Methamphetamine abuse is a major public health crisis. Because accumulating evidence supports the hypothesis that the gut microbiota plays an important role in central nervous system (CNS) function, and research on the roles of the microbiome in CNS disorders holds conceivable promise for developing novel therapeutic avenues for treating CNS disorders, we sought to determine whether administration of methamphetamine leads to alterations in the intestinal microbiota. In this study, the gut microbiota profiles of rats with methamphetamine-induced conditioned place preference (CPP) were analyzed through 16S rRNA gene sequencing. The fecal microbial diversity was slightly higher in the METH CPP group. The propionate-producing genus Phascolarctobacterium was attenuated in the METH CPP group, and the family Ruminococcaceae was elevated in the METH CPP group. Short chain fatty acid analysis revealed that the concentrations of propionate were decreased in the fecal matter of METH-administered rats. These findings provide direct evidence that administration of METH causes gut dysbiosis, enable a better understanding of the function of gut microbiota in the process of drug abuse, and provide a new paradigm for addiction treatment.

There are divergences between neuropathic pain and visceralgia in terms of the duration, location, and character of hyperalgesia. It is generally recognized that nociceptive receptors, including P2X receptors, may play different roles in nociceptive mechanisms. The different roles of P2X1-7 receptors have not been fully understood both in neuropathic pain and visceral hyperalgesia. In order to explore the different expressions of P2X1-7 receptors in these two hyperalgesia models, the lumbosacral dorsal root ganglion (DRG) neurons from rat sciatic nerve chronic constriction injury (CCI) model and neonatal colorectal distention (NCRD) model were studied (both the primary nociceptive neuron afferents of those two models projected to the same segment of spinal cord). Both immunohistochemistry (IHC) technique and real-time fluorescence quantitative polymerase chain reaction (RT-PCR) technology were applied to analyze the protein expression levels and nucleic acid of P2X1-7 receptors. We found that except P2X2 and P2X3, the expression levels of P2X1 and P2X5 receptors increased in neuropathic pain while those expression levels of P2X4, P2X6, and P2X7 receptors increased in visceral pain. Our results also suggested that in addition to P2X2/3 heteromeric, other P2X subunits may also involved in generation heteromeric such as P2X1/5 and/or P2X2/5 in neuropathic pain and P2X4/6 and/or P2X4/7 in visceral pain.

Previous investigations have demonstrated that ginsenoside Rg3 (Rg3) has many actions including antitumor, antioxidative, and immunomodulatory effects. However, Rg3 exists as 2 stereoisomeric pairs, 20(S)-ginsenoside Rg3 [20(S)-Rg3] and 20(R)-ginsenoside Rg3 [20(R)-Rg3], which have disparate pharmacological actions because of their different chemical structures. In this study, the 2 epimers were compared for their effects on the growth of hepatocellular carcinoma H22 transplanted tumors and the immune function of H22-bearing mice. In vivo efficacy study showed that the growth of H22 transplanted tumors was significantly inhibited when treated with 20(S)-Rg3 and 20(R)-Rg3 (P < 0.05), and the inhibition rate of tumor growth was 23.6% and 40.9%, respectively. Furthermore, the cellular immunity of H22-bearing mice was remarkably enhanced after Rg3 treatment (P < 0.05), which may be due to stimulation of ConA-induced lymphocyte proliferation and augmentation of Th1-type cytokines interleukin-2 and interferon-γ levels in mice. Interestingly, the effects of 20(R)-Rg3 were significantly greater than those of the S-form (P < 0.05). Taken together, these results indicate that Rg3 inhibits H22 tumor growth in vivo at least partly by improving the host's cellular immunity in a stereospecific manner, and 20(R)-Rg3 is more potent for treating cancers or other immune-mediated diseases clinically.

Abstract. accumulating evidence has proved that potassium channels (K + channels) are involved in regulating cell proliferation, cell cycle progression and apoptosis of tumor cells. However, the precise cellular mechanisms are still unknown. in the present study, we investigated the effect and mechanisms of quinidine, a commonly used voltage-gated K + channel blocker, on cell proliferation and apoptosis of human glioma U87-MG cells. We found that quinidine significantly inhibited the proliferation of u87-Mg cells and induced apoptosis in a dose-dependent manner. the results of caspase colorimetric assay showed that the mitochondrial pathway was the main mode involved in the quinidine-induced apoptotic process. furthermore, the concentration range of quinidine, which inhibited voltage-gated K + channel currents in electrophysiological assay, was consistent with that of quinidine inhibiting cell proliferation and inducing cell apoptosis. in u87-Mg cells treated with quinidine (100 µmol/l), 11 of 2,042 human micrornas (mirnas) were upregulated and 16 were downregulated as detected with the mirna array analysis. the upregulation of mir-149-3p and downregulation of mir-424-5p by quinidine treatment were further verified by using quantitative real-time PCR. In addition, using mirna target prediction program, putative target genes related to cell prolif eration and apoptosis for two differentially expressed mirnas were predicted. taken together, these data suggested that the anti-proliferative and pro-apoptosis effect of voltage-gated K + channel blocker quinidine in human glioma cells was mediated at least partly through regulating expression of mirnas, and provided further support for the mechanisms of voltage-gated K + channels in mediating cell proliferation and apoptosis.

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