New Insight into the Function of Dopamine (DA) during Cd Stress in Duckweed (Lemna turionifera 5511).

Dopamine (DA), a kind of neurotransmitter in animals, has been proven to cause a positive influence on plants during abiotic stress. In the present study, the function of DA on plants under cadmium (Cd) stress was revealed. The yellowing of duckweed leaves under Cd stress could be alleviated by an exogenous DA (10/20/50/100/200 µM) supplement, and 50 µM was the optimal concentration to resist Cd stress by reducing root breakage, restoring photosynthesis and chlorophyll content. In addition, 24 h DA treatment increased Cd content by 1.3 times in duckweed under Cd stress through promoting the influx of Cd2+. Furthermore, the gene expression changes study showed that photosynthesis-related genes were up-regulated by DA addition under Cd stress. Additionally, the mechanisms of DA-induced Cd detoxification and accumulation were also investigated; some critical genes, such as vacuolar iron transporter 1 (VIT1), multidrug resistance-associated protein (MRP) and Rubisco, were significantly up-regulated with DA addition under Cd stress. An increase in intracellular Ca2+ content and a decrease in Ca2+ efflux induced by DA under Cd stress were observed, as well as synchrony with changes in the expression of cyclic nucleotide-gated ion channel 2 (CNGC2), predicting that, in plants, CNGC2 may be an upstream target for DA action and trigger the change of intracellular Ca2+ signal. Our results demonstrate that DA supplementation can improve Cd resistance by enhancing duckweed photosynthesis, changing intracellular Ca2+ signaling, and enhancing Cd detoxification and accumulation. Interestingly, we found that exposure to Cd reduced endogenous DA content, which is the result of a blocked shikimate acid pathway and decreased expression of the tyrosine aminotransferase (TAT) gene. The function of DA in Cd stress offers a new insight into the application and study of DA to Cd phytoremediation in aquatic systems.

Acetylcholine (ACh) enhances Cd tolerance through transporting ACh in vesicles and modifying Cd absorption in duckweed (Lemna turionifera 5511).

Acetylcholine (ACh), an important neurotransmitter, plays a role in resistance to abiotic stress. However, the role of ACh during cadmium (Cd) resistance in duckweed (Lemna turionifera 5511) remains uncharacterized. In this study, the changes of endogenous ACh in duckweed under Cd stress has been investigated. Also, how exogenous ACh affects duckweed's ability to withstand Cd stress was studied. The ACh sensor transgenic duckweed (ACh 3.0) showed the ACh signal response under Cd stress. And ACh was wrapped and released in vesicles. Cd stress promoted ACh content in duckweed. The gene expression analysis showed an improved fatty acid metabolism and choline transport. Moreover, exogenous ACh addition enhanced Cd tolerance and decreased Cd accumulation in duckweed. ACh supplement reduced the root abscission rate, alleviated leaf etiolation, and improved chlorophyll fluorescence parameters under Cd stress. A modified calcium (Ca2+) flux and improved Cd2+ absorption were present in conjunction with it. Thus, we speculate that ACh could improve Cd resistance by promoting the uptake and accumulation of Cd, as well as the response of the Ca2+ signaling pathway. Also, plant-derived extracellular vesicles (PDEVs) were extracted during Cd stress. Therefore, these results provide new insights into the response of ACh during Cd stress.

Aphthous ulcer drug inhibits prostate tumor metastasis by targeting IKKɛ/TBK1/NF-κB signaling.

Tumor metastasis is the major cause of death for prostate cancer (PCa) patients. However, the treatment options for metastatic PCa are very limited. Epithelial-mesenchymal transition (EMT) has been reported to be an indispensable step for tumor metastasis and is suggested to associate with acquisition of cancer stem cell (CSC) attributes. We propose that small-molecule compounds that can reverse EMT or induce mesenchymal-epithelial transition (MET) of PCa cells may serve as drug candidates for anti-metastasis therapy. Methods: The promoters of CDH1 and VIM genes were sub-cloned to drive the expression of firefly and renilla luciferase reporter in a lentiviral vector. Mesenchymal-like PCa cells were infected with the luciferase reporter lentivirus and subjected to drug screening from a 1274 approved small-molecule drug library for the identification of agents to reverse EMT. The dosage-dependent effect of candidate compounds was confirmed by luciferase reporter assay and immunoblotting. Wound-healing assay, sphere formation, transwell migration assay, and in vivo intracardiac and orthotopic tumor xenograft experiments were used to evaluate the mobility, metastasis and tumor initiating capacity of PCa cells upon treatment. Possible downstream signaling pathways affected by the candidate compound treatment were analyzed by RNA sequencing and immunoblotting. Results: Drug screening identified Amlexanox, a drug used for recurrent aphthous ulcers, as a strong agent to reverse EMT. Amlexanox induced significant suppression of cell mobility, invasion, serial sphere formation and in vivo metastasis and tumor initiating capacity of PCa cells. Amlexanox treatment led to downregulation of the IKK-ɛ/ TBK1/ NF-κB signaling pathway. The effect of Amlexanox on EMT reversion and cell mobility inhibition can be mimicked by other IKK-ɛ/TBK1 inhibitors and rescued by reconstitution of dominant active NF-κB. Conclusions: Amlexanox can sufficiently suppress PCa metastasis by reversing EMT through downregulating the IKK-ɛ/TBK1/NF-κB signaling axis.

[Hypolipidemic effect of Coptis chinensis and C. deltoidea on type 2 diabetes rats through SCAP/SREBP-1c signal pathway].

The type 2 diabetes rat model was induced with high-sugar and high-fat diet combined with low-dose STZ. This study investigated the hypolipidemic mechanism of Coptis chinensis and C. deltoidea. After 30 days of administration, HOMA-IR and the content of TG in serum were detected, and the expressions of SCAP, SREBP-1c were tested by the method of Western blot and Real-time PCR analysis. The test results showed that both components can significantly alleviate insulin resistance and down-regulate the expressions of SREBP-1c and SCAP in liver tissue of type two diabetes mellitus. Compared with the control group, there were significant differences in relevant protein expression (P<0.05, P<0.01). This indicates that the inhibition of SREBP-1c and SCAP expressions may be the hypolipidemic mechanism of Coptidis Rhizoma on type 2 diabetes mellitus. The results also showed that C. deltoidea has a better efficacy in lipid elimination, but a weaker hypoglycemic effect against C. chinensis.