[Effect of electroacupuncture on morphine-conditioned place preference and activation of glutamatergic neurons in the ventromedial prefrontal cortex in rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) and "Sanyinjiao"(SP6) on conditioned place preference (CPP) and activation of glutamatergic neurons in the ventromedial prefrontal cortex (VMPFC) of morphine-addiction rats, so as to explore its mechanisms underlying detoxification. METHODS: Thirty male SD rats were randomly and equally divided into control, model and EA groups. The rats with acquisition of morphine-induced CPP received intraperitoneal injection of morphine (10 mg/kg) in the morphine-paired chamber, once daily for 3 consecutive days, and those of the control group received intraperitoneal injection of the same dose of normal saline in saline-paired chamber. Thirty minutes before CPP acquisition training, EA (2 Hz/100 Hz, 0.5 to 1.0 mA) was applied to ST36 and SP6 for 20 min every day. The double-labeled neurons of Fos/vesicular glutamate transporter 2 (VGLUT2) in the VMPFC were detected by using fluorescent immunohistochemistry. The discharges of the VMPFC neurons were recorded by using a multi-channel microarray electrophysiological system, followed by performing a z-score standardized processing. The ratio of firing rate frequency of rats in the morphine-paired chamber/saline-paired chamber was calculated, and further statistical analysis was conducted on the data based on the standardized z-scores. The neuronal firing characteristic of glutamatergic neuron is low frequency and wide wave. RESULTS: Compared with the control group, the score of morphine-induced CPP and numbers of Fos, VGLUT2-positive and Fos-VGLUT2 double-labeled positive cells were significantly increased in the model group (P<0.01，P<0.05). After EA and in comparison with the model group, the morphine CPP score and numbers of Fos, VGLUT2-positive and Fos-VGLUT2 double-labeled cells were significantly reduced in the EA group (P<0.01，P<0.05). The ratio of firing rate of the VMPFC neurons in the preference chamber and the percentage of inhibitory neurons as well as the z-score were considerably lower in the EA group than in the model group (P<0.001). CONCLUSION: EA can suppress morphine-induced seeking behavior in rats, which may be related to its inhibitory effect on glutamatergic neurons in the VMPFC.

Genistein inhibits nasopharyngeal cancer stem cells through sonic hedgehog signaling.

Genistein, a soy derived isoflavanoid compound, exerts anticancer effects in various cancers. Nasopharyngeal cancer stem cells (NCSCs) are a small subpopulation of cancer cells which are responsible for initiation, progression, metastasis, and recurrence of nasopharyngeal cancer. The present study aimed to investigate the suppressive effects of genistein on NCSCs and its underlying mechanism. NCSCs were enriched from human nasopharyngeal cancer cell lines CNE2 and HONE1 through tumorsphere-forming assay. It was shown that genistein inhibited the tumorsphere formation capacity, decreased the number of EpCAM+ cells, downregulated the expression of NCSCs markers, suppressed cell proliferation, and induced apoptosis of NCSCs. Genistein suppressed the activity of Sonic hedgehog (SHH) signaling, which was important for the maintenance of NCSCs, while activation of SHH signaling by purmorphamine diminished the inhibitory effects of genistein on NCSCs. Our data suggested that genistein inhibited NCSCs through the suppression of SHH signaling. These findings support the use of genistein for targeting NCSCs.

Phenethyl isothiocyanate inhibits colorectal cancer stem cells by suppressing Wnt/ß-catenin pathway.

Cancer stem cells (CSCs) are considered to play essential roles in the process of origination, proliferation, migration, and invasion of cancer, and their properties are regulated by Wnt/ß-catenin pathway. Phenethyl isothiocyanate (PEITC) is a natural product obtained from cruciferous vegetables with anticancer activities. The present study aimed to investigate the inhibitory effect and the underlying mechanisms of PEITC on colorectal CSCs. In this study, we found that PEITC can significantly reduce the size and number of colorectal cancer cell spheroids in serum-free medium. With increasing PEITC concentrations (10-40 µM), the number of spheroids was reduced to about 10% of the control group, and the percentage of CD133+ cells was decreased by about 3-16 folds. PEITC also decreased the expression of CSC markers. Meanwhile, inhibition of proliferation as well as induction of apoptosis of colorectal CSCs was observed after PEITC treatment. Furthermore, through activating Wnt/ß-catenin pathway with LiCl, the inhibitory effects of PEITC on colorectal CSCs were diminished. Our data suggested that PEITC can be an effective inhibitor of colorectal CSCs by targeting Wnt/ß-catenin pathway.