Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.     

Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.     

Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.     

Inferring kinetic dissolution of NaCl in aqueous glycol solution using a low-cost apparatus and population balance model

An experimental methodology for inferring brine dissolution rate in monoethylene glycol (MEG) solutions at different temperatures using a webcam combined with a mathematical model is presented. The measurement system is designed to track the RGB (red, green, and blue) colour variations during the dissolution process. A dynamic model augmented with the population balance equation is applied to describe the dissolution process. Moreover, the dissolution rate is consistently related to the temperature and MEG concentration through the driving force based on the Gibbs energy and chemical affinity. The applied low-cost measurement apparatus proved to be a useful resource for tracking the dissolution dynamics in a wide range of undersaturation.     

Reasons for personnel turnover in a private health facility

In this article 1 describe efforts to build a genetically informative, population-based sample of black twins to study physical frailty and aging in the United States. This project involves the use of governmental registries combined with sampling techniques developed to overcome limitations in the registry data. Two analytical approaches to measures of disability are included to illustrate the types of questions that can be addressed with this sample. These results suggest that physical disability in late life has both genetic and environmental determinants. Only with a genetically informative sample can evidence be collected indicating that frailty may be driven by fixed processes (i.e., disability resulting from activation of senescence genes), fluid processes (i.e., disability resulting from changes in the features of the environment), or a combination of both.     

Carbon fibre cloth as an electrode material: electrical conductivity and mass transfer

The paper deals with carbon fibre cloth electrodes, employed in the fabrication of composite materials. The electrical conductivity of single bundles, groups of bundles and cloth is studied. Ohm's law applies to the electrical conduction in the direction of the fibre length, but bundle conductivity decreases with the number of fibres in the bundle. Electrochemical mass transfer between a flowing electrolyte and a cloth arranged as a flow-through or a flow-by porous electrode indicates the existence of double porosity in the material. Due to double porosity, only the external surface of the cloth works as an electrode. This finding shows that the material is not suitable for such an application.     

Polymerization strategies to overcome limiting monomer conversion in silicone-acrylic miniemulsion polymerization

The limiting conversion phenomenon observed in high solid content silicone-modified acrylic miniemulsion polymerizations was investigated. It was found that the limiting conversion was mainly due to the formation of inactive radicals upon propagation of butyl acrylate radicals with the vinyl end groups of the polydimethylsiloxane. Polymerization strategies that allowed overcoming this problem and achieving high monomer conversion were implemented.