Agrimoniin inhibits the activity of CYP1A2, 2D6, and 3A4 in human liver microsomes.

The effect of agrimoniin on the activity of cytochrome P450 (CYP450) enzymes would induce drug-drug interaction, which leads to adverse effects or even failure of therapy.Agrimoniin was incubated with the specific substrates of eight human liver CYP isoforms in pooled human liver microsomes. The enzyme kinetics and time-dependent study were performed to obtain kinetic parameters and characteristics in vitro.Agrimoniin significantly inhibited the activity of CYP1A2, 2D6, and 3A4 in a dose-dependent manner with IC50 values of 6.26, 9.35, and 8.30 µM, respectively. Agrimoniin served as a non-competitive inhibitor of CYP3A4 and a competitive inhibitor of CYP1A2 and 2D6. Moreover, the incubation time also significantly affected the inhibition of CYP3A4.In vitro inhibitory effect of agrimoniin on the activity of CYP1A2, 2A6, and 3A4 was reported in this study. The potential drug-drug interactions between agrimoniin and drugs metabolised by CYP1A2, 2D6, and 3A4 should be paid special attention.

Melatonin improves K+ and Na+ homeostasis in rice under salt stress by mediated nitric oxide.

Rice (Oryza sativa L.) productivity is greatly affected by soil salinity and melatonin (MLT) has long been recognized as a positive molecule that can alleviate the damage caused by salt. Here, the role of nitric oxide (NO) in the regulation of salt tolerance by MLT was investigated in rice. MLT pretreatment increased the fresh and dry weight of rice seedlings under salt stress. Its beneficial effects include less relative electrolyte leakage (REL) and better K+/Na+ homeostasis. MLT increased the activity of nitric oxide synthase (NOS). The polyamines (PAs) content and the utilization of arginine were also increased, thereby increasing NO content in salt-stressed rice seedlings. Pharmacological approach showed that NO, as a necessary downstream signaling molecule, was involved in the regulation of MLT on the K+/Na+ homeostasis of rice. Under salt stress, MLT improved the H+-pumps activities in plasma membrane (PM) and vacuole membrane (VM) in roots, MLT also increased the ATP content of rice roots by increasing the NO content of rice. Thus, the efflux of Na+ and the influx of K+ were promoted. When endogenous NO was scavenged, the regulation of K+/Na+ homeostasis by MLT was blocked. Therefore, MLT mediated K+/Na+ homeostasis of rice under salt stress by mediating NO.

Upregulated hsa_circ_0000129 expression promotes proliferation and migration of breast cancer cells.

Circular RNAs (circRNAs) are considered potential biomarkers in the pathogenesis and detection of several types of cancer. The present study aimed to investigate the role of hsa_circ_0000129 in the pathogenesis and molecular mechanism underlying breast cancer. A total of 68 pairs of breast cancer and corresponding paracancerous tissue samples, three different breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) and a normal human breast cell line (MCF-10A) were used to investigate the expression of hsa_circ_0000129. The effect of hsa_circ_0000129 on cell proliferation, migration and colony formation was assessed in MCF-7 and MDA-MB-468 cells, along with the expression of enhancer of zeste homolog 2 (EZH2). The results demonstrated that hsa_circ_0000129 expression was significantly higher in breast cancer tissues compared with normal tissues. In addition, high hsa_circ_0000129 expression was significantly associated with lymph node metastasis and a higher tumor-node-metastasis stage. Comparisons between the breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) and MCF-10A cells indicated similar results. MCF-7 cells overexpressed with hsa_circ_0000129 significantly increased cell proliferation, migration and colony formation compared with the negative control group, the effects of which were reversed following hsa_circ_0000129 knockdown in MDA-MB-468 cells. Furthermore, EZH2 expression was positively associated with hsa_circ_0000129 expression. Taken together, the results of the present study suggest that hsa_circ_0000129 may represent a promising prognostic biomarker for breast cancer. In addition, the role of hsa_circ_0000129 in breast cancer cell lines indicates a mechanism for tumorigenesis, as well as a potent target for the treatment of malignant progression.

Melatonin regulates antioxidant strategy in response to continuous salt stress in rice seedlings.

Melatonin mediates multiple physiological processes in plants and is involved in many reactions related to the protection of plants from abiotic stress. In this paper, the effect of melatonin on the antioxidant capacity of rice under salt stress was studied. Melatonin alleviated the inhibition of salt stress on the growth of rice seedlings, mainly by increasing the dry weight and fresh weight of shoots and roots. Melatonin alleviated the membrane damage caused by salt stress, which was mainly manifested by the decrease of TBARS content and the decrease of leaf and root damage. During the whole salt stress period, rice after melatonin pretreatment showed lower ROS (H2O2, O2•-,OH-) accumulation. In the early stage (1-3 d) of stress, the rice after melatonin pretreatment showed a strong increase in antioxidant enzyme activity, while in the later stage (5,7 d), it showed a strong increase in antioxidant content. During the whole period of salt stress, melatonin had a weak regulatory effect on AsA-GSH cycle. Through the above regulation process, the decreasing effect of melatonin on ROS content of rice under salt stress did not decrease with prolonged stress time in a short time (1-7 d). In conclusion, melatonin improved the antioxidant capacity of rice under continuous salt stress, and rice showed variable antioxidant strategies after melatonin pretreatment.

Exogenous melatonin alleviates salt stress by improving leaf photosynthesis in rice seedlings.

Melatonin (MT), an important antioxidant existing in plants and animals, has been widely reported to participate in the process of plants coping with stress. In this study, we demonstrated the mechanism of MT enhancing photosynthesis in rice under salt stress. The results showed that MT treatment increased relative water content, sucrose and starch content of rice under salt stress. This was mainly owing to the fact that MT enhanced the net photosynthetic rate and enhanced the absorption and transmission of light energy. The effect of MT on photosynthesis of rice under salt stress conditions was mainly due to the regulation of three processes: maintaining low ROS status by improving the total antioxidant capacity, promoting the xanthophyll cycle and increasing the xanthophyll pool size to dissipate excess light energy, increasing the activities of key photosynthetic enzymes. Taken together, these results provide a mechanism for MT to improve the photosynthetic capacity of rice under salt stress.