Evaluation of Epigenetic and Radiomodifying Effects during Radiotherapy Treatments in Zebrafish

Radiotherapy is still a long way from personalizing cancer treatment plans, and its effectiveness depends on the radiosensitivity of tumor cells. Indeed, therapies that are efficient and successful for some patients may be relatively ineffective for others. Based on this, radiobiological research is focusing on the ability of some reagents to make cancer cells more responsive to ionizing radiation, as well as to protect the surrounding healthy tissues from possible side effects. In this scenario, zebrafish emerged as an effective model system to test for radiation modifiers that can potentially be used for radiotherapeutic purposes in humans. The adoption of this experimental organism is fully justified and supported by the high similarity between fish and humans in both their genome sequences and the effects provoked in them by ionizing radiation. This review aims to provide the literature state of the art of zebrafish in vivo model for radiobiological studies, particularly focusing on the epigenetic and radiomodifying effects produced during fish embryos’ and larvae’s exposure to radiotherapy treatments.     

Do Scleractinian Corals Engage in Chemical Warfare Against Microbes?

Corals are constantly exposed to ubiquitous microbes. Detrimental effects of microbes on corals include surface fouling and disease. To prevent fouling and disease, corals need to resist microbial colonization and invasion. One way that this could be achieved is by chemical defense. Extracts from 100 scleractinian coral species (44 genera and 13 families) were screened for antimicrobial activity against seven microbe species (Alteromonas rubra, Photobacterium damsela, Vibrio harveyi, Vibrio alginolyticus, Vibrio parahaemolyticus, Synechococcus sp., and Staphylococcus aureus). Activity against Synechococcus sp. (a marine cyanobacterium) was recorded in 100 coral species, and eight of these coral species also inhibited the growth of marine bacteria. The extent of microbial colonization on coral surfaces was assessed in 20 scleractinian species to test the hypothesis that fewer microbes occur on corals that have antimicrobial compounds. Bacterial counts exceeded cyanobacterial counts on coral surfaces, and coral species with antibacterial activity had the fewest bacteria on their surfaces. Thus, corals with less heavily colonized surfaces chemically inhibit microbial colonization.     

Measuring gas hold-up in gas–liquid/gas–solid–liquid stirred tanks with an electrical resistance tomography linear probe

An electrical resistance tomography (ERT) linear probe was used to measure gas hold-up in a two-phase (gas–liquid) and three phase (gas–solid–liquid) stirred-tank system equipped with a Rushton turbine. The ERT linear probe was chosen rather than the more commonly used ring cage geometry to achieve higher resolution in the axial direction as well as its potential for use on manufacturing plant. Gas-phase distribution was measured as a function of flow regime by varying both impeller speed and gas flow rate. Global and local gas hold-up values were calculated using ERT data by applying Maxwell's equation for conduction through heterogeneous media. The results were compared with correlations, hard-field tomography data, and computational fluid dynamic simulations available in the literature, showing good agreement. This study thus demonstrates the capability of ERT using a linear probe to offer, besides qualitative tomographic images, reliable quantitative data regarding phase distribution in gas–liquid systems.     

Assessment of a Cylindrical and a Rectangular Plate Differential Mobility Analyzer for Size Fractionation of Nanoparticles at High-Aerosol Flow Rates

An existing differential mobility analyzer (DMA) of cylindrical electrodes and a novel DMA of rectangular plate electrodes are demonstrated for size fractionation of nanoparticles at high-aerosol flow rates in this work. The two DMAs are capable of delivering monodisperse size selected nanoparticles (SMPS σ_g < 1.1) at gas flow rates ranging from 200 slm to 500 slm. At an aerosol flow rate of 200 slm, the maximum attainable particle mean size is of about 20 nm for the cylindrical DMA and of nearly 50 nm for the rectangular plate DMA. The number concentration of the monodisperse nanoparticles delivered by the high-flow DMAs spans from 10⁴ cm^?3 to 10⁶ cm^?3 depending upon the particle mean size and particle size dispersion.

Copyright 2014 American Association for Aerosol Research     

N‐Benzyl‐4‐((heteroaryl)methyl)benzamides: A New Class of Direct NADH‐Dependent 2‐trans Enoyl–Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity

Isoniazid (INH) remains one of the cornerstones of antitubercular chemotherapy for drug‐sensitive strains of M. tuberculosis bacteria. However, the increasing prevalence of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains containing mutations in the KatG enzyme, which is responsible for the activation of INH into its antitubercular form, have rendered this drug of little or no use in many cases of drug‐resistant tuberculosis. Presented herein is a novel family of antitubercular direct NADH‐dependent 2‐trans enoyl–acyl carrier protein reductase (InhA) inhibitors based on an N‐benzyl‐4‐((heteroaryl)methyl)benzamide template; unlike INH, these do not require prior activation by KatG. Given their direct InhA target engagement, these compounds should be able to circumvent KatG‐related resistance in the clinic. The lead molecules were shown to be potent inhibitors of InhA and showed activity against M. tuberculosis bacteria. This new family of inhibitors was found to be chemically tractable, as exemplified by the facile synthesis of analogues and the establishment of structure–activity relationships. Furthermore, a co‐crystal structure of the initial hit with the enzyme is disclosed, providing valuable information toward the design of new InhA inhibitors for the treatment of MDR/XDR tuberculosis.     

Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.     

A comprehensive investigation of dye–chitosan blended films for green chemistry applications

In this paper, the ability of chitosan film to remove dyestuff from wastewater was evaluated for environmental applications, using three commercial direct azo dyes. Two chitosan films were adopted: the standard one prepared following a well‐known procedure to form it, and a novel one, with a weakly acidic character. Moreover, to improve the adsorption process, the hydrophobic character of the films was investigated. The pH of the dye solutions was also changed, showing an excellent ability in dye removal at pH 12. The films were characterized by means of spectroscopic and morphologic methods to better understand the nature of interactions between dyes and chitosan chains. Swelling ratio measurements were also performed. All analyses suggest that all dyes showed a strong affinity to chitosan polymer chains, with the presence of extended hydrogen bonds and Van der Waals forces perturