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. 2021 Feb 18;40(11):1974–1987. doi: 10.1038/s41388-021-01682-z

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© The Author(s) 2021, corrected publication 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — Nicotine enhances CIC properties by activating the CHRNA7/JAK2/STAT3/SOX2 signaling pathway, while dextromethorphan together with metformin counteract nicotine-induced CIC properties by repressing CHRNA7/JAK2/STAT3/SOX2 signaling pathway. Mechanistically, dextromethorphan non-competitively inhibits nicotine-CHRNA7 interaction while metformin downregulates CHRNA7 by enhancing its promoter hypomethylation, and thereby they synergistically inactivating the JAK2/STAT3/SOX2 signaling pathway.