266 research outputs found

    NFYA promotes the anti-tumor effects of gluconeogenesis in hepatocellular carcinoma through the regulation of PCK1 expression

    Get PDF
    Reprogramming of glucose metabolism occurs in many human tumor types, and one of these, gluconeogenesis, is known to exhibit anti-tumor effects in hepatocellular carcinoma (HCC). The transcription factor NFYA regulates gluconeogenesis in the normal liver tissue, but the function of the NFYA-gluconeogenesis axis in cancer and the functional differences of NFYA splicing variants in the regulation of gluconeogenesis is still unclear. Here, we demonstrate that NFYAv2, the short-form variant, upregulates the transcription of a gluconeogenic enzyme PCK1. We further reveal that its regulation induces high ROS levels and energy crisis in HCC and promotes cell death. These indicate that the NFYAv2-gluconeogenesis axis has enhanced anti-tumor effects in HCC, suggesting that the axis may be a potential therapeutic target for HCC. Furthermore, Nfyav1-deficient mice, spontaneously overexpressing Nfyav2, had no increasing gluconeogenesis in the liver. Taken together, our results reveal NFYAv2-gluconeogenesis axis has anti-tumor effects and the potential for NFYAv2 to be a safer therapeutic target for HCC

    Connective tissue mast cells store and release noradrenaline

    Get PDF
    Mast cells are present in mucosal and connective tissues throughout the body. They synthesize and release a wide variety of bioactive molecules, such as histamine, proteases, and cytokines. In this study, we found that a population of connective tissue mast cells (CTMCs) stores and releases noradrenaline, originating from sympathetic nerves. Noradrenaline-storing cells, not neuronal fibers, were predominantly identified in the connective tissues of the skin, mammary gland, gastrointestinal tract, bronchus, thymus, and pancreas in wild-type mice but were absent in mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice. In vitro studies using bone marrow-derived mast cells revealed that extracellular noradrenaline was taken up but not synthesized. Upon ionomycin stimulation, noradrenaline was released. Electron microscopy analyses further suggested that noradrenaline is stored in and released from the secretory granules of mast cells. Finally, we found that noradrenaline-storing CTMCs express organic cation transporter 3 (Oct3), which is also known as an extraneuronal monoamine transporter, SLC22A3. Our findings indicate that mast cells may play a role in regulating noradrenaline concentration by storing and releasing it in somatic tissues

    Effect of Ga content on luminescence and defects formation processes in Gd3(Ga,Al)5O12:Ce single crystals

    Get PDF
    The work was supported by the Institutional Research Funding IUT02-26 of the Estonian Ministry of Education and Research and the project 16-15569S of the Czech Science Foundation.Luminescence characteristics of Ce3+ - doped Gd3GaxAl5-xO12 single crystals with different Ga contents (x = 1, 2, 3, 4, 5) are studied in the 9–500 K temperature range. The spectra of the afterglow, photoluminescence, radioluminescence, and thermally stimulated luminescence (TSL) of each crystal coincide. The increase of the Ga content results in the high-energy shift of the spectra while the radioluminescence intensity at 9 K remains practically constant up to x = 4. No Ce3+ emission is observed in case of x = 5. The total TSL intensity drastically increases, reaches the maximum value around x = 2–3, and then decreases due to the thermal quenching of the Ce3+ emission. The TSL glow curve maxima are gradually shifting to lower temperatures, and the dependence of the maxima positions and the corresponding trap depths on the Ga content is close to linear. However, the activation energy of the TSL peaks creation under irradiation of the crystals in the 4f – 5d1 absorption band of Ce3+ decreases drastically with the increasing Ga content (especially in the range of x = 1–2), and this dependence is found to be strongly nonlinear. Possible reasons of the nonlinearity are discussed.Estonian Ministry of Education and Research IUT02-26; Czech Science Foundation 16-15569S; Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART

    High-throughput analysis of anthocyanins in horticultural crops using probe electrospray ionization tandem mass spectrometry (PESI/MS/MS)

    Get PDF
    農作物に含まれる成分を簡便・迅速に分析する技術を確立 --煩雑な抽出や分離操作が不要、わずか3分間で81種類のアントシアニンを分析可能--. 京都大学プレスリリース. 2023-03-30.Plant secondary metabolites exhibit various horticultural traits. Simple and rapid analysis methods for evaluating these metabolites are in demand in breeding and consumer markets dealing with horticultural crops. We applied probe electrospray ionization (PESI) to evaluate secondary metabolite levels in horticultural crops. PESI does not require pre-treatment and separation of samples, which makes it suitable for high-throughput analysis. In this study, we targeted anthocyanins, one of the primary pigments in horticultural crops. Eighty-one anthocyanins were detected in approximately 3 minutes in the selected reaction-monitoring mode. Tandem mass spectrometry (MS/MS) could adequately distinguish between the fragments of anthocyanins and flavonols. Probe sampling, an intuitive method of sticking a probe directly to the sample, could detect anthocyanins qualitatively on a micro-area scale, such as achenes and receptacles in strawberry fruit. Our results suggest that PESI/MS/MS can be a powerful tool to characterize the profile of anthocyanins and compare their content among cultivars

    Background contributions in the electron-tracking Compton camera onboard SMILE-2+

    Full text link
    The Mega electron volt (MeV) gamma-ray observation is a promising diagnostic tool for observing the universe. However, the sensitivity of MeV gamma-ray telescopes is limited due to peculiar backgrounds, restricting the application of MeV gamma rays for observation. Identification of backgrounds is crucial for designing next-generation telescopes. Therefore, herein, we assessed the background contribution in the electron-tracking Compton camera (ETCC) on board the SMILE- 2+ balloon experiment. This assessment was performed using the Monte Carlo simulation. The results revealed that the background below 400 keV existed due to the atmospheric gamma-ray background, the cosmic-ray/secondary-particle background, and the accidental background. On the other hand, the unresolved background component, which was not likely to be relevant to direct Compton-scattering events in the ETCC, was confirmed above 400 keV. Overall, this study demonstrated that the Compton-kinematics test provides a powerful tool to remove the background and principally improves the signal-to-noise ratio at 400 keV by an order of magnitude.Comment: 11 pages, 18 figure
    corecore