PKC delta (Phospho-Ser645) ELISA Kit

Bisphenol F (BPF) and bisphenol S (BPS) have been widely used as alternatives to bisphenol A (BPA). With their increasing use, BPF and BPS have also been released into the environment; thus, their potential risks to aquatic organisms and humans are drawing attention. The objective of this study was to identify the interactions between key pathways and hub genes in zebrafish following BPF and BPS exposure, and to evaluate the potential risks to human health. We identified three key pathways using KEGG over-representation test and Gene Set Enrichment Analysis (GSEA): 'Necroptosis,'Adipocytokine signaling pathway,' and 'C-type lectin receptor signaling pathway.' Moreover, three hub genes (mstlra, prkcdb, and pik3cb) and detailed interactions among the pathways were examined by the analyses of PPI network, subcellular location, and shortest-pathway. Surprisingly, all three pathways were strongly associated with a potential risk of cancer, as reported previously. In addition, the results of KOBAS shown in 'Pathways in Cancer' and 'Cancers' belong to the top 10 terms in pathway enrichment analyses using genes related to BPF or BPS in human, as was found using GenCLiP. Moreover, the Kaplan-Meier survival analysis was performed using homologenes (MST1R, PIK3CB and PRKCD) of hub genes in human to evaluate whether exposure to bisphenols may adversely affect breast cancer. Taken together, these studies demonstrate the potential carcinogenicity of BPF and BPS. To our knowledge, this is the first study on three overlapping key pathways and three hub genes to investigate BPF and BPS exposure-related mechanisms and subsequent interactions in zebrafish. (C) 2018 Published by Elsevier Ltd.

Inv(11)(p15q23), found in myelodysplastic syndromes and acute myeloid leukemia, leads to expression of a fusion protein consisting of the N-terminal of nucleoporin 98 (NUP98) and the majority of the lysine methyltransferase 2A (KMT2A). To explore the transforming potential of this fusion we established inducible iNUP98-KMT2A transgenic mice. After a median latency of 80 weeks, over 90% of these mice developed signs of disease, with anemia and reduced bone marrow cellularity, increased white blood cell numbers, extramedullary hematopoiesis, and multilineage dysplasia. Additionally, induction of iNUP98-KMT2A led to elevated lineage marker-negative Sca-1(+) c-Kit(+) cell numbers in the bone marrow, which outcompeted wildtype cells in repopulation assays. Six iNUP98-KMT2A mice developed transplantable acute myeloid leukemia with leukemic blasts infiltrating multiple organs. Notably, as reported for patients, iNUP98-KMT2A leukemic blasts did not express increased levels of the HoxA-B-C gene cluster, and in contrast to KMT2A-AF9 leukemic cells, the cells were resistant to pharmacological targeting of menin and BET family proteins by MI-2-2 or JQ1, respectively. Expression of iNUP98-KMT2A in mouse embryonic fibroblasts led to an accumulation of cells in G1 phase, and abrogated replicative senescence. In bone marrow-derived hematopoietic progenitors, iNUP98-KMT2A expression similarly resulted in increased cell numbers in the G1 phase of the cell cycle, with aberrant gene expression of Sirt1, Tert, Rbl2, Twist1, Vim, and Prkcd, mimicking that seen in mouse embryonic fibroblasts. In summary, we demonstrate that iNUP98-KMT2A has in vivo transforming activity and interferes with cell cycle progression rather than primarily blocking differentiation.