α-Glucosidase, α-amylase inhibition kinetics,in vitro gastro-intestinal digestion,and apoptosis inducing abilities of Ficus microcarpa L. f. and Ficus racemosa L. fruit polysaccharides

Food Science and Biotechnology - A rich source of nutrients, figs have a number of clinically validated benefits. This study aimed to evaluate the in vitro simulated gastrointestinal digestion, and...     

Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche

Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences.     

Description of the thermodynamic properties and fluid-phase behavior of aqueous solutions of linear,branched, and cyclic amines

The SAFT-γ Mie group-contribution equation of state is used to represent the fluid-phase behavior of aqueous solutions of a variety of linear, branched, and cyclic amines. New group interactions are developed in order to model the mixtures of interest, including the like and unlike interactions between alkyl primary, secondary, and tertiary amine groups (NH₂, NH, N), cyclic secondary and tertiary amine groups (cNH, cN), and cyclic methine-amine groups (cCHNH, cCHN) with water (H₂O). The group-interaction parameters are estimated from appropriate experimental thermodynamic data for pure amines and selected mixtures. By taking advantage of the group-contribution nature of the method, one can describe the fluid-phase behavior of mixtures of molecules comprising those groups over broad ranges of temperature, pressure, and composition. A number of aqueous solutions of amines are studied including linear, branched aliphatic, and cyclic amines. Liquid–liquid equilibria (LLE) bounded by lower critical solution temperatures (LCSTs) have been reported experimentally and are reproduced here with the SAFT-γ Mie approach. The main feature of the approach is the ability not only to represent accurately the experimental data employed in the parameter estimation, but also to predict the vapor–liquid, liquid–liquid, and vapor–liquid–liquid equilibria, and LCSTs with the same set of parameters. Pure compound and binary phase diagrams of diverse types of amines and their aqueous solutions are assessed in order to demonstrate the main features of the thermodynamic and fluid-phase behavior.     

Chromium evaporation and oxidation characteristics of alumina-forming austenitic stainless steels for balance of plant applications in solid oxide fuel cells

The chromium (Cr) evaporation behavior of several different types of iron (Fe)-based AFA alloys and benchmark Cr₂O₃-forming Fe-based 310 and Ni-based 625 alloys was investigated for 500 h exposures at 800 °C to 900 °C in air with 10% H₂O. The Cr evaporation rates from alumina-forming austenitic (AFA) alloys were ~5 to 35 times lower than that of the Cr₂O₃-forming alloys depending on alloy and temperature. The Cr evaporation behavior was correlated with extensive characterization of the chemistry and microstructure of the oxide scales, which also revealed a degree of quartz tube Si contamination during the test. Long-term oxidation kinetics were also assessed at 800 to 1000 °C for up to 10,000 h in air with 10% H₂O to provide further guidance for SOFC BOP component alloy selection.     

Activity-Directed Synthesis: A Flexible Approach for Lead Generation

Activity-directed synthesis (ADS) is a structure-blind, functional-driven molecular discovery approach. In this Concept, four case studies highlight the general applicability of ADS and showcase its flexibility to support different medicinal chemistry strategies. ADS deliberately harnesses reactions with multiple possible outcomes, and allows many chemotypes to be evaluated in parallel. Resources are focused on bioactive molecules, which emerge in tandem with associated synthetic routes. Some of the future challenges for ADS are highlighted, including the realisation of an autonomous molecular discovery platform. The prospects for ADS to become a mainstream lead generation approach are discussed.     

In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Indoor heterogeneous photochemistry of furfural drives emissions of nitrous acid

People spend approximately 80% of their time indoor, making the understanding of the indoor chemistry an important task for safety. The high surface-area-to-volume ratio characteristic of indoor environments leads the semi-volatile organic compounds (sVOCs) to deposit on the surfaces. Using a long path absorption photometer (LOPAP), this work investigates the formation of nitrous acid (HONO) through the photochemistry of adsorbed nitrate anions and its enhancement by the presence of furfural. Using a high-resolution proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS), this work also investigates the surface emissions of VOCs from irradiated films of furfural and a mix of furfural and nitrate anions. Among the emitted VOCs, 2(5H)-furanone/2-Butenedial was observed at high concentrations, leading to maleic anhydride formation after UV irradiation. Moreover, the addition of potassium nitrate to the film formed NO_x and HONO concentrations up to 10 ppb, which scales to ca. 4 ppb for realistic indoor conditions. This work helps to understand the high levels of HONO and NO_x measured indoors.     

A closed-form solution for the distribution of the sum of Nakagami-m random phase vectors

The distribution of the modulus of the sum of random phase vectors, is of great practical importance in several applications which deal with sums of sinusoidal signals (wireless multipath transmissions, radars, optical communications, etc). In this letter, simple closed-form expressions are presented for the probability density function (PDF), the cumulative distribution function (CDF), the moment generating function (MGF) and the moments of the envelope distribution of the sum of L non-identical random Nakagami-m phase vectors with integer fading parameters. Moreover, the average over this distribution of the Gaussian Q-function and of the squared Q-function, are also presented in closed-form