Hyperglycaemia-induced resistance to Docetaxel is negated by metformin:a role for IGFBP-2

The incidence of many common cancers varies between different populations and appears to be affected by a Western lifestyle. Highly proliferative malignant cells require sufficient levels of nutrients for their anabolic activity. Therefore, targeting genes and pathways involved in metabolic pathways could yield future therapeutics. A common pathway implicated in energetic and nutritional requirements of a cell is the LKB1/AMPK pathway. Metformin is a widely studied anti-diabetic drug, which improves glycaemia in patients with type 2 diabetes by targeting this pathway. We investigated the effect of metformin on prostate cancer cell lines and evaluated its mechanism of action using DU145, LNCaP, PC3 and VCaP prostate cancer cell lines. Trypan blue dye-exclusion assay was used to assess levels of cell death. Western immunoblotting was used to determine the abundance of proteins. Insulin-like growth factor-binding protein-2 (IGFBP-2) andAMPKgenes were silenced using siRNA. Effects on cell morphology were visualised using microscopy.IGFBP-2gene expression was assessed using real-time RT-PCR. With DU145 and LNCaP cells metformin alone induced cell death, but this was reduced in hyperglycaemic conditions. Hyperglycaemia also reduced the sensitivity to Docetaxel, but this was countered by co-treatment with metformin. LKB1 was required for the activation of AMPK but was not essential to mediate the induction of cell death. An alternative pathway by which metformin exerted its action was through downregulation of IGFBP-2 in DU145 and LNCaP cells, independently of AMPK. This finding could have important implications in relation to therapeutic strategies in prostate cancer patients presenting with diabetes.</jats:p

Oxidation of cyclohexanol and cyclohexene with triazenido complexes of chromium immobilized in biosorption FAU supports

This work presents the recovery of biosorption supports as an alternative source of benign production of heterogeneous catalysts for oxidation reactions in mild conditions. Cr-containing FAU zeolite, in sodium form (NaY) and in proton form (HY), was recovered from biosorption studies and reused as support for the preparation of heterogeneous catalysts by the flexible ligand method, using 1,3-diphenyltriazene derivatives. Results showed that the ligand play an important role in the coordination of Cr inside the zeolite. The catalysts showed good activity for the oxidation of cyclohexanol, reaching a maximum of 63.5% conversion. Cr leaching was evaluated and it was found that the Cr-FAU supports lost some of the Cr into the reaction medium, whereas immobilization of Cr-complexes reduced the referred leaching. For the cyclohexene oxidation, a maximum 72.9% conversion was achieved with a HY zeolite-based catalyst.H. Figueiredo and B. Silva are thankful to the "FCT - Fundacao para a Ciencia e Tecnologia" for their respective research grants. IKB thanks FO' for the contract under the program Ciencia 2007. This work was partially funded by the Centre of Biological Engineering and the Centre of Chemistry (University of Minho, Portugal) through FCT strategic projects PEst-OE/EQB/LA0023/ 2013 and PEst-C/QUI/UI0686/2011 (nF-COMP-01-0124-FEDER022716), the Project "BioEnv - Biotechnology and Bioengineering for a sustainable world", REF. NORTE-07-0124-FEDER-000048, co-funded by the Programa Operacional Regional do Norte (ON.2 - 0 Novo Norte), QREN and FEDER, and by the Spanish Ministry of Science and Innovation (CTQ2008-04261/PPQ)

From waste to value: electrocatalytic reduction of nitrate into ammonia at mono and bimetallic-CNT modified electrodes

The electrochemical transformation of nitrate ions into ammonia (NH3), which ranks among the most widely employed chemicals globally, using mono (Pd, Pt) and bimetallic catalysts (Pd-Cu, Pt-Cu, Ru-Cu) supported on carbon nanotubes (CNT) was studied in acidic medium. The higher conversion and best selectivity towards NH3 corresponding, respectively, to 88 and 80% were found for Pt_CNT modified electrode, with an initial nitrate concentration of 12.9mM. The addition of copper as a second metal provides lower percentage of ammonia in comparison with the monometallic Pt_CNT and Pd_CNT electrocatalysts. The prepared electrocatalysts show good mechanical and chemical stability, under the experimental conditions. Principal Component Analysis (PCA) was carried out in order to highlight the effect of experimental parameters on selectivity.info:eu-repo/semantics/publishedVersio

A genome-wide association study of antidepressant-induced mania

Antidepressant-induced mania (AIM) is a side effect of antidepressant treatment that is characterized by mania or hypomania after the start of medication. It is likely polygenic, but its genetic component remains largely unexplored. We aim to conduct the first genome-wide association study of AIM in 814 bipolar disorder patients of European ancestry. We report no significant findings from our single-marker or gene-based analyses. Our polygenic risk score analyses also did not yield significant results with bipolar disorder, antidepressant response, or lithium response. Our suggestive findings on the hypothalamic-pituitary-adrenal axis and the opioid system in AIM require independent replications

Bisphenol A exposure and cardiac electrical conduction in excised rat hearts

BACKGROUND: Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased BPA urinary concentrations and cardiovascular disease; yet the direct effects of BPA on the heart are unknown. OBJECTIVES: The goal of our studies was to measure BPA\u27s effect (0.1-100 μM) on cardiac impulse propagation ex vivo, using excised whole hearts from adult rats. METHODS: We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. RESULTS: Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1 - 100 μM), prolonged action potential duration (1 - 100 μM) and delayed atrioventricular conduction (10 - 100 μM). Importantly, these effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals, dropped ventricular beats and eventually resulted in complete heart block. CONCLUSIONS: Our results show that acute BPA exposure slows electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA\u27s effect on heart electrophysiology and determining whether chronic in vivo exposure can cause/exacerbate conduction abnormalities in patients with pre-existing heart conditions and other high-risk populations