Destabilizing the interplay between miR-1275 and IGF2BPs by Tamarix articulata and quercetin in hepatocellular carcinoma

Insulin-like growth factor-2 binding proteins (IGF2BPs) are oncogenic RNA-binding proteins, highly up-regulated in HCC, and were recently validated as direct targets of the tumour suppressor miR-1275. It is worth noting that around 47% of FDA approved anticancer drugs are derived from plants. Modulation by miRNAs and their cellular signalling cascades could constitute new pathways by which these phytochemicals exert their effects. This study aimed to investigate the potential use of Tamarix articulata, quercetin and epigallocatechin gallate (EGCG) in HCC and how these phytochemicals could epigenetically modulate the IGF axis using their impact on miR-1275. T. articulata ethyl acetate fraction significantly reduced the viability of Huh-7 cells compared to control cells. Treatment with T. articulata ethyl acetate fraction, quercetin and EGCG significantly enhanced miR-1275, while suppressed IGF2BP1 and IGF2BP3 mRNA expression levels. In summary, T. articulata, quercetin and EGCG have important implications for HCC molecular-targeted therapy through destabilizing the interplay between miR-1275 and the IGF axis.     

A single microcystin in a toxic Microcystis bloom from the river Río de la Plata (Argentina)

Microcystis is one of the most common bloom-forming cyanobacteria genera in diverse ecosystems. More than 80% of its strains are toxic, mainly due to their ability to produce metabolites known as microcystins (MC). Here we report on a M. aeruginosa bloom that appeared in the summer of 2001 at a site of the Río de la Plata, within the city of Buenos Aires. The symptoms in mice indicated that the bloom was hepatotoxic. LC-PDA analysis revealed a similar high concentration (0.9–1?mg?g^–1?d w) of just one MC in the bloom biomass during the 3-month study period. During this period most of the MC (ca. 98 %) was found intracellularly, and the content remained almost the same. The molecular mass of the bloom MC was 1036?Da, as deduced from LC-ESI-MS data. Fragment ion analysis by LC-IT-MS-MS allowed identifying 6 out of the 7 amino acids, as well as their position in the molecule. The molecular mass of the unidentified amino acid residue was 155?Da. According to the data obtained, the MC under study was MC-XR, X representing the unidentified amino acid. This is the first report both on the characterisation of MCs in an urban site of the Río de la Plata waters, and on an Argentinean bloom exhibiting only one MC variant.     

Numerical Eulerian method for linearized gas dynamics in the high frequency regime

We study the propagation of an acoustic wave in a moving fluid in the high frequency regime. We calculate the asymptotic approximation of the solution, around a mean flow, of this problem using an Eulerian method. By introducing the stretching matrix (deformation tensor for the geometrical optics rays) of the linearized Euler system, we deduce the geometrical spreading. This quantity is the key tool for computing the leading order term of the asymptotic expansion thanks to a conservation equation along the group velocity. The main contribution is to construct and implement a numerical scheme in the Eulerian framework for the eikonal equation and for the transport equation on the stretching matrix. We present numerical results for several test cases to study the convergence and validate our approach.     

On the average of the number of imaginary quadratic fields with a given class number

Let \(\mathcal {F}(h)\) be the number of imaginary quadratic fields with class number h. In this note, we improve the error term in Soundararajan’s asymptotic formula for the average of \(\mathcal {F}(h)\). Our argument leads to a similar refinement of the asymptotic for the average of \(\mathcal {F}(h)\) over odd h, which was recently obtained by Holmin, Jones, Kurlberg, McLeman and Petersen.     

E-Convex Sets, E-Convex Functions, and E-Convex Programming

A class of sets and a class of functions called E-convex sets and E-convex functions are introduced by relaxing the definitions of convex sets and convex functions. This kind of generalized convexity is based on the effect of an operator E on the sets and domain of definition of the functions. The optimality results for E-convex programming problems are established.     

Comparing partitions of two sets of units based on the same variables

We propose a procedure based on a latent variable model for the comparison of two partitions of different units described by the same set of variables. The null hypothesis here is that the two partitions come from the same underlying mixture model. We define a method of “projecting” partitions using a supervised classification method: once one partition is taken as a reference; the individuals of the second data set are allocated to the clusters of the reference partition; it gives two partitions of the same units of the second data set: the original and the projected one and we evaluate their difference by usual measures of association. The empirical distributions of the association measures are derived by simulation.     

A methoxylated quercetin glycoside harnesses HCC tumor progression in a TP53/miR-15/miR-16 dependent manner

Abstract

This study focused on studying the impact of flavonoids isolated from Cleome droserifolia on HCC cell lines and to further unveil their possible impact on TP53 and its downstream tumor suppressor miRNAs. Three flavonol glycosides were isolated from C. droserifolia namely, Isorhamnetin-3-O-β-D-glucoside (1), Quercetin-3`-methoxy-3-O-(4``-acetylrhamnoside)-7-O-α-rhamnoside (2), and Kaempferol-4`-methoxy-3,7-O-dirhamnoside (3). They showed a concentration and time dependent reduction in cellular viability and anchorage-independent growth of HCC cells. Moreover, they exhibited a decrease in the migrating capacity of HepG2 cells in a pattern similar to positive control cells. (2) Showed the most potent effects in halting HCC tumorigenic activity (IC₅₀=36?±?1.70?µM) and a repression of the cellular proliferation rate of HepG2 cells. Restoration of TP53 and its downstream tumor suppressor miRNAs; miR-15a, miR-16, miR-34a by (2) was observed. Moreover, attenuation of (2) mediated actions was shown upon using anti-miR-15a and anti-miR-16. To conclude, this study crystallizes a novel role of C. droserifolia in harnessing HCC progression in-vitro with a possible contribution of TP53/miR-15a/miR-16.     

CHARACTERIZATION OF EFFICIENT SOLUTIONS FOR MULTI-OBJECTIVE OPTIMIZATION PROBLEMS INVOLVING SEMI-STRONG AND GENERALIZED SEMI-STRONG E-CONVEXITY

The authors of this article are interested in characterization of efficient solutions for special classes of problems. These classes consider semi-strong E-convexity of involved functions. Sufficient and necessary conditions for a feasible solution to be an efficient or properly efficient solution are obtained.