Effect of Food Restriction on Food Grinding in Brandt's Voles.

Food grinding is supposed to be influenced by multiple factors. However, how those factors affecting this behavior remain unclear. In this study, we investigated the effect of food restriction on food grinding in Brandt's voles (Lasiopodomys brandtii), as well as the potential role of the gut microbiota in this process, through a comparison of the variations between voles with different food supplies. Food restriction reduced the relative amount of ground food to a greater extent than it lowered the relative food consumption, and altered the abundance of Staphylococcus, Aerococcus, Jeotgalicoccus, and Un--s-Clostridiaceae bacterium GM1. Fecal acetate content for the 7.5 g-food supply group was lower than that for the 15 g-food supply group. Our study indicated that food restriction could effectively inhibit food grinding. Further, Un--s-Clostridiaceae bacterium GM1 abundance, Aerococcus abundance, and acetate content were strongly related to food grinding. Variations in gut microbial abundance and short-chain fatty acid content induced by food restriction likely promote the inhibition of food grinding. These results could potentially provide guidance for reducing food waste during laboratory rodent maintenance.

Pharmacological targeting of Axin2 suppresses cell growth and metastasis in colorectal cancer.

BACKGROUND AND PURPOSE: The scaffold molecule Axin2 is constitutively activated in colorectal cancer (CRC) and functions as a potent promoter of CRC behaviour. Pharmacological targeting of Axin2 may therefore exert a therapeutic effect in patients with CRC. Here, we discovered a potent small-molecule inhibitor of Axin2, based on the mechanism by which Axin2 is regulated post-translationally, and investigated its antitumour effects. EXPERIMENTAL APPROACH: Compound discovery and its inhibitory action on Axin2 protein were revealed by microscale thermophoresis, in vitro kinase assay, quantitative kinetic assay, immunoblotting/immunoprecipitation, RT-qPCR and cycloheximide pulse-chase assay. Compound antitumour effects and the underlying mechanisms were evaluated in multiple cell-based assays and mouse models. KEY RESULTS: We discovered that glycogen synthase kinase 3ß (GSK3ß) phosphorylates Axin2 at two consensus motifs and coupled Axin2 phosphorylation to its ubiquitination (mediated by the E3 ligase ß-Trcp2) and proteasomal degradation. The binding of Axin2 to GSK3ß in CRC cells is faint, which enables most of the Axin2 protein to maintain an unphosphorylated status and thereby permits the cells to preserve high levels of Axin2. Importantly, we identified a small-molecule compound CW85319 that enhances Axin2's interaction with GSK3ß via forming a high affinity for Axin2. Treatment of CRC cells with CW85319 enhanced Axin2 binding with GSK3ß, thereby promoting Axin2 phosphorylation, subsequent ubiquitination, and degradation. Furthermore, we demonstrated that CW85319 efficiently suppressed Axin2-driven CRC growth and metastasis, without eliciting side toxicity. CONCLUSIONS AND IMPLICATIONS: These findings suggest that pharmacological targeting of Axin2 by CW85319 may provide therapeutic benefits against certain human cancers, especially CRC.

Structural Optimization and Improving Antitumor Potential of Moreollic Acid from Gamboge.

Moreollic acid, a caged-tetraprenylated xanthone from Gamboge, has been indicated as a potent antitumor molecule. In the present study, a series of moreollic acid derivatives with novel structures were designed and synthesized, and their antitumor activities were determined in multifarious cell lines. The preliminary screening results showed that all synthesized compounds selectively inhibited human colon cancer cell proliferation. TH12-10, with an IC50 of 0.83, 1.10, and 0.79 µM against HCT116, DLD1, and SW620, respectively, was selected for further antitumor mechanism studies. Results revealed that TH12-10 effectively inhibited cell proliferation by blocking cell-cycle progression from G1 to S. Besides, the apparent structure-activity relationships of target compounds were discussed. To summarize, a series of moreollic acid derivatives were discovered to possess satisfactory antitumor potentials. Among them, TH12-10 displays the highest antitumor activities against human colon cancer cells, in which the IC50 values in DLD1 and SW620 are lower than that of 5-fluorouracil.

SIRT1 inhibitory compounds from the roots of Codonopsis pilosula.

Three new compounds, pilosulinene A (1), pilosulinols A (2), and B (3), along with seven known compounds, were isolated from the roots of Codonopsis pilosula cultivated in Xundian County of Yunnan Province. The structures of new compounds were established by spectroscopic methods. In particular, the presence of an aromatic ring in the structure of 1 makes it intriguing. The inhibitory activity of compounds against SIRT1 was evaluated. The results showed that 8 could inhibit Sirt1 in a dose-dependent manner.

Cytotoxic and N-Acetyltransferase Inhibitory Meroterpenoids from Ganoderma cochlear.

Seven compounds, including two pairs of new meroterpenoids, (+)- and (-)-gancochlearol C (1), (+)- and (-)-cochlearoid Q (3), and a new meroterpenoid gancochlearol D (2), together with four known meroterpenoids were isolated from the aqueous EtOH extract of the fruiting bodies of Ganoderma cochlear. Their structures were determined by spectroscopic data. The isolated compounds were evaluated for their cytotoxic activity against three human lung cancer cells (H1975, PC9, A549) and N-acetyltransferase inhibitory property. The results show that (+)-gancochlearol C could inhibit N-acetyltransferase with an IC50 value of 5.29 µM. In addition, ganomycin F was found to show moderate activity against the H1975 human lung cancer cell line, with an IC50 value of 19.47 µM.

