We have developed novel proteinase-modulated contrast agents (PCAs) to detect the activity of proteinases in vivo using magnetic resonance imaging. The PCAs are based on the concept of a solubility switch, from hydrophilic to hydrophobic, that significantly modifies the pharmacokinetic properties of the agent as revealed by the slow efflux kinetics from the activity site. Our compound PCA7-switch detects the activity of the secreted matrix-degrading proteinase matrix-metalloproteinase 7 (MMP-7) in living, tumor-bearing mice. Control experiments were performed using an agent that was not cleaved by MMP-7 (PCA7-scrambled), an agent that could be cleaved by MMP-7 but lacked the solubility switch (PCA7-B), and a standard contrast agent (gadolinium-diethylenetriaminepentaacetic acid). PCA7-switch detected a reduction in MMP-7 activity in tumor-bearing mice treated with a synthetic MMP inhibitor, demonstrating its effectiveness in noninvasive functional imaging of proteolytic activity in vivo.
In
this study, Pediococcus pentococcus PP04 isolated from the Northeast pickled cabbage had good gastrointestinal
tolerance and can colonize in the intestine stably. C57BL/6N mice
were fed a high-fat diet to build animal models and treated with Pediococcus pentosaceus PP04 to evaluate the antihyperlipidemia
effect. After 8 weeks, the indicators of hyperlipidemia, liver injury,
and inflammation were measured. The treatment of P.
pentosaceus PP04 reduced the gain of total cholesterol
(TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C),
free fatty acids (FFAs), leptin, alanine aminotransferase (ALT), aspartate
aminotransferase (AST), lipopolysaccharides (LPS), and tumor necrosis
factor-α (TNF-α) significantly. The western blotting results
suggested P. pentosaceus PP04 ameliorated
high-fat diet-induced hyperlipidemia by the AMPK signaling pathway,
which stimulated lipolysis via upregulation of PPARα and inhibited
lipogenesis by downregulation of SREBP-1c, fatty acid synthase (FAS),
and stearoyl-CoA desaturase-1 (SCD1) mainly. Furthermore, P. pentosaceus PP04 improved high-fat diet-induced
oxidative stress effectively by triggering the Nrf2/CYP2E1 signaling
pathway that enhanced the antioxidant activity including superoxide
dismutase (SOD) and glutathione peroxidase (GSH-Px).
Many animal experiments and clinical trials showed that probiotics are effective for the treatment of alcoholic liver disease. Alcohol disrupts the composition of intestinal flora; probiotics modulate the gut microbiota and reverse alcohol-associated intestinal barrier dysfunction by decreasing intestinal mucosal permeability and preventing intestinal bacteria from translocating. Probiotics enhance immune responses and reduce the levels of alcohol-induced inflammatory cytokines and reactive oxygen species (ROS) production in the liver and intestine. Probiotics also increase fatty acid β-oxidation and reduce lipogenesis, combating alcohol-induced hepatic steatosis. In this review, we summarize the current knowledge regarding the mechanism of action of probiotics for reducing the effects of alcoholic liver disease.
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