The imbalanced expression of matrix metalloproteinases (MMPs) is associated with liver fibrosis, one of the most common chronic liver diseases. Enhanced expression of MMPs by gene therapy is emerging as a promising antifibrotic strategy, but the effectiveness of this approach depends on reliable systems for delivering MMP genes. Here, we evaluated a newly designed hyaluronic acid (HA)-shielded delivery system for systemic administration of plasmid DNA encoding MMP13 (pMMP13), and tested whether the enhanced expression of MMP13 ameliorates liver fibrosis in mice. In the CCl(4)-induced liver fibrosis model, systemic administration of pMMP13 using HA and polyethylenimine (PEI) significantly increased the expression of MMP13 and reduced collagen deposition. Moreover, following delivery of pMMP13 in a HA-shielded PEI complex, the serum levels of aspartate transaminase were reduced to levels approaching those in untreated normal mice. These results indicate that the delivery of pMMP13 using HA-shielded PEI enhances the efficiency of MMP13 expression in the liver, and highlight the potential of pMMP13 gene therapy as an antifibrotic strategy.
This study investigated the effects of different diet concentrate levels in animal diets as a source of rumen fluid inoculum for in vitro ruminal fermentation, CH 4 concentration, and methanogen abundance and diversity. Three non-lactating mature cows assigned to a 3 Â 3 Latin square design were fed with Italian rye grass and concentrate feed at 2 (low), 5 (medium), and 8 (high) kg per animal per day were used as rumen fluid donors. The experiment consisted of three 21-d periods that each consisted of 14 d adaptation followed by 7 d of continuous feeding prior to rumen fluid collection for in vitro fermentation evaluation. High concentrate proportion produced the highest total gas in all incubation periods (p < .05) while methane (CH 4 ) concentration was highest in low concentrate proportions and lowest in medium concentrate proportions. Propionate concentration was highest in high concentrate proportions, whereas butyrate concentration was highest in medium concentrate proportions. High concentrate proportion at 0 and 12 h and medium concentrate proportions at 12 h produced archaeal denaturing gradient gel electrophoresis (DGGE) profiles that differed from those of low concentrate proportions. Medium concentrate proportion had the lowest methanogen DNA copies at 12 h of incubation (p < .05). Changes in diet influenced the rumen microbiome, CH 4 concentration, and methanogen diversity and abundance in cattle. The rumen conditions of an animal, as along with the microbiome, change as the feed diet changes. As a result, the inoculum for in vitro rumen fermentation studies affects Volatile fatty acid (VFA) concentrations, CH 4 production, and methanogen diversity and abundance.
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