## 4 Discussion
It was then observed that glycine had ameliorated this phenomenon [40]. Additionally, in a study that was conducted in an animal model (mice), the effect of NaF on an increase in ROS generation was also observed [41]. In turn, [PERSON] et al. [42] noted that exposure to fluoride in a concentration range of 0.25-2.00 mM caused an increase in the _Nrf2_ expression in mice due to endoplasmic reticulum stress, but that a higher concentration of fluoride (4.00 mM) led to its significant down-regulation. Moreover, our findings demonstrate that an SMF may reduce the expression of the _KEAP1_ gene, which may also have an influence on the activation of the Nrf2 factor. This is quite a controversial issue, and scientific reports on this topic conflict. [PERSON] et al. [43] showed that an SMF increased the ROS level in mesenchymal stem cells. This is in contrast to our observations. However, the same authors showed an increase in the expression of Nrf2 and the antioxidant enzymes, which indicates an improvement in the antioxidant system. This situation could arise from the activation of the defense system of cells in response to increased ROS production [43]. However, [PERSON] et al. [44] proved that in fibroblast cells (NIH3T3), an SMF caused a decrease in ROS level and thus reduced the oxidative stress. In our report, the proposed mechanism for regulating the expression of the above-mentioned genes under the influence of both chemical and physical factors is the use of miRNA molecules. These small regulatory non-coding RNAs regulate various cellular signaling pathways, which helps to maintain the proper functioning of cells. However, changes in the miRNA expression profile can lead to a dysregulation of the cellular signaling pathways and the subsequent development of various diseases. On the other hand, it provides the opportunity to use them as potential diagnostic and therapeutic biomarkers. Many studies have shown the crucial role of miRNAs in regulating the Nrf2 signaling pathway as well. As was indicated in this report, selected miRNAs are involved in regulating _NFE2L2_ and _KEAP1_ activity in fibroblasts in the presence of fluoride and a static magnetic field of a moderate intensity. A negative correlation between the expression of the _NFE2L2_ gene and miR-28-3p or miR-29b-1-5p confirms their roles in regulating this gene. This may suggest the usefulness of the tested miRNAs that regulate _NFE2L2_ as potential biomarkers of the toxic effects of fluoride. A similar relationship was observed for _KEAP1_ and miR-141-3p. [PERSON] et al. [45] also demonstrated a dependence between _KEAP1_ and its regulatory miRNA. MiR-141-3p overexpression has been shown to attenuate the effects of oxidative stress in patients' liver cells [44]. Moreover, [PERSON] et al. [46] showed that the activation of Nrf2 caused breast cancer cell growth. At the same time, an overexpression of miR-29b-1-5p caused the opposite effect, including increased ROS production. To summarize, miR-29b-1-5p is down-regulated by Nrf [45]. Interestingly, the team of [PERSON] et al. [47] also found a correlation between the Nrf2 mRNA level and miR-28 expression in breast epithelial cells, but through a Keap1-independent mechanism. The up-regulation of Nrf2 mRNA via the inhibition of miR-28 was also demonstrated by [PERSON] and [PERSON] [48] in Hep2G cells after diterpene quinone-cryptotanshinone treatment. However, in our study, there was no correlation between Nrf2 and miR-365a-3p expression in the cells that had been co-treated with both factors. The role of the miR-365a-3p/Nrf2 axis was also investigated by [PERSON] et al. [49] in non-small-cell lung cancer. In turn, they showed that the metallothioneein 1D pseudogene could induce ferprotosis that was mediated by the miR-365a-3p/Nrf2 signaling pathway. These reports suggest that the miRNAs that regulate the Nrf2 pathway could be susceptible to changes in expression under the influence of natural bioactive compounds, physical factors or other agents.