Choushenosides A-C, three dimeric catechin glucosides from Codonopsis pilosula collected in Yunnan province, China.

Choushenosides A-C, three dimeric catechin glucosides, were isolated from the roots of Codonopsis pilosula cultivated at high elevations in Yunnan province of the People's Republic of China. The structures of these substances were determined by using spectroscopic and chemical methods. Biological evaluation showed that choushenoside C is a dose-dependent inhibitor of SIRT1.

Two New Triterpenoids from the Roots of Codonopsis pilosula.

Pseudolarolides U and V, two new triterpenoids, and four biogenetically related compounds, pseudolarolides E, F, K, and P were isolated from the roots of Codonopsis pilosula (Campanulaceae). Their structures were determined by spectroscopic data. The regulation of Sirtuin 1 (SIRT1) activity by all the isolated compounds was evaluated.

A Novel Flavonoid Glucoside from the Fruits of Lycium ruthenicun.

A novel flavonoid glucoside, ruthenicunoid A (1), together with eight known substances, were isolated from the fruits of Lycium ruthenicun Murr. Their structures were elucidated by extensive spectroscopic data and chemical methods. Especially, the absolute configuration of glucose residue in 1 was assigned by acid hydrolysis followed by derivatization and GC analysis. Biological evaluation towards Sirtuin 1 (SIRT1) found that compounds 1 and 2 exhibit inhibitory activity against SIRT1 in a concentration-dependent manner, indicating its potential on SIRT1-associated disorders.

Two Novel Proline-Containing Catechin Glucoside from Water-Soluble Extract of Codonopsis pilosula.

Choushenflavonoids A (1) and B (2), two unusual proline-containing catechin glucosides, were isolated from the roots of Codonopsis pilosula cultivated in a high-altitude location of Yunnan province. Their structures were determined by spectroscopic data and chemical methods. Specifically, the absolute configuration of glucose residue in 1 and 2 was assigned by acid hydrolysis followed by derivatization and gas chromatography (GC) analysis. In addition, biological evaluation of 1 and 2 against Sirtuin 1 (SIRT1) was carried out.

New ursane-type triterpenoids from Clerodendranthus spicatus.

Five new ursane-type triterpenoids, spicatusoids A-E (1, 3-6), and three known ones (2, 7, and 8), and a known oleanane-type triterpenoid (9) were isolated from the aerial parts of Clerodendranthus spicatus. Their structures were elucidated by spectroscopic methods. In particular, the structure of 3 including its absolute configuration was confirmed by single-crystal X-ray diffraction analysis. Cell viability of all the compounds against rat kidney fibroblast cells (NRK-49F) with or without TGF-ß1 induction and human cancer cells (HL-60, SMMC-7721, A-549, MCF-7, and SW-480) was examined by using MTT or MST assays. It was found that, with exception of 1, all the tested compounds could inhibit cell proliferation in TGF-ß1 induced NRK-49F cells with compounds 2 being most active.

New terpenoids from Resina Commiphora.

Three new eudesmane sesquiterpenoids, commiphoranes E1-E3 (1-3), a new podocarpane diterpenoid, commiphorane F (4), three new triterpenoids, commiphoranes G1-G3 (5-7), and fourteen known terpenoids (8-21) were isolated from Resina Commiphora. The structures and relative configurations of new compounds were mainly assigned by spectroscopic methods. In particular, the absolute configuration of 3 was clarified by computational methods. Renoprotective effects of all these isolates were evaluated by using an ELISA assay in TGF-ß1-induced rat kidney tubular epithelial cells. The present findings add new facets for chemical profiling of plant resins.

Commiphoranes A-D, Carbon Skeletal Terpenoids from Resina Commiphora.

Commiphoranes A-D (1-4), four novel aromatic terpenoids with unprecedented carbon skeletons, were isolated from Resina Commiphora. Their structures were identified by spectroscopic and crystallographic methods. Compounds 1 and 2 are dinorditerpenoids characteristic of a 6/6/6/6 ring system. In contrast, compounds 3 and 4 are sesquiterpenoids possessing a 5/6/7 backbone. Biological evaluation reveals that 3 could significantly attenuate overproduction of fibronectin, collagen I, and α-SMA in TGF-ß1-induced rat renal proximal tubular cells.

Racemic alkaloids from the fungus Ganoderma cochlear.

Seven pairs of new alkaloid enantiomers, ganocochlearines C-I (1, 3-8), and three pairs of known alkaloids were isolated from the fruiting bodies of Ganoderma cochlear. The chemical structures of new compounds were elucidated on the basis of 1D and 2D NMR data. The absolute configurations of compounds 1, 3-10 were assigned by ECD calculations. Biological activities of these isolates against renal fibrosis were accessed in rat normal or diseased renal interstitial fibroblast cells. Importantly, the plausible biosynthetic pathway for this class of alkaloids was originally proposed.

Spatially adapted total variation model to remove multiplicative noise.

Multiplicative noise removal based on total variation (TV) regularization has been widely researched in image science. In this paper, inspired by the spatially adapted methods for denoising Gaussian noise, we develop a variational model, which combines the TV regularizer with local constraints. It is also related to a TV model with spatially adapted regularization parameters. The automated selection of the regularization parameters is based on the local statistical characteristics of some random variable. The corresponding subproblem can be efficiently solved by the augmented Lagrangian method. Numerical examples demonstrate that the proposed algorithm is able to preserve small image details, whereas the noise in the homogeneous regions is sufficiently removed. As a consequence, our method yields better denoised results than those of the current state-of-the-art methods with respect to the signal-to-noise-ratio values.