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.     

Mechanical spectroscopy in commercial Fe–6 wt.% Si alloys between 400 and 1000 K

Mechanical spectroscopy, neutron diffraction and differential scanning calorimetry (DSC) were performed on commercial Fe–6 wt.% Si alloy after quenching from high temperature. The damping spectrum shows a peak at around 800 K and an associated modulus defect. The modulus shows an increase during the second and subsequent heating runs. In addition, an anomaly in the modulus behavior has been found at around 400 K. Different thermal treatments allows to obtain two different recovery degrees of the quenched-in defects. The influence of the recovery degree on the 800 K internal friction peak and on the anelastic modulus has been evaluated and confirm the validity of the grain boundary mechanism associated to this peak. Experimental results are discussed on the basis of recovery and ordering processes.     

Frequency of molecular alterations in heterozygous beta-thalassemia in southern Spain and their relation to the hematologic phenotype

INTRODUCTION: Heterozygous beta-thalassemia manifests hematologically with microcytosis, reduced red blood cell hemoglobin concentration and high hemoglobin A2 levels. Almost all molecular alterations are due to point mutations. We attempt to determinate the frequency of that mutations in the Oriental Andalusia Area, and its relationship with the hematological phenotype. PATIENTS AND METHODS: We have studied 45 heterozygous patients. DNA samples were amplified by PCR, using the printers CD7 and HI1. A 16 Kb fragment corresponding to beta globin gene was obtained and analyzed by Dot Blot assay and hybridized with allelic specific oligonucleotide (ASO) probes to detect the 6 more frequent mutations found in the South of Spain. RESULTS: Codon 39 nonsense mutation (31.1%) was the most frequent finding followed by IVS-1 NT 110 (26.7%). The relationship between hematological parameters and molecular mutations concluded that IVS-I NT 6 mutation developed a minimal anemia. DISCUSSION: From the practical point of view, this study indicates that we were able to detect more than 90% of heterozygous beta-tal. with 5 out of 6 ASO probes used in this work. Thus, our data also provides a further implication in prenatal diagnosis.     

Polyimide foams from powder: Experimental analysis of competitive diffusion phenomena

In the present study, various diffusive processes have been investigated during foaming of powdered precursors of polyimide. A detailed analysis of the powdered precursor's characteristics allows for an enhanced morphological understanding of the resulting microstructures and foam unit cell. Parameters that are central to the foaming process such as particle morphology, volatile concentration and sorption-desorption processes are evaluated. Isothermal and non-isothermal desorption experiments have been carried out by thermogravimetric analysis (TGA), and specific diffusive processes have been correlated to thermodynamic and kinetic transitions by means of modulated differential scanning calorimetry (MDSC) of the corresponding materials. It was found that two primary fluxes of volatiles, one out of the external surface of the particles (responsible for volatile desorption) and the other into the growing bubble (responsible for vapor supersaturation inside the bubble) compete against each other creating a competitive scenario that becomes the controlling factor for potential inflation within the precursor particles.     

Magnetic resonance imaging of H, Na, and Cl penetration in Portland cement mortar

The first magnetic resonance imaging profiles of chloride content in low- and high-permeability Portland cement mortar have been obtained using a novel material science imaging technique. The penetration of water as well as chloride and sodium ions, into mortar specimens was monitored for a period of 72 h. Marked differences in penetration depth were observed in low- and high-permeability mortar. These preliminary experiments show significant differences between the extent and nature in the penetration of chlorides compared to water and sodium.     

Variation in Malting Quality and Heat Resistance in the Malting Barley Variety “Alexis”

In earlier studies concerning vigour, where subsamples are heat‐treated before germination there was found heat‐sensitive as well as heat‐resistant barley samples. The vigour model developed by Ellis and Roberts and further developed at Carlsberg, could only describe the heat‐sensitive barleys. Seventeen samples of the “Alexis” variety grown widely in Europe were collected from the EBC trials in 1994 in order to see if heat resistance in barley was influenced by different growing conditions. We found both heat‐sensitive samples following the vigour model as well as pronounced heat‐resistant samples, but these were not divided according to growing conditions. The germination curves dependent on heat treatment and germination time were evaluated by Principal Component Analysis (PCA). Heat‐resistant barley samples could be differentiated from heat‐sensitive samples already after ½ h of heat treatment at 68°C (12% moisture) and after 3 days of germination. The barley samples were analysed with regard to malting quality. The PCA evaluation of the data divided the samples according to growing location, mainly due to differences in protein and β‐glucan. However, the malting analyses could not describe the differences in heat resistance and sensitivity of the barleys. The biochemical background of the heat resistance found is discussed on the basis of literature. Our findings should give an experimental basis for exploiting a biochemical principle for heat resistance, which is formed during grain filling and consumed during storage and germination.     

Effect of Dilution and Porosity on Self-Propagating High-Temperature Synthesis of Silicon Nitride

Self-propagating high-temperature synthesis is a very easy and low-cost method to synthesize Si₃N₄. The nitriding of silicon powder takes place in a self-sustained regime under high pressures of nitrogen with dilution of silicon by Si₃N₄. In this work effects of dilution and green-mixture porosity on combustion velocity and phase content of reaction products are studied. Results are compared with previous work of other authors and different behaviors are found. An explanation of these behaviors is given.