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Clinic fees of immunopreventable ailments in the economically energetic human population throughout Brazil.
Finally, our data indicated that the pro-apoptotic effect of Pum2 was dependent on Sirt1 and AMPK. Collectively, our results provide the evidence that Pum2-mediated Sirt1 mRNA decay plays a detrimental role in H/R-induced cardiomyocytes injury.Objectives Cisplatin is commonly applied as anticancer agent for various cancers, including ovarian cancer. Unfortunately, the drug resistance frequently occurred which obstructing the effect of cisplatin on tumors. The goal of our research was to investigate the reversal actions and the potential mechanisms of sulforaphane (SFN) on cisplatin resistance in ovarian carcinoma. Methods The A2780 and IGROV1 cells and their cisplatin resistance cells A2780/CP70 and IGROV1-R10 were used in this study. Cell viability was detected by CCK-8. The DNA repair was measured by comet assay. The cisplatin transporter proteins were measured with western blotting. The concentration of intracellular cisplatin was detected by HPLC. The luciferase activity assay was applied to determine the target site of miR-30a-3p on the 3'UTR of ERCC1 and ATP7A. A2780/CP70 and IGROV1-R10 xenograft mouse model were established to confirm the antineoplastic action of SFN combined with cisplatin. Results SFN reversed the resistance of A2780/CP70 and IGROV1-R10 ovarian carcinoma cells to cisplatin through inducing DNA damage and accumulation of intracellular cisplatin. SFN treatment notably increased miR-30a-3p expression, which was decreased in cisplatin-resistant cells. Moreover, overexpressed miR-30a-3p enhanced the sensitivity of A2780/CP70 and IGROV1-R10 cells to cisplatin treatment, and inhibiting miR-30a-3p activity abated the reversal actions of SFN on cisplatin resistance. The luciferase assay findings showed that miR-30a-3p binds to ERCC1 and ATP7A which are the key regulators for DNA repair and cisplatin transportation. Conclusions Our findings indicated that SFN could enhance cisplatin sensitivity of ovarian carcinoma cells through up-regulating miR-30a-3p to induce DNA damage and accumulation of intracellular cisplatin.Background and aims Endoscopic radiofrequency ablation (RFA) is a new ablative treatment for unresectable extrahepatic cholangiocarcinoma (EHCC). A novel 5-fluorouracil compound (S-1TM) has been widely used as one of the key drugs with first-line or second-line chemotherapy for the treatment of advanced cholangiocarcinoma. The aim of this study is to evaluate the clinical efficacy and safety of endoscopic RFA combined with S-1 for the treatment of unresectable locally advanced EHCC. Methods Patients with unresectable EHCC were prospectively randomized to 1 of 2 groups the RFA + S-1 group and the RFA group. SB431542 in vivo Median overall survival (OS), stent patency time, karnofsky performance status (KPS) score, and adverse events rate were analyzed. Results (1) The median OS was longer in the RFA + S-1 group (n=37) than that in the RFA group (n=38) (16.0; 95% CI, 13.1-19.0 vs 11.0; 95% CI, 9.7-12.3 months; P0.05). Conclusion For the treatment of locally advanced EHCC, endoscopic RFA combined with S-1 is associated with longer survival and stent patency, and improved functional status than RFA alone.Homo-oligomerisation of proteins is a ubiquitous phenomenon whose exact role remains unclear in many cases. To identify novel functions, this paper provides an exploration of general dynamical mathematical models of homo-oligomerisation. Simulation and analysis of these models show that homo-oligomerisation on its own allows for a remarkable variety of complex dynamic and steady state regulatory behaviour such as transient overshoots or homeostatic control of monomer concentration. If post-translational modifications are considered, however, conventional mass action kinetics lead to thermodynamic inconsistencies due to asymmetric combinatorial expansion of reaction routes. Introducing a conservation principle to balance rate equations re-establishes thermodynamic consistency. Using such balanced models it is shown that oligomerisation can lead to bistability by enabling pseudo-multisite modification and kinetic pseudo-cooperativity via multi-enzyme regulation, thereby constituting a novel motif for bistable modification reactions. Due to these potential signal processing capabilities, homo-oligomerisation could play far more versatile roles in signal transduction than previously appreciated.Understanding the impact of eutrophication on the dynamics of aquatic food webs, remains a long-term challenge in ecology. Mathematical models generally predict the destabilisation of such webs, under increasing eutrophication levels, with large oscillations of species densities that can result in their extinction. This is at odds with a number of ecological observations that show stable dynamics even for high nutrient loads. The apparent discrepancy between theory and observations is known as the Rosenzweig's 'paradox of enrichment' and various solutions to the problem have been proposed over the years. In this study, we explore the stabilisation of dynamics of a tri-trophic plankton model in a eutrophic environment which occurs as a result of interplay of space heterogeneity, ecological stoichiometry, and food taxis of predators. We build a variety of models of increasing complexity, to explore various scenarios of phytoplankton growth, zooplankton food-dependent vertical movement, and different stoichiometric limitations of zooplankton. We show that the synergy among the vertical gradient in phytoplankton growth, phytoplankton structuring in terms of their stoichiometric ratio, and food-dependent vertical movement of zooplankton, would result in a postponing of destabilisation of eutrophic systems as compared to a well-mixed system. Our approach reveals a high complexity of the bifurcation structure of the system when key model parameters, such as the degree of eutrophication and light shading, are varied. We find coexistence of limit cycles and stable equilibria and that the possibility of multiple attractors in the system can result in hysteresis phenomena when the nutrient load is manipulated. These results are relevant and should be taken into account in lake restoration programs.
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