Apolipoprotein A-I Binding Protein Inhibits the Formation of Infantile Hemangioma through Cholesterol-Regulated Hypoxia-Inducible Factor 1α Activation.

Infantile hemangioma (IH) is the most frequent vascular tumor of infancy with unclear pathogenesis; disordered angiogenesis is considered to be involved in its formation. Apolipoprotein A-I binding protein (AIBP)-also known as NAXE (NAD [P]HX epimerase)-a regulator of cholesterol metabolism, plays a critical role in the pathological angiogenesis of mammals. In this study, we found that AIBP had much lower expression levels in both tissues from patients with IH and hemangioma endothelial cells (HemECs) than in adjacent normal tissues and human dermal vascular endothelial cells, respectively. Knockout of NAXE by CRISPR-Cas9 in HemECs enhanced tube formation and migration, and NAXE overexpression impaired tube formation and migration of HemECs. Interestingly, AIBP suppressed the proliferation of HemECs in hypoxia. We then found that reduced expression of AIBP correlated with increased hypoxia-inducible factor 1α levels in tissues from patients with IH and HemECs. Further mechanistic investigation demonstrated that AIBP disrupted hypoxia-inducible factor 1α signaling through cholesterol metabolism under hypoxia. Notably, AIBP significantly inhibited the development of IH in immunodeficient mice. Furthermore, using the validated mouse endothelial cell (ie, EOMA cells) and Naxe-/- mouse models, we demonstrated that both endogenous AIBP from tumors and AIBP in the tumor microenvironment limit the formation of hemangioma. These findings suggested that AIBP was a player in the pathogenesis of IH and could be a potential pharmacological target for treating IH.

Inhibition of BETs prevents heat shock-induced cell death via upregulating HSPs in SV40 large T antigen transfected cells.

BACKGROUND: Heat shock response is a protected mechanism against environmental changes for the organism, which must be tightly regulated. Bromodomain and extra terminal-containing protein family (BETs) regulate numerous gene expression in many physiological and pathological conditions, including viral infection. SV40 is considered as a highly human disease-associated virus. OBJECTIVE: We aimed to explore whether BETs play a role in heat shock in SV40 large T antigen transfected cells. METHODS: SV40LTA was transfected in HeLa cells using the Lipofectamine 8000. BETs inhibitor JQ1 and I-BET-762 was employed to treat transfected cells and HEK-293 T cells. Heat shock treatment was performed to determine the effect of JQ1 and I-BET-762 on these cells. Western blot and quantitative RT-PCR were carried out to assess the expression of HSP70 and other HSPs. RESULTS: We found that inhibition of BETs by JQ1 and I-BET-762 protects cells from heat shock-induced death in HEK293T cells. Both JQ1 and I-BET-762 induce the expression of HSPs and HSF1 in HEK-293 T cells. However, neither JQ1 nor I-BET-762 fail to induce the expression of HSPs in either HeLa or HBL-1 cells. When SV40 large T antigen was transfected into HeLa cells, the induction of HSP70 expressing and the protection of heat shock-induced cell death are reproduced by JQ1 and IBET treatment in these transfected cells. CONCLUSIONS: Inhibition of BETs by JQ1 and I-BET-762 prevents heat shock-induced cell death via upregulating HSPs in SV40 large T antigen transfected cells. Our data indicate a novel function of BETs in SV40 large T antigen transformed cells, affecting HSPs and HSF1 as well as its function on heat shock response.

Global 3'UTR shortening and down-regulation of repeated element related piRNA play crucial roles in boys with cryptorchidism.

BACKGROUND: Cryptorchidism is the most common congenital defect in children's genitourinary system. Decades of research have identified both environmental and genetic factors contribute to the etiology. METHODS: Small-RNA/mRNA-seq were performed on testicular tissues from cryptorchidism patients. Downstream analysis included mRNA expression, piRNA expression and miRNA expression. RESULTS: We find a global downregulation of repeated element related piRNA expression as well as a global 3'UTR shortening of mRNAs in patients with cryptorchidism. We also find that genes with shortened 3'UTR which are highly enriched in vascular endothelial growth and protein ubiquitination, tend to be up-regulated in cryptorchidism. These results indicate that boys with cryptorchidism may not have normal piRNA functions to protect developmental tissues from transposon invasion. Dysregulated shortened 3'UTR genes may affect normal testicular tissue development. CONCLUSION: In summary, our findings also provided the first landscape of gene regulation in cryptorchidism, especially in terms of post-transcriptional regulations.

Construction of Cu-Ce/graphene catalysts via a one-step hydrothermal method and their excellent CO catalytic oxidation performance.

Cu-Ce/graphene catalysts show high dispersion of metal particles and excellent activity and stability for catalytic oxidation. In this study, a hydrothermal method was used to synthesize a series of bimetallic Cu-Ce/graphene catalysts, and the effects of the proportions of Cu and Ce on CO oxidation were investigated in detail. Indispensable characterizations such as XPS, XRD, TEM, BET, and H2-TPR were conducted to explore the effect of the Cu/Ce molar ratio and the metal valence on the activity and determine the structure-performance relationship. The results showed that bimetallic supported catalysts, such as 3Cu5Ce/graphene, 1Cu1Ce/graphene, and 5Cu3Ce/graphene, possessed significant catalytic activity. Especially, the 5Cu3Ce/graphene catalyst showed highest catalytic activity for CO oxidation, the T 100 value was 132 °C, and the apparent activation energy was 68.03 kJ mol-1. Furthermore, the stability of the 5Cu3Ce/graphene catalyst was outstanding, which could be maintained for at least 12 h. Moreover, the CeO2 particles were well crystalline with the size 5-9 nm in these catalysts, and the CuO nanoparticles were well dispersed on CeO2 and graphene. Notably, the ratio of Cu/Ce in the catalyst was higher, the interaction between the Ce species and the graphene was stronger, and the Cu species were more easily reduced; this was beneficial for the oxidation of CO.