transcription of oncogenic genes, and activated pathways related to CRC development, including Apc, Trp53, Kras, Pik3ca, Smad4 genes, as well as WNT and BMP signaling pathways. Taken together, we successfully developed a mASC-IO-based CTA, which might serve as a potential alternative for intestinal carcinogenicity screening of chemicals. [ABSTRACT FROM AUTHOR]

Photobiomodulation therapy (PBMT) is the application of a low‐level laser device to generate physiological changes and provide therapeutic effects. Till now, the effects of PBMT on the neural differentiation of mesenchymal stem cells have been rarely reported. Herein, the potential effect and mechanism of PBMT on the neural differentiation of dental pulp stem cells (DPSCs) were preliminarily investigated in our research. The optimal dose of 3.75 J/cm2 was first screened for use in the following neural‐inducing studies. Then, DPSCs were cultured in neural induction medium and treated with laser irradiation for 7 days. From the results of morphology and immunofluorescence, we found that irradiation promoted the formation of neural stem cell‐like spheroids derived from DPSCs and enhanced potential neural differentiation. Furthermore, neural differentiation gene expressions of Nestin, microtubule‐associated protein‐2, and neural cell adhesion molecule were increased after PBMT irradiation. The protein expressions of class III β‐tubulin and neurogenic differentiation factor 1 were also improved. Meanwhile, the involvement of extracellular signal‐regulated kinase (ERK1/2) was investigated by western blot. Our study showed that the neural differentiation of DPSCs was promoted by PBMT, and the underlying mechanism in this process was associated with activating the ERK1/2 signaling pathway. [ABSTRACT FROM AUTHOR]