Melatonin reduced colon inflammation but had no effect on energy metabolism in ageing Mongolian gerbils (Meriones unguiculatus).

In photoperiod-sensitive wild animals, the secretion of melatonin (MT) is modulated by external photoperiod, and MT affects inflammation and the ageing process. The beneficial effects of MT in delaying the progress of ageing have been reported in laboratory mice and rats. However, little is known about MT in wild mammals. In the current study, we investigated energy metabolism, microbial community structure and colon homeostasis in ageing Mongolian gerbils (Meriones unguiculatus) through exogenous supplementation of MT to test the hypothesis that MT has beneficial effects on gut homeostasis in ageing gerbils. Exogenous MT supplementation had no effect on energy metabolism in Mongolian gerbils but reduced the levels of circulating tumor necrosis factor-α (TNF-α), immune globulin G (IgG) and corticosterone (CORT). The increase in the level of inflammation in ageing animals was related to changes in the structure and diversity of the gut microbiota. At the genus level, the relative abundance of Prevotella, Treponema, Corynebacterium, and Sphingomonas was increased in ageing animals and decreased significantly by the treatment of MT. Christensenella and Lactobacillus were attenuated in ageing animals, and tended to be enhanced by MT treatment. Functions related to glycosphingolipid biosynthesis-ganglio series and lipopolysaccharide biosynthesis (metabolisms of cofactors, vitamins and glycan) were increased in ageing animals and decreased significantly by the treatment of MT. Our data suggest that a supplement of MT could improve colon homeostasis through changing the composition of gut microbiota and reducing inflammation in ageing gerbils.

Activation of RAS/ERK alone is insufficient to inhibit RXRα function and deplete retinoic acid in hepatocytes.

Activation of RAS/ERK signaling pathway, depletion of retinoid, and phosphorylation of retinoid X receptor alpha (RXRα) are frequent events found in liver tumors and thought to play important roles in hepatic tumorigenesis. However, the relationships among them still remained to be elucidated. By exploring the transgenic mouse model of hepatic tumorigenesis induced by liver-specific expression of H-ras12V oncogene, the activation of RAS/ERK, the mRNA expression levels of retinoid metabolism-related genes, the contents of retinoid metabolites, and phosphorylation of RXRα were determined. RAS/ERK signaling pathway was gradually and significantly activated in hepatic tumor adjacent normal liver tissues (P) and hepatic tumor tissues (T) of H-ras12V transgenic mice compared with normal liver tissues (Wt) of wild type mice. On the contrary, the mRNA expression levels of retinoid metabolism-related genes were significantly reduced in P and T compared with Wt. Interestingly, the retinoid metabolites 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (atRA), the well known ligands for nuclear transcription factor RXR and retinoic acid receptor (RAR), were significantly decreased only in T compared with Wt and P, although the oxidized polar metabolite of atRA, 4-keto-all-trans-retinoic-acid (4-keto-RA) was significantly decreased in both P and T compared with Wt. To our surprise, the functions of RXRα were significantly blocked only in T compared with Wt and P. Namely, the total protein levels of RXRα were significantly reduced and the phosphorylation levels of RXRα were significantly increased only in T compared with Wt and P. Treatment of H-ras12V transgenic mice at 5-week-old or 5-month-old with atRA had no effect on the prevention of tumorigenesis or cure of developed nodules in liver. These events imply that the depletion of 9cRA and atRA and the inhibition of RXRα function in hepatic tumors involve more complex mechanisms besides the activation of RAS/ERK pathway.

Endogenous glucocorticoid increases the basal level of Treg-Th17 balance under early phase of stress.

OBJECTIVE: To explore the changes of Treg-Th17 balance influenced by corticosterone, major effect hormone of hypothalamic-pituitary-adrenal (HPA) axis under running stress. METHODS: A total of 25 corticotropin-releasing hormone (CRH) wildtype (CRH+/+) and knockout (CRH-/-) mice were adopt and divided into 4 groups as follows: CRH+/+ ctrl, CRH+/+ stress, CRH-/- ctrl and CRH-/- stress. All mice in stress groups were under 2 h running. After 1 h, blood plasma in all groups was collected and the expression of corticosterone and IL-17A was detected by ELISA. Meanwhile, unicell suspensions of peripheral lymph node and spleen in each group were prepared too and stained by PE-CD4 and FITC-CD25, then the changes of Treg (CD4+CD25+) in different groups were checked by flow cytometry; all data were statistically analyzed by the software of WinMDI 2.9, SPSS 11.5, Origin 7.5 and Matlab 2-D and 3-D plot function. RESULTS: The levels of corticosterone were significantly higher in stress groups than that in corresponding control groups (P less than 0.05), especially in CRH+/+ stress group (P less than 0.01). However, the changes of Tregs were not obvious between stress groups and control groups with respective genotypes (P less than 0.05). Compared with that in CRH+/+ control group, the ratio of Treg and the expression of IL-17A in CRH-/- stress group were significantly higher than those in control group (P less than 0.05). Combined with the expression levels of corticosterone, Treg and Th17, our study suggests that endogenous glucocorticoid with basal level may cause the changes in Treg-Th17 balance. Moreover, as the corticosterone level increases, the expression of Treg and Th17 appears to manifest antagonistic fluctuant status with a rising tendency in general. CONCLUSION: Endogenous glucocorticoid under early stage of stress may increase the function of T lymphocyte immunity to some extent.

Noise-reduced electroless deposition of arrays of copper filaments.

We report here a self-organized electroless deposition of copper in an ultrathin layer CuSO4 of electrolyte. Microscopically the branching rate of the copper deposits is significantly decreased, forming an array of smooth polycrystalline filaments. Compared with a conventional electrodeposition system, no macroscopic electric field is involved and the thickness of the electrolyte layer is greatly decreased. Therefore the electroless deposition takes place in a nearly ideal, two-dimensional diffusion-limited environment. We suggest that restriction of the thickness of the electrolyte film is responsible for the generation of smoother branches of the electrodeposits. Our data also show that even in a diffusion-limited scenario the aggregate morphology is not necessarily very ramified and fractal-like.