No abstract

Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcinoma without timely treatment. Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing apoptosis are the main methods for the treatment of liver fibrosis. In our previous study, we found that the TOA-glycine derivative (G-TOA) had exhibited more significant inhibitory activity against HepG2 cells and better hydrophilicity than TOA, ligustrazine (TMP), and oleanolic acid (OA). However, inhibiting activated HSC proliferation and inducing apoptosis by G-TOA had not been reported. In this paper, the selective cytotoxicity of G-TOA was evaluated on HSC-T6 cells and L02 cells, and apoptosis mechanisms were explored. It was found that G-TOA could selectively inhibit the proliferation of activated HSC-T6 cells, induce morphological changes, early apoptosis, and mitochondrial membrane potential depolarization, increase intracellular free calcium levels, downregulate the expression of NF-κB/p65 and COX-2 protein, and decrease the ratio of Bcl-2/Bax, thereby inducing HSC-T6 cell apoptosis. Thence, G-TOA might be a potential antifibrosis agent for the therapy of hepatic fibrosis, provided that it exerts anti-fibrosis effects on activated HSC-T6 cells.

Unlike eutherian mammals, the colon of the Australian common brushtail possum, Trichosurus vulpecula, a metatherian mammal, is incapable of electrogenic Cl(-) secretion and has elevated levels of electrogenic Na(+) absorption, while the ileum secretes HCO (3) (-) rather than Cl(-). In eutherian mammals, the cystic fibrosis transmembrane conductance regulator (CFTR) is essential for both Cl(-) and HCO (3) (-) secretion and the regulation of Na(+) absorption. Therefore, we have sequenced possum (p)CFTR, described its distribution and characterized the properties of cloned pCFTR expressed in Fischer rat thyroid (FRT) cells. pCFTR (GenBank accession No. AY916796) has a 1,478 amino acid open reading frame, which has >90% identity with CFTR from other marsupials and >80% identity with non-rodent eutherian mammals. In pCFTR, there is a high level of conservation of the transmembrane and nucleotide binding domains although, with the exception of other marsupials, there is considerable divergence from other species in the R domain. FRT cells transfected with pCFTR express mature CFTR protein which functions as a small Cl(-) channel activated by cAMP-dependent phosphorylation. In whole-cell recordings it has a linear, time and voltage-independent conductance, with a selectivity sequence P(Br) > P(Cl) > P(I) > P(HCO)(3) >> P(Gluconate). pCFTR transcript is present in a range of epithelia, including the ileum and the colon. The presence of pCFTR in the ileum and its measured HCO (3) (-) permeability suggest that it may be involved in ileal HCO (3) (-) secretion. Why the possum colon does not secrete Cl(-) and has elevated electrogenic Na(+) absorption, despite the apparent expression of CFTR, remains to be determined.

This study evaluated the effects of valine and isoleucine supplementation in low-crude-protein (CP) diets on performance, serum parameters, and carcass traits in growing gilts. Two-hundred gilts (29.1 ± 1.7 kg) were allotted randomly to one of five diets that included a control CP (177 g kg−1) or four low-CP (135 g kg−1) diets for 45 d. The low-CP diets were added with lysine + threonine + methionine (LCM), LCM+ tryptophan (LCT), LCT + valine (LCV), or LCV + isoleucine (LCI), respectively. Non significant difference in average daily gain was obtained in gilts receiving the control, LCV, or LCI diets, which was higher than that of pigs fed the LCM or LCT diets (P < 0.05). The supplementation of crystalline tryptophan, valine, and isoleucine improved the average daily feed intake and serum levels of total protein, tryptophan, and isoleucine (linear and quadratic effects, P < 0.05) and serum valine concentration (linear effect, P < 0.05). The results indicated that the valine supplementation, or the both combination of valine and isoleucine, could further improve the performance in 29–62 kg gilts fed the 135 g kg−1 CP diet.

Crystalline amino acids (AA) supplementation allows a reduction in the dietary crude protein (CP) level maintaining pig per