Anti-Albumin Antikörper (A29774)

Palmitic acid (PA)-induced vascular endothelial inflammation plays a pivotal role in the occurrence and development of vascular diseases. The present study was conducted to examine the effect of homoplantaginin, a main flavonoid from a traditional Chinese medicine Salvia plebeia R. Br., on PA-treated human umbilical vein endothelial cells inflammation and the underlying molecular mechanism. Firstly, we found that homoplantaginin (0.1, 1, 10 μM) dose-dependently reduced expression of toll-like receptor-4 evoked by PA (100 μM). The inhibitory effect of homoplantaginin was further confirmed under lipopolysaccharide challenge. In addition, downstream adapted proteins including myeloid differentiation primary response gene 88, toll/interleukin-1 receptor-domain containing adaptor-inducing interferon-β and tumor necrosis factors receptor associated factor-6 were successfully inhibited by homoplantaginin under PA treatment. Also, we found that homoplantaginin tightly controlled PA-induced reactive oxygen species to prevent nucleotide-binding domain-like receptor 3 (NLRP3) inflammasome activation by suppressing reactive oxygen species-sensitive thioredoxin-interacting protein, NLRP3, and caspase-1. Meanwhile, protein and mRNA levels of inflammatory mediators (interleukin-1β, intercellular cell adhesion molecule-1, and monocyte chemotactic protein-1) were decreased by homoplantaginin. Furthermore, homoplantaginin restored PA-impaired nitric oxide generation. Taken together, these results indicated that homoplantaginin protected endothelial cells from ameliorating PA-induced endothelial inflammation via suppressing toll-like receptor-4 and NLRP3 pathways, and restoring nitric oxide generation, suggesting it may be a potential candidate for further development in the prevention and treatment of vascular diseases.

Homo sapiens longevity assurance homolog 2 of yeast LAG (Lass2) catalyzes the synthesis of long-chain ceramide which is an essential element of membranous structures. Deletion of Lass2 is associated with a high risk of spontaneous or DEN-induced hepatocellular carcinoma (HCC), yet the mechanism remains unclear. In the present study, we found extensive vesicles in hepatocytes of one-month-old Lass2-knockout (KO) mice. Hepatic biochemical indices were increased and expression of albumin was attenuated in the one‑month Lass2-KO liver. The results indicate that the injuries of the hepatocytes in young Lass2-KO mice, based on the results of Gene Ontology analysis of mRNA microarray of Lass2-KO liver vs. wild-type liver showed 'wounding response' was the mostly possible altered pathway in the Lass2-KO mice. miR-mRNA integrated analysis revealed that miR-694 was downregulated while its target gene tumor necrosis factor α-induced protein 3 (Tnfaip3) was upregulated, as confirmed by qPCR. The expression of NF-κB which is negatively controlled by Tnfaip3 was detected by qPCR and was found to be downregulated. Herein, we first report that Lass2 deficiency caused the downregulation of miR-694 and the upregulation of its target gene Tnfaip3 in vivo in mice, which may be related to a high risk of occurrence of HCC.

BACKGROUND/AIMS:

We previously documented the presence of Telocytes (TCs) in liver and further indicated the potential roles of TCs in liver regeneration after hepatectomy. Pregnancy-induced liver growth, other than liver regeneration after hepatectomy, is a physiological hepatic adaption to meet the enhanced nutritional and metabolic demands. However, the possible roles of TCs in pregnancy-induced liver growth remain unknown.

METHODS:

Pregnant mice were sacrificed at different time points (pregnancy day 0.5, 4.5, 8.5, 10.5, 12.5, 14.5, 16.5, and 18.5). The liver weight was used to evaluate the liver growth during pregnancy. Hepatocytes proliferation was determined by albumin and 5-ethynyl-2'- deoxyuridine (EdU) double immunostaining while TCs were counted by double immunolabeling for CD34/PDGFR-α.

RESULTS:

Pregnancy-induced liver growth was preceded by increased proliferation of hepatocytes at pregnancy day 4.5, 8.5, 14.5 and 16.5. Furthermore, the number of TCs in liver detected by double immunolabeling for CD34/PDGFR-α was significantly increased at pregnancy day 4.5 and day 14.5, that was coincident with the occurrence of two peaks of hepatic cell proliferation during pregnancy.

CONCLUSION:

Our results suggest a possible relationship between TCs and hepatocyte proliferation in pregnancy-induced liver growth.