1,721,159 research outputs found

    La Completa inibizione della via di segnale mTORC1 è necessaria per la soppressione dell’epatocancerogenesi indotta dall’iperespressione dei protooncogeni AKT e N-Ras nel topo

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    Aim:Concomitant expression of activated forms of AKT and Ras protooncogenes in the mouse liver leads to rapid tumor development via strong activity of the mTORC1 pathway. In mouse hepatocytes, mTORC1 functions by regulating the p70S6K/RPS6 and 4E-BP1/eIF4E cascades. We investigated the effect of mTORC1 inhibition on hepatocarcinogenesis driven by AKT and Ras co-expression.Methods:Activated forms of AKT and Ras genes were injected together withRaptorfl/fl(conditional knockout) and Cre recombinase via hydrodynamic injection in mice to allow the expression of AKT and Ras in mTORC1 deleted hepatocytes. AKT/Ras mice were treated with Rapamycin, which inhibits p-RPS6 without affecting p-4E-BP1, for 7 weeks (starting immediately after hydrodynamic injection). 4E-BP1A4, an unphophorylable mutant of 4E-BP1, was co-injected with AKT and Ras into the mouse liver.Results:Disruption of mTORC1 byRaptorablation completely inhibited AKT/Ras induced hepatocarcinogenesisin vivo. Blocking of RPS6 pathway via Rapamycin effectively inhibited AKT/Ras induced hepatocarcinogenesis. Liver tissues from Rapamycin treated mice showed small clusters of lipid-rich preneoplastic cells with few proliferating cells. Inhibition of 4E-BP1/eIF4E cascade by injection of 4E-BP1A4 significantly delayed AKT/Ras induced liver tumor progression. However, over long term, large liver tumors eventually developed in AKT/Ras/4EBP1A4 mice. Combined treatment with Rapamycin and 4E-BP1A4 completely suppressed AKT/Ras hepatocarcinogenesis.Conclusion:Complete inhibition of mTORC1 is required to suppress liver cancer development induced by AKT and Ras protooncogenes in mice. The two major downstream effectors of mTORC1, RPS6 and 4E-BP1/eIF4E, are both required for AKT/Ras-driven hepatocarcinogenesis

    Electrochemical Determination of the “Furanic Index” in Honey

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    5-(hydroxymethyl)furan-2-carbaldehyde, better known as hydroxymethylfurfural (HMF), is a well-known freshness parameter of honey: although mostly absent in fresh samples, its concentration tends to increase naturally with aging. However, high quantities of HMF are also found in fresh but adulterated samples or honey subjected to thermal or photochemical stresses. In addition, HMF deserves further consideration due to its potential toxic effects on human health. The processes at the origin of HMF formation in honey and in other foods, containing saccharides and proteins—mainly non-enzymatic browning reactions—can also produce other furanic compounds. Among others, 2-furaldehyde (2F) and 2-furoic acid (2FA) are the most abundant in honey, but also their isomers (i.e., 3-furaldehyde, 3F, and 3-furoic acid, 3FA) have been found in it, although in small quantities. A preliminary characterization of HMF, 2F, 2FA, 3F, and 3FA by cyclic voltammetry (CV) led to hypothesizing the possibility of a comprehensive quantitative determination of all these compounds using a simple and accurate square wave voltammetry (SWV) method. Therefore, a new parameter able to provide indications on quality of honey, named “Furanic Index” (FI), was proposed in this contribution, which is based on the simultaneous reduction of all analytes on an Hg electrode to ca. −1.50 V vs. Saturated Calomel Electrode (SCE). The proposed method, validated, and tested on 10 samples of honeys of different botanical origin and age, is fast and accurate, and, in the case of strawberry tree honey (Arbutus unedo), it highlighted the contribution to the FI of the homogentisic acid (HA), i.e., the chemical marker of the floral origin of this honey, which was quantitatively reduced in the working conditions. Excellent agreement between the SWV and Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC) data was observed in all samples considered

    CHAPTER 13. Assay of B Vitamins and other Water-soluble Vitamins in Honey

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    B Vitamins and Folate covers thiamine, riboflavin, pantothenic acid, pyridoxine, biotin, cobalamin and folate. The book begins with an overview covering the historical context of B vitamins, disease and fortification effects. Coverage then includes chemistry, biochemistry and metabolism across the vitamins and related compounds; analysis including spectrofluorimetry, isotope dilution mass spectrometry, chromatography; and finishes with the functional effects in humans including in strokes, epilepsy, dementia and kidney disease. Written by an expert team, this book provides a fascinating insight for those with an interest in the health and nutritional science

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Conducting Polymers in Amperometric Sensors: A State of the Art over the Last 15 Years with a Focus on Polypyrrole-, Polythiophene-, and Poly(3,4-ethylenedioxythiophene)-Based Materials

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    Conducting polymers are used in a wide range of applications, especially in the design and development of electrochemical sensors. Their main advantage, in this context, is their ability to efficiently modify an electrode surface using the direct polymerization of a suitable monomer in an electrochemical cell, or by physical coating. Additionally, the conducting polymers can be mixed with further materials (metal nanoparticles, carbonaceous materials) to enhance conductivity and analytical features (linear range, limit of detection, sensitivity, and selectivity). Due to their characteristics, conducting polymer-based amperometric sensors are applied to the determination of different organic and inorganic analytes. A view of recent advances in this field focusing on pyrrole, thiophene, and 3,4-ethylenedioxythiophene as starting materials is reported
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