Gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression- and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner

Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1-/-) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy.

Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The

Identification and characterization of MYC transcription factors in Taxus sp.

Myelocytomatosis (MYC) transcription factors (TFs) are key regulators of the jasmonic acid (JA) signaling pathway. In cell cultures, methyl jasmonate (MeJA) can improve the production of taxol, which is a complex terpenoid compound with an intense antitumor activity. However, the functions of MYC genes in Taxus sp. (yew trees) remain poorly known. Based on Taxus sp. transcriptome changes induced by MeJA, a TcMYC gene was isolated in a previous study. Here, we further characterized the TcMYC TF encoded by that gene and four other yew MYC TFs previously obtained. Three yew MYC TFs had the typical basic helix-loop-helix (bHLH)-MYC_N region, but the other two MYC did not, although all five presented the bHLH domain. TcMYC was localized to the nuclei, and phylogenetic analysis indicated that the yew MYC TFs were closely related to Arabidopsis thaliana MYC1/2 and maize R protein. The yeast one-hybrid assay showed that TcMYC binds the G-box of the promoter of taxane 5α-hydroxylase. Transcript levels of TcMYC revealed that TcMYC was highly expressed in xylem and leaves, and up-regulated by drought and high-salinity stresses. Coronatine (COR) has recently been used as a new elicitor to improve the production of taxol in cell cultures; TcMYC was strongly expressed at 2 and 4 h after COR treatment, but decreased at 12 and 24 h. Overall, the results obtained here provide new insights into the potential regulatory roles of MYC TFs on taxol biosynthesis in yew trees.