SSAO inhibitors suppress hepatocellular tumor growth in mice.

Vascular adhesion protein-1 (VAP-1) is both an endothelial adhesion molecule involved in leukocytes emigration, and an oxidase belonging to the family of semicarbazide-sensitive amine oxidases (SSAOs). The enzyme activity of VAP-1 plays an important role in the migration of myeloid-derived suppressor cells (MDSCs) into tumor site, and SSAO inhibitors can block the function of VAP-1. The effects of SSAO inhibitors on leukocyte infiltration and tumor progression were evaluated in H22 hepatocellular carcinoma-bearing C57BL/6 mice. Tumor weight and volume were measured after SSAO inhibitor treatment. Then, MDSCs recruitment and neo-angiogenesis were determined using immunostaining. SSAO inhibitors significantly blocked the catalytic activity of VAP-1 in tumor, attenuated tumor progression, and reduced neo-angiogenesis. CD11b(+) and Gr-1(+) MDSCs, which normally infiltrate into tumors, were significantly diminished in tumor-bearing mice treated with SSAO inhibitors. The present study demonstrated that SSAO inhibitors might have an anti-tumor effect on hepatocellular carcinoma by inhibiting recruitment of CD11b(+) and Gr-1(+) cells and hindering angiogenesis, which could be attributed to impairing the catalytic activity of VAP-1.

Investigation of the Performance of Heterogeneous MOF-Silver Nanocube Nanocomposites as CO2 Reduction Photocatalysts by In Situ Raman Spectroscopy.

Here, we fabricated two different heterogeneous nanocomposites, core-shell MOF-AgNC and corner MOF-AgNC, as photocatalysts for CO2 conversion by generating metal-organic frameworks (MOFs) on silver nanocube templates. These MOF-AgNC nanocomposites showed good CO2 adsorption features and high CO2 reduction reactivity. The performances of these MOF-AgNC nanocomposites in CO2 adsorption and CO2 reduction reactions can be characterized by in situ Raman spectrum measurement. The corner MOF-AgNC nanocomposite exhibited a faster CO2 adsorption rate than the core-shell MOF-AgNC nanocomposite, which was due to the higher surface area/volume ratio of the MOF in corner MOF-AgNC. The CO2 reaction reactivity and mechanisms (products of the reaction) of CO2 reduction also depended on the morphologies of MOF-AgNC nanocomposites, which were caused by different reaction environments at the interface between the MOF and AgNCs. The CO2 reduction reactivity of MOF-AgNC nanocomposites also exhibited high sensitivity to the irradiation intensity and wavelength, which was caused by the variation of the number of hot electrons and their positions in AgNCs with the irradiation intensity and irradiation wavelength, respectively. This method for the synthesis of heterogeneous nanocomposites should make it possible to design photocatalysts for various reactions by carefully designing the morphology and composition of nanocomposites.

CACYBP Enhances Cytoplasmic Retention of P27Kip1 to Promote Hepatocellular Carcinoma Progression in the Absence of RNF41 Mediated Degradation.

Calcyclin-binding protein (CACYBP) is a multi-ligand protein implicated in the progression of various human cancers. However, its function in hepatocellular carcinoma (HCC) remains unknown. Methods: The expression of CACYBP and RNF41 (RING finger protein 41) in HCC cancer and adjacent non-tumor tissues was detected by immunohistochemistry. CCK-8 assays, colony formation assays, flow cytometry detection and xenograft models were used to evaluate the impact of CACYBP expression on HCC cell growth, apoptosis and cell cycle regulation. Immunoprecipitation and ubiquitination assays were performed to determine how RNF41 regulates CACYBP. The regulatory mechanism of RNF41-CACYBP signaling axis on P27Kip1 was investigated by western blotting and immunofluorescence. Results: CACYBP was highly expressed and associated with poor prognosis in HCC. CACYBP expression was required for HCC cell growth in vitro and in vivo. Moreover, we identified RNF41 as a specific binding partner of CACYBP at exogenous and endogenous levels. RNF41 recruited CACYBP by its C-terminal substrate binding domain, subsequently ubiquitinating CACYBP and promoting its degradation in both proteasome- and lysosome-dependent pathways. In HCC tissues, RNF41 expression was reduced and conferred a negative correlation with CACYBP expression. Mechanistically, CACYBP overexpression stimulated the Ser10, Thr157 and Thr198 phosphorylation of P27Kip1 and its cytoplasmic retention, and RNF41 co-expression attenuated this phenomenon. CACYBP depletion led to decreased levels of cyclin D1, cyclin A2, CDK2 and CDK4, causing a typical cell cycle arrest at G1/S phase and increasing apoptosis in HCC cells. P27Kip1-S10D but not P27Kip1-S10A reconstitution rescued partially the cell cycle function and apoptotic feature after CACYBP depletion. Conclusion: Our findings provide novel insights into the functional role and regulatory mechanism of CACYBP in HCC.

Complete mitochondrial DNA genome of Triplophysa venusta (Cypriniformes: Cobitida).

The complete mitochondrial DNA sequence of Triplophysa venusta was determined using a PCR-based method in our present study. The genome is totally 16 574 bp in length and contains 13 protein-coding genes, 2 ribosomal RNA, 22 transfer RNA genes, and 1 non-coding control region. The overall base composition of T. venusta is A 27.8%, T 26.9%, C 26.9%, and G 18.4%, with an A + T bias of 54.7%. This complete mitogenome of T. venusta provides a basic data for studies on species identification, molecular systematics, and conservation genetics. The phylogenetic trees consistently showed that the Family Cobitidae was divided into three major clades: the subfamily Botiidae, the subfamily Nemaeheilidae, and the subfamily Cobitinae. Cobitinae and Nomaeheilidae formed a main Loach clade, with Botiidae clustered at the basal.