The role of hepatic Surf4 in lipoprotein metabolism and the development of atherosclerosis in apoE-/- mice.

Elevated plasma levels of low-density lipoprotein-C (LDL-C) increase the risk of atherosclerotic cardiovascular disease. Circulating LDL is derived from very low-density lipoprotein (VLDL) metabolism and cleared by LDL receptor (LDLR). We have previously demonstrated that cargo receptor Surfeit 4 (Surf4) mediates VLDL secretion. Inhibition of hepatic Surf4 impairs VLDL secretion, significantly reduces plasma LDL-C levels, and markedly mitigates the development of atherosclerosis in LDLR knockout (Ldlr-/-) mice. Here, we investigated the role of Surf4 in lipoprotein metabolism and the development of atherosclerosis in another commonly used mouse model of atherosclerosis, apolipoprotein E knockout (apoE-/-) mice. Adeno-associated viral shRNA was used to silence Surf4 expression mainly in the liver of apoE-/- mice. In apoE-/- mice fed a regular chow diet, knockdown of Surf4 expression significantly reduced triglyceride secretion and plasma levels of non-HDL cholesterol and triglycerides without causing hepatic lipid accumulation or liver damage. When Surf4 was knocked down in apoE-/- mice fed the Western-type diet, we observed a significant reduction in plasma levels of non-HDL cholesterol, but not triglycerides. Knockdown of Surf4 did not increase hepatic cholesterol and triglyceride levels or cause liver damage, but significantly diminished atherosclerosis lesions. Therefore, our findings indicate the potential of hepatic Surf4 inhibition as a novel therapeutic strategy to reduce the risk of atherosclerotic cardiovascular disease.

Systemic effects of ingested Lactobacillus rhamnosus: inhibition of mast cell membrane potassium (IKCa) current and degranulation.

Exposure of the intestine to certain strains lactobacillus can have systemic immune effects that include the attenuation of allergic responses. Despite the central role of mast cells in allergic disease little is known about the effect of lactobacilli on the function of these cells. To address this we assessed changes in rat mast cell activation following oral treatment with a strain of Lactobacillus known to attenuate allergic responses in animal models. Sprague Dawley rats were fed with L. rhamnosus JB-1 (1×10(9)) or vehicle control for 9 days. Mediator release from peritoneal mast cells (RPMC) was determined in response to a range of stimuli. Passive cutaneous anaphylaxis (PCA) was used to assess mast cell responses in vivo. The Ca(2+) activated K(+) channel (KCa3.1) current, identified as critical to mast cell degranulation, was monitored by whole cell patch-clamp. L. rhamnosus JB-1 treatment lead to significant inhibition of mast cell mediator release in response to a range of stimuli including IgE mediated activation. Furthermore, the PCA response was significantly reduced in treated rats. Patch-clamp studies revealed that RPMC from treated animals were much less responsive to the KCa3.1 opener, DCEBIO. These studies demonstrate that Ingestion of L. rhamnosus JB-1 leads to mast cell stabilization in rats and identify KCa3.1 as an immunomodulatory target for certain lactobacilli. Thus the systemic effects of certain candidate probiotics may include mast cell stabilization and such actions could contribute to the beneficial effect of these organisms in allergic and other inflammatory disorders.

[Advance in study on active protein and peptide produced by marine bacteria--a review].

Biological active resources are various and abundant in the ocean. With this realization, active proteins and peptides especially marine bacteria active proteins and peptides have attracted much attention recently. The achievements in the study of bioactivities of marine bacterial proteins and peptides were reviewed in this paper. Acquisition and potential applications of these marine bacteria active products were then proposed. Additionally, we focused on the prospective outline on the study of this field.

[Isolation and purification of ribosome-inactivating proteins from bitter melon seeds by ion exchange chromatographic columns in series].

An anion exchange chromatographic column (DEAE-650C) and a cation exchange chromatographic column (CM-650C) were connected in series on a perfusion chromatography workstation. The crude extract of bitter melon seeds flowed through the two columns and the unadsorbed fraction on the DEAE-650C column was then directly readsorbed on the CM-650C column. Two protein components with antifungal activity were eluted from the cation exchange chromatographic column by linear salt gradient. Both of them were found to be homogeneous by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and their relative molecular masses were estimated to be about 30 000. Their N-terminal amino acid sequences are DVSFRLSGADPRSYGMFI and DVNFDLSTATAK. All of the above suggested that they are alpha-momorcharin (alpha-MMC) and beta-momorcharin (beta-MMC), respectively, two type I ribosome-inactivating proteins (Rips) of bitter melon seeds. a-MMC shows antifungal activity against Fusarium oxysporum and Pythium aphanidermatum, while beta-MMC shows antifungal activity against Pythium aphanidermatum. But they are not against Sclerotium rolfsii. In the study, quantitative recoveries of alpha-MMC and beta-MMC were 13.8% and 8.0%, respectively, from decorticated seeds by ion exchange chromatographic columns in series.