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Background: Crocin, an active constituent of saffron, has anticancer activity. In this study, we investigated the relationship of Crocin with human gastric epithelial cells induced by 1-methyl-3-nitroso-1-nitroguanidine (MNNG), and explored the underlying mechanism. Methods: In vivo, the animal growth and atypical hyperplasia were observed in Sprague-Dawley rats. A cell model was established by treating the human gastric mucosa epithelial cell line GES-1 with MNNG.The effects of Crocin on proliferation, cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT) in GES-1 cells were analyzed using Cell Counting Kit-8, colony formation, flow cytometry, and Transwell assay, respectively. Western blot was used to explore the potential mechanism.. Results: The gastric mucosa of animal model deteriorated obviously, the weight growth rate slowed down, and the atypical hyperplasia of gastric mucosa increased. The GES-1 cells had characteristics of malignant cells such as proliferation, apoptosis, and metastasis ability. It was found that Crocin suppressed the cell proliferation, increased apoptosis, and blocked the cycle arrest in G0/G1 phase simultaneously. Furthermore, Crocin negatively regulated the invasion ability of MNNG-treated GES-1 cells and EMT process. Crocin also increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), decreased TAZ in MNNG-treated GES-1 cells. Interestingly, Crocin regulated the expression of TAZ and yes-associated protein (YAP) by increasing Nrf2 level, as well as their upstream targets, mercaptopyruvate sulfurtransferase (MST) and large tumor suppressor (LATS). Conclusions: Crocin protected against MNNG-induced malignant transformation through the Nrf2/ Hippo signaling pathway, which might be a drug candidate for clinical gastric cancer management.

Due to the extremely low permeability and the excellent creep behavior, rock salt is the optimal surrounding rock of underground energy storage. The long-term safe operation of the rock salt energy storage is closely related to the creep behavior and long-term strength of rock salt, but few researches focus on the long-term strength of rock salt. In order to more accurately predict the long-term strength of rock salt, the isochronous stress–strain curve method and the volume expansion method for determining the long-term strength were analyzed and discussed based on axial compression tests and axial creep tests. The results show that the isochronous stress–strain curve method is intuitive but will greatly increase the test cost and test time to obtain a satisfactory result. The volume expansion method is simple, but the long-term strength obtained according to the inflection point of volumetric strain is much greater than the actual long-term strength of rock salt. Therefore, a new method applicable to rock salt was proposed based on the evolution of damage in rock salt in this paper, which takes the corresponding stress value at the damage initiation point as the long-term strength. The long-term strength determined by this method is consistent with that by the isochronous stress–strain curve method. The method is more economical and convenient and aims to provide a reference for the long-term stability study of underground salt caverns.