Tumor promoter TPA activates Wnt/β-catenin signaling in a casein kinase 1-dependent manner.

The tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) has been defined by its ability to promote tumorigenesis on carcinogen-initiated mouse skin. Activation of Wnt/β-catenin signaling has a decisive role in mouse skin carcinogenesis, but it remains unclear how TPA activates Wnt/β-catenin signaling in mouse skin carcinogenesis. Here, we found that TPA could enhance Wnt/β-catenin signaling in a casein kinase 1 (CK1) ε/δ-dependent manner. TPA stabilized CK1ε and enhanced its kinase activity. TPA further induced the phosphorylation of LRP6 at Thr1479 and Ser1490 and the formation of a CK1ε-LRP6-axin1 complex, leading to an increase in cytosolic β-catenin. Moreover, TPA increased the association of β-catenin with TCF4E in a CK1ε/δ-dependent way, resulting in the activation of Wnt target genes. Consistently, treatment with a selective CK1ε/δ inhibitor SR3029 suppressed TPA-induced skin tumor formation in vivo, probably through blocking Wnt/β-catenin signaling. Taken together, our study has identified a pathway by which TPA activates Wnt/β-catenin signaling

Energy Transfer From Fluorescent Proteins To Metal Nanoparticles

Energy transfer plays a significant role in numerous chemical, physical, and biological processes. While the use of fluorescent proteins in Forster resonance energy transfer (FRET) studies of biomolecules is common, energy transfer between fluorescent proteins and inorganic nanoparticles has not been explored in detail. In this study, energy transfer from fluorescent phycobiliproteins to noble metal nanoparticles was analyzed. Solutions of B-phycoerythrin (B-PE) were mixed with colloidal Au and Ag nanoparticles and were characterized by steady-state and time-resolved fluorescence spectroscopy to determine the magnitude and mechanism of the energy transfer. It was found that the protein fluorescence was quenched after the addition of metal nanoparticles. Electron microscopy and absorption spectroscopy confirmed that B-PE was adsorbed onto the nanoparticles, creating a favorable geometry for quenching. Time-resolved fluorescence spectroscopy showed that B-PE fluorescence lifetimes decreased from 2.2 ns to 0.5 and 0.6 ns upon adsorption onto Au and Ag nanoparticles, respectively, corresponding to energy transfer efficiencies of \u3e70%. Our results, which include lifetimes, efficiencies, and energy transfer distances, show that energy was transferred via the surface energy transfer (SET) mechanism, rather than FRET

Levetiracetam versus phenytoin for the treatment of established status epilepticus: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To compare the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus. METHODS: In this systematic review, we searched Medline, Embase, and Cochrane databases from their inception with no language restrictions until May 8, 2019 and updated on February 5, 2020, for randomized controlled trials comparing the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus. A Meta-analysis was conducted to calculate the risk ratio (RR) using random-effects models. RESULTS: We identified 7 trials with a total of 1028 participants. Levetiracetam was not associated with an increased rate of clinical seizure cessation within 60 min compared with phenytoin (RR, 1.02; 95 %CI, 0.92-1.13; I2 = 3%; 60.0 % [309/515] vs 59.3 % [275/463];12 more events [95 % CI, -48 to 77] per 1000 participants; moderate-quality evidence). Results were similar in the subgroup analysis of adults and children. The sample size met the optimum size in trial sequential analysis. There were also no statistically significant effects on good functional outcome (RR, 1.05; 95 % CI, 0.90-1.23), admission to critical care (RR, 1.09; 95 % CI, 0.95-1.24), or all-cause mortality (RR, 1.09; 95 % CI, 0.55-2.16). CONCLUSIONS: Moderate-quality evidence suggested that levetiracetam was not significantly superior to phenytoin in seizure cessation in patients with established status epilepticus

Experimental study on friction pressure drop and circumferential heat transfer characteristics in helical tubes

Helical tubes are widely used in nuclear plants, heat recovery process, and refrigeration technology. The fluid is influenced by centrifugal force flow through the helical tube, accompanied by secondary flow which is conducive to the enhancement of heat transfer. However, the uneven circumferential heat transfer caused by the secondary flow was seldom reported, while the pressure drops and heat transfer characteristics of helical tubes under single-phase and two-phase flow conditions need to be supplemented. This paper investigated the friction pressure drop and circumferential heat transfer characteristics based on the experiments on helical tubes with the coil diameter to the tube diameter varying from 28.5 to 128.5 and lift angle varying from 3° to 10°. The results showed that the coil diameter was the key parameter affecting the pressure drop and non-uniform circumferential heat transfer, compared with the lift angle. At the same cross section, the heat transfer coefficient at the outside tube wall was the highest, which was more obvious under small coil diameter conditions. Correlations of flow resistance and heat transfer were proposed for the single-phase and saturated boiling two-phase flow, respectively, and the predicted values were improved compared with the prediction results of correlations in the existing literature

Ethacrynic Acid Exhibits Selective Toxicity to Chronic Lymphocytic Leukemia Cells by Inhibition of the Wnt/β-Catenin Pathway

Aberrant activation of Wnt/β-catenin signaling promotes the development of several cancers. It has been demonstrated that the Wnt signaling pathway is activated in chronic lymphocytic leukemia (CLL) cells, and that uncontrolled Wnt/β-catenin signaling may contribute to the defect in apoptosis that characterizes this malignancy. Thus, the Wnt signaling pathway is an attractive candidate for developing targeted therapies for CLL. assays further confirmed the inhibitory effect of EA on Wnt/β-catenin signaling. Cell viability assays showed that EA selectively induced cell death in primary CLL cells. Exposure of CLL cells to EA decreased the expression of Wnt/β-catenin target genes, including LEF-1, cyclin D1 and fibronectin. Immune co-precipitation experiments demonstrated that EA could directly bind to LEF-1 protein and destabilize the LEF-1/β-catenin complex. N-acetyl-L-cysteine (NAC), which can react with the α, β-unsaturated ketone in EA, but not other anti-oxidants, prevented the drug's inhibition of Wnt/β-catenin activation and its ability to induce apoptosis in CLL cells.Our studies indicate that EA selectively suppresses CLL survival due to inhibition of Wnt/β-catenin signaling. Antagonizing Wnt signaling in CLL with EA or related drugs may represent an effective treatment of this disease