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.     

Impact of high-intensity ultrasound on physical properties and degree of oxidation of lipase modified menhaden oil with caprylic acid and/or stearic acid

The purpose of this research was to determine the effect of high-intensity ultrasound (HIU) on physical properties, degree of oxidation, and oxidative stability of structured lipids (SLs). Caprylic acid (C) and stearic acid (S) were incorporated into menhaden oil using Lipozyme® 435 lipase to obtain five samples: (1) LC 20 (menhaden oil with 20% of C), (2) LC 30 (menhaden oil with 30% C), (3) LS 20 (menhaden oil with 20% S), (4) LS 30 (menhaden oil with 30% S), and (5) Blend C (menhaden oil with 16.24% C and 13.04% S). Samples were crystallized for 90 min at the following temperatures: (1) LC 20 at 15.5°C, (2) LC 30 at 17.5°C, (3) LS 20 at 24°C, (4) LS 30 at 30°C, and (5) Blend C at 18.0°C, and HIU was applied at the onset of crystallization. Physical properties, degree of oxidation, and oxidative stability were evaluated in sonicated and nonsonicated samples. All SLs had statistically higher G′ after sonication. Sonicated LS 30, LC 30, and Blend C had a higher melting enthalpy than the nonsonicated ones, while enthalpy values in sonicated LS 20 and LC 20 samples were not statistically different than the nonsonicated ones. No significant difference between sonicated and nonsonicated samples was observed in peroxide values (1.2 ± 0.1 meq/kg, p > 0.05) and in the oxidative stability index (6.3 ± 0.2 h, p > 0.05). These results showed that HIU was effective at changing physical properties without affecting the oxidation of the samples.     

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.     

Mechanism of thermochemical growth of iron borides on iron

The mechanism of thermochemical growth of iron borides on iron was studied by analysing the products which form on samples placed in contact with B₄C-base powder mixtures with different boronising potential. The analyses were carried out by means of metallographic and X-ray diffraction techniques. Three subsequent stages of growth were observed which explain the occurrence of typical properties of the thermochemically grown boride coatings, such as preferred crystallographic orientations and textures, as well as mechanical compactness and hardness, which play a determining role in the tribological behaviour of borided components.     

Ganglioside content of human platelets--differences in resting and activated platelets

Gangliosides may play functional roles in platelet physiology, therefore this study has been designed to evaluate whether changes in ganglioside composition may occur as a consequence of platelet activation. The results obtained indicate that lactosylceramide and GM3 are the major glycosphingolipids of human platelets. The lipid-bound sialic acid (LBSA) content was 1.27 +/- 0.04 micrograms/mg of protein. Resting platelets did not express GD3; GD3 was synthesized upon platelet activation (24 +/- 8 ng/mg of protein). The stimulation of platelets with adenosine diphosphate showed the appearance of GD3 even in the absence of degranulation. Finally, incorporation of pyrene-labeled GM3 into platelet membranes, followed by stimulation with adenosine diphosphate, resulted in the appearance of a fluorescent band comigrating with GD3. The present studies indicate that sialytransferase activation may occur as an early event following platelet stimulation, leading to GD3 synthesis mainly from the GM3 pool.     

The combined use of ultrasound and densitometry in the prediction of vertebral fracture

Measurement of ultrasonographic parameters provides information concerning not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density for evaluating the probability of vertebral fracture. 397 postmenopausal women (59.1 +/- 6.0 years) with (n = 178) or without (n = 219) atraumatic vertebral fractures were studied. In all women, bone mineral density (BMD) of the lumbar spine was evaluated by dual X-ray absorptiometry (DXA) and speed of sound (SOS); broadband ultrasound attenuation (BUA) and Stiffness in the calcaneus were evaluated by an Achilles unit (Lunar Corporation). Ultrasonographic parameters and BMD were compared by examining the magnitude of the odds ratios, to determine which produces the highest estimate of the probability of odds of fracture, and by examining widths of the respective confidence intervals (CI) to show which estimate of odd ratio is the most precise. The relative risk of vertebral fracture, after adjusting for potential confounders, was 3.5 (CI 2.6-4.8) for BUA; 4.5 (CI 3.2-6.2) for SOS; 5.8 (CI 4.0-8.4) for Stiffness and 7.5 (CI 4.8-11.5) for BMD. Ultrasound (US) parameters were still significant independent predictors of vertebral fracture, even after adjusting for BMD. The relative risk of fracture for a simultaneous decrease by 1 SD of BMD and by 1 SD of each ultrasound parameter was 17.3 (CI 9.4-39.6) for BMD and SOS; 18.3 (CI 8.4-30.6) for BMD and BUA and 22.1 (CI 8.9-52.7) for BMD and Stiffness. Our data suggest that US and BMD provide complementary information which can be combined to improve estimates of vertebral fracture risk.     

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.     

Genotoxic effect of Physalis angulata L. (Solanaceae) extract on human lymphocytes treated in vitro

Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose different extracts and infusions are commonly used in the popular medicine for the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However, the genotoxic effects of P. angulata on human cells is not well known. The main purpose of the present study was to evaluate the in vitro genotoxic effects of aqueous extract of P. angulata using the comet assay and the micronucleus assay in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata extracts were performed in vitro in order to access the extent of DNA damage. The comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and 6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P. angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed a statistically significant increase in the frequency of micronucleus (p<0.05), however, the cytokinesis blocked proliferation index (CBPI) was not decreased after P. angulata treatment. In conclusion, the present work demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro.