N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth.

Despite the evidences of elevated expression of Mer tyrosine kinase (MerTK) in multiple human cancers, mechanisms underlying the oncogenic roles of MerTK in hepatocellular carcinoma (HCC) remains undefined. We explored the functional effects of MerTK and N-Glycosylated MerTK on HCC cell survival and tumor growth. Here, we show that MerTK ablation increases reactive oxygen species (ROS) production and promotes the switching from glycolytic metabolism to oxidative phosphorylation in HCC cells, thus suppressing HCC cell proliferation and tumor growth. MerTK is N-glycosylated in HCC cells at asparagine 294 and 454 that stabilizes MerTK to promote oncogenic transformation. Moreover, we observed that nuclear located non-glycosylated MerTK is indispensable for survival of HCC cells under stress. Pathologically, tissue microarray (TMA) data indicate that MerTK is a pivotal prognostic factor for HCC. Our data strongly support the roles of MerTK N-glycosylation in HCC tumorigenesis and suggesting N-glycosylation inhibition as a potential HCC therapeutic strategy.

[Analyses on distribution and structure of blaCARB-2 in Klebsiella pneumoniae].

In order to characterize the structure of the beta-lactamase gene and its corresponding mobile genetic elements in Klebsiella pneumoniae, the beta-lactamase genes from 240 clinical Klebsiella pneumoniae isolates were studied. blaCARB-2, a newly characterized gene, was extensively investigated utilizing next-generation sequencing, PCR, molecular cloning, conjugation, and comparative genomics analysis. We identified 11 beta-lactamase genes among the 240 clinical Klebsiella pneumoniae isolates; the blaCARB-2 gene exists only in one specific isolate (Klebsiella pneumoniae KP1276) (1/240, 0.42%). The blaCARB-2 gene lies on a conjugative plasmid pKP1276-82, a 182,450-bp plasmid, which encodes 222 open reading frames. The plasmid has seven resistance genes, termed blaCARB-2, blaKLUC, aadA1, aadA2, cmlA1, dfrA1, and sul2. Among these genes, blaCARB-2 was identified for the first time in Klebsiella pneumoniae. Four of these resistance genes and an int gene form a class 1 integron (int-blaCARB-2-aadA2-cmlA1-aadA1). Further studies show that the blaCARB-2, aadA2, and cmlA1 genes are resistant to their corresponding antibiotics and the blaCARB-2 exhibits higher resistance activities to penicillin beta-lactams. These results reveal the possibility of horizontal transfer of the resistance genes and dissemination of resistance among bacteria of different genera or species of Enterobacteriaceae.

[The effects of Shadu Cao Mixture on immune functions of immunosuppression mice].

OBJECTIVE: To investigate the effects of Shadu Cao Mixture (SDCM, traditional Chinese medicine) on immune functions of immunosuppression mice. METHODS: Fifty BALB/C mice were randomly divided into blank control group, model group, SDCM low-dose, middle-dose and high-dose group. Except the blank control group, other groups were intraperitoneal injected with cyclophosphamide (40 mg/kg) to establish immunosuppression mice model. The blank control group and model group received gavage administration with nonnal saline, while the other groups received gavage administration with different doses of SDCM (10, 20, 40 m/kg for 15 days) respectively. The number of leukocytes and serum levels of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in peripheral blood, spleen index, and the function of NK cells were measured. RESULTS: Compared with the model group , SDCM increased the number of leukocytes and serum concentrations of IL-2, TNF-α and IFN-γ in peripheral blood and improved the spleen index and the function of NK cells significantly (P < 0.05-0.01). CONCLUSION: SDCM could remarkably enhance the immune functions of immunosuppression mice induced by cyclophosphamide.