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Background Circulating levels of the systemic inflammation marker C-reactive protein (CRP) have been associated with increased risk and poor outcomes of many diseases, such as cardiovascular events and cancer. Accumulating evidence has indicated that the conformational rearrangement of human pentameric CRP (pCRP) to monomeric CRP (mCRP) is a prerequisite for participation in the pathogenesis. Therefore, determining the mechanism of the dissociation of pCRP into pro-inflammatory mCRP under physiological/pathological circumstances has been intriguing. Methods The effects of oxidative and acidic stress occurring in inflammation on pCRP were examined by electrophoresis, electron microscopy, protein fluorescence, neoepitope expression and endothelial cell responses. Results Reactive oxygen species (ROS) generated by the copper-hydrogen peroxide system could rapidly induce the dissociation of CRP at mild acidic pH within four hours, but not at physiological pH of 7.4. Meanwhile, mannitol, a ROS scavenger, could not protect against dissociation, which implied that local ROS from accessible histidine residues may be crucially beneficial to the formation of mCRP in a redox-balanced microenvironment. Furthermore, mCRP generated by ROS could be reduced by DTT, which indicated the exposure of functional motif aa35-47, and showed potent proinflammatory actions on endothelial cells, comparable to mCRP generated by urea. Conclusion dissociation of pCRP to mCRP could be rapidly induced by ROS from copper- hydrogen peroxide system in dependence on mildly acidic stress regardless of a redox-balanced microenvironment.

To investigate how Chaiyuwendan decoction (CWD) affects endocannabinoid levels in the adipose tissue of depressed rats.Twenty-four male Sprague-Dawley rats were randomly divided into four groups with six rats in each. One group was randomly selected as the control group. The remaining three groups were subjected to chronic stress to induce depression. Groups were randomly assigned as a model group, CWD group, and amitriptyline group. CWD was given to the CWD group once a day from the second day of modeling. The amitriptyline group was administered amitriptyline intragastrically (10 mg/kg) once a day. After treatment for 21 days, body weight and fat weight were measured and the levels of N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), and N-palmitoylethanolamine (PEA) in adipose tissue were determined with liquid chromatography-mass spectrometry.Compared with the control group, body weight, fat weight, AEA, and PEA were significantly lower, and 2-AG was higher, in the model group (P0.05, P0.01). Compared with the model group, body weight, fat weight, the AEA, and PEA levels were significantly higher, and 2-AG level was significantly lower in the CWD group (P0.05). However, the levels did not differ significantly between the CWD group and the amitriptyline group.CWD could regulate the levels of AEA, 2-AG, and PEA in rats with depression induced by chronic stress.

Objective To investigate the effects of Zhi Zi (Fructus Gardeniae) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet in the rat. Methods A rat model of NAFLD was established using a high-fat diet. Twenty one rats were randomly divided into a normal group, a model group and a Zhi Zi treatment group, 7 rats per group. Drinking water and the drug were intragastrically administrated for 5 weeks. Samples were then taken to observe pathological changes of the liver tissue (HE staining); changes in the fat metabolism pathway e. g. triglyceride (TG) and free fatty acid (FFA) content; alterations in liver function, i.e. serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity; and differences in tumor necrosis factor α (TNF-α) and P-lkB protein expression in the liver tissue. Results Fatty degeneration and vacuole-like changes of different degrees occurred in hepatic cells of the model group. Markers for fat metabolism, serum ALT and AST activities, and expression of TNF-α and P-lkB proteins in liver tissue significantly increased. Fat metabolism in the Zhi Zi group significantly reduced, as shown by a drop in marker levels. Serum ALT and AST activities, and expression of TNF-α, P-lkB proteins in liver tissue were also significantly decreased in this group. Conclusion Zhi Zi has a very strong inhibitory action on lipidosis and inflammatory injury in the rat model of NAFLD. This mechanism may possibly be related to the inhibition of the free fatty acid metabolism pathway.

Objective To investigate the expression of insulin-like growth factor binding protein-3 (IGFBP-3) in penile cavernous of streptozotocin (STZ)-induced DM rats and whether downregulation of IGFBP-3 by intracavernosal injection of short hairpin ribonucleic acid (shRNA) targeting IGFBP-3 could improve the erectile function in DM rats. Materials and Methods Diabetes was induced in rats by intraperitoneal injection of STZ, and the expression of IGFBP-3 in the penile tissue of adult normal and DM male rats was assayed using reverse transcriptase-polymerase chain reaction and Western blot. Next, shRNA-targeting IGFBP-3 and a scramble sequence were injected into the penile corpora cavernosa of DM rats. At 12 weeks after shRNA-IGFBP-3 administration, the intracavernous pressure in response to electrical stimulation of the cavernous nerves was evaluated. The expression of IGFBP-3 was assayed by Western blot. The concentration of cyclic guanosine monophosphate in the corpus cavernosum was assayed by enzyme-linked immunosorbent assay. Results At 12 week after intraperitoneal administration of STZ, IGFBP-3 expression had increased in the penis of the DM rat (P