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.     

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.     

Early and intensive physiotherapy accelerates recovery postarthroscopic meniscectomy: results of a randomized controlled study

The efficacy of an early, intensive, supervised rehabilitation program to accelerate knee strength recovery in the first 3 weeks postmeniscectomy by arthroscopy was evaluated using a randomized controlled trial design. The maximal voluntary isokinetic strength of 31 men, randomly allocated to either a treatment (EXP) or a control (CTL) group, was measured twice by a blind rater: preoperatively (pretest) and 3 weeks postsurgery (posttest), using a computer-controlled Kin-Com dynamometer (Chattecx Corporation, Chattanooga, TN). Strength deficits of the operated leg at the pretest and posttest were established in percent of the values obtained for the sound leg at the pretest. In the interval between the surgery and the posttest, the patients of the EXP group (n = 15) received nine supervised treatments combined to home exercises whereas patients of the control group (n = 16) had no specific physiotherapy treatment but were given instructions in postsurgical management and prescribed exercises by the orthopedic surgeons. Patients of the EXP group had better knee extensor strength recovery than patients of the CTL group (ANCOVA, p < 0.001). The size of the strength difference (3 weeks postsurgery) between EXP and CTL subgroups (n = 8) matched according to preoperative deficits was as large as 26% and the residual deficits of the untreated patients were two to three times larger than those of the treated patients. The results of this study highlight the importance of instituting an early intensive and supervised rehabilitation program, especially for workers returning to a strenuous job requiring good knee extensor muscle function.     

New species of Aeromonas isolated in Cuba

One hundred and fifty-five strains of Aeromonas isolated in the stools of children under 5 years presenting with acute diarrheal disease were studied. Using the Aerokey II system for the identification of species, 47 strains were identified as Aeromonas caviae, 58 as Aeromonas hydrophila, 23 as Aeromonas veronii biovar sobria, 14 as Aeromonas trota, 9 as Aeromonas veronii biovar veronii, 2 as Aeromonas jandaei and 2 as Aeromonas shubertii, Emphasis is placed on the advantages of this method which allowed for the classification of new species not identified previously in our country.