Tetramethylpyrazine-Rhein Derivative inhibits the migration of canine inflammatory mammary carcinoma cells by mitochondrial damage-mediated apoptosis and cadherins downregulation.

BACKGROUND: Canine inflammatory mammary carcinoma (CIMC) has a high incidence of metastasis, high lethality, and poor prognosis, which needs novel adjuvant agents. Tetramethylpyrazine-Rhein Derivative (TRD) has been shown to have antitumor activity, which is a potential research direction for CIMC. PURPOSE: This study evaluated the efficacy of TRD on CIMC in vitro and in vivo, and provided possibilities for the application of active compounds in traditional Chinese medicine. METHODS: In vitro, TRD cytotoxicity was measured with CCK-8. Flow cytometry and transmission electron microscope were used to detect the cell cycle, cell death, and changes in mitochondria. Wound-healing assay, cell invasion assay, and scanning electron microscope were used to evaluate the suppression of cell migration and invasion. Expression changes were detected by RT-qPCR and western blot assay. In vivo, the lung metastasis models were randomly divided into control, low-dose TRD, high-dose TRD, and positive groups. Each group was administered orally once a day for 18 days and took in vivo imaging photos. RESULTS: The IC50 of TRD in CHMp and MDCK were 42.59 and 79.37 µM, respectively. TRD mediated cell apoptosis by mitochondrial damage and caused S and G2/M phase arrest by downregulating cyclin B1. Moreover, TRD reduced filopodia and inhibited cell migration by downregulating cadherins. In CIMC lung metastasis models, TRD could effectively inhibit tumor growth (P < 0.001) in the lungs without significant toxicity. CONCLUSION: TRD showed potential activity to inhibit CIMC lung metastasis with multi-target and low toxicity.

The Impact of Air Pollution on the Protection of World Cultural Heritage in China.

The damage of air pollution to cultural heritage is widely known. However, the quantitative effects still need to be explored at a holistic level. Different from existing research which focuses on the "model calculation" methods, this paper uses an econometric approach to assess the overall impact of air pollution on the sustainable protection of world cultural heritage in China. Based on the data of the annual monitoring report from 2014 to 2020 released by the China World Cultural Heritage Monitoring Platform, this paper uses the thermal inversion as an instrument variable of air pollution to estimate the overall effects of air pollution on all world cultural heritage sites in China. The results indicate that almost all the air pollutants (except for CO) have significantly negative effects on heritage. The damaging effects of gaseous pollutants including SO2, NO2 and O3 is greater than that of particulate pollutants such as PM2.5 and PM10. Rainfall can exacerbate the worsening effects of gaseous pollutants, but will mitigate the negative effects of particulate pollutants; the windy weather may weaken the negative impact. In addition, environmental regulations from the local government can also alleviate the negative influence of air pollution on heritage protection. This research can provide a more comprehensive environmental prevention policy reference for the protection of world cultural heritage.