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.     

A Novel Approach for Bisphosphonates: Ionic Liquids and Organic Salts from Zoledronic Acid

Novel ionic liquids and organic salts based on mono- or dianionic zoledronate and protonated superbases, choline and n-alkylmethylimidazolium cations, were prepared and characterized by spectroscopic and thermal analyses. Most of the prepared salts display amorphous structures and very high solubility in water and saline solutions, especially the dianionic salts. Among the zoledronate-based ionic compounds, those containing choline [Ch] and methoxyethylmethylimidazolium [C₃OMIM] cations appear to have significant cytotoxicity against human osteosarcoma cells (MG63) and low toxicity toward healthy skin fibroblast cells. Because osteosarcoma is a bone pathology characterized by an increase in bone turnover rate, the results presented herein may be a promising starting point for the development of new ionic pharmaceutical drugs against osteosarcoma.     

Pharmacokinetic Parameters of HIV-1 Protease Inhibitors

Since the beginning of the HIV epidemic, research has been carried out to control the virus. Understanding the mechanisms of replication has given access to the various classes of drugs that over time have transformed AIDS into a manageable chronic disease. The class of protease inhibitors (PIs) gained notice in anti-retroviral therapy, once it was found that peptidomimetic molecules act by blocking the active catalytic center of the aspartic protease, which is directly related to HIV maturation. However, mutations in enzymatic internal residues are the biggest issue for these drugs, because a small change in biochemical interaction can generate resistance. Low plasma concentrations of PIs favor viral natural selection; high concentrations can inhibit even partially resistant enzymes. Food-drug/drug-drug interactions can decrease the bioavailability of PIs and are related to many side effects. Therefore, this review summarizes the pharmacokinetic properties of current PIs, the changes when pharmacological boosters are used and also lists the major mutations to help understanding of how long the continuous treatment can ensure a low viral load in patients.     

Theoretical and experimental studies of a new aniline derivative corrosion inhibitor for mild steel in acid medium

4-Chloro-N-(pyridin-2-ylmethyl)aniline (CPYA) was synthesized by a simple and inexpensive method and tested as a corrosion inhibitor in acid medium for mild steel by using gravimetric studies and electrochemical measurements. An average maximum efficiency of 96.0% was achieved at 4.59 mmol/L. Corrosion kinetic and thermodynamic parameters were also analyzed. Surface analyses (atomic force microscopy and scanning electron microscopy) show that protection is enabled by adsorption on the metal, forming a film. Quantum chemical calculations were performed to access information regarding the molecular structure in the corrosive medium and to support interpretation of the results obtained by experimental methods.     

Extracellular Vesicles in CNS Developmental Disorders

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.     

New Eugenol Derivatives with Enhanced Insecticidal Activity

Eugenol, the generic name of 4-allyl-2-methoxyphenol, is the major component of clove essential oil, and has demonstrated relevant biological potential with well-known antimicrobial and antioxidant actions. New O-alkylated eugenol derivatives, bearing a propyl chain with terminals like hydrogen, hydroxyl, ester, chlorine, and carboxylic acid, were synthesized in the present work. These compounds were later subjected to epoxidation conditions to give the corresponding oxiranes. All derivatives were evaluated against their effect upon the viability of insect cell line Sf9 (Spodoptera frugiperda), demonstrating that structural changes elicit marked effects in terms of potency. In addition, the most promising molecules were evaluated for their impact in cell morphology, caspase-like activity, and potential toxicity towards human cells. Some molecules stood out in terms of toxicity towards insect cells, with morphological assessment of treated cells showing chromatin condensation and fragmentation, which are compatible with the occurrence of programmed cell death, later confirmed by evaluation of caspase-like activity. These findings point out the potential use of eugenol derivatives as semisynthetic insecticides from plant natural products.     

Functionalized-radiolabeled hydroxyapatite/tenorite nanoparticles as theranostic agents for osteosarcoma

Hydroxyapatite (HA) nanoparticles (NPs) doped with different radioisotopes for use as theranostic systems play an important role in scientific research nowadays due to their ability to simultaneously act in the treatment and diagnosis of various types of cancers. In this work, we describe the synthesis and characterization of a hydroxyapatite/tenorite nanocomposite functionalized with folic acid, representing a nanotheranostic material with potential for application as an agent in positron emission tomography imaging systems and to act specifically in the treatment and diagnosis of osteosarcoma. ⁶⁴Cu and ³²P were produced by nuclear activation in the TRIGA reactor at CDTN. The obtained samples were characterized by XRD with Rietveld refinement, XAFS, SEM, BET, TGA, FTIR, CHN, ICP-AES, XPS and gamma spectroscopy. We investigated how CuO grows in HA NPs, the stability of the interactions between CuO and HA constituents and the interactions between folic acid and the surface of the HA NPs. The results indicate the formation of a second phase (tenorite) besides hydroxyapatite, and that the interactions between the two phases are stable, resulting in a nanocomposite. Furthermore, the activation of ⁶⁴Cu and ³²P inside the HA matrix, through the exposition to a neutron flux, produces a theranostic material of interest for biological tests.     

Design and synthesis of foam glasses from recycled materials

Recycling has emerged as an environmental key point due to the diminishing of natural resources and the generation of ever-increasing amounts of industrial solid wastes. Glass wastes are among the materials that attract great interest in the recycling concept. This work presents the results of foams production from four series of compositions. The first series comprises powders of a sodium-calcium-silicate sheet glass cullet as the main component, an alkali-earth aluminosilicate glass as an additive, and a reagent grade silicon carbide (SiC) powder as gassing agent. In the second series, the glass cullet was used in combination with fly ashes (FLA) as main components, while SiC waste from abrasive paper served as foaming agent. In the third and fourth series, carbonates (calcite and dolomite) were used for foaming powder mixtures composed of sheet glass cullet and FLA, and powdered cathode ray tube panel glasses, respectively. All the processing parameters, including the main components, the nature and content of foaming agents are shown to play a crucial role on the foaming ability and final properties of the glass foams.     

Composites based on high-density polyethylene,polylactide and calcium carbonate: effect of calcium carbonate nanoparticles as co-compatibilizers

Polymer Bulletin - Investigating the compatibility mechanism of hybrid composites based on two polymers and one mineral nanofiller is a challenge that needs to be better understood. This study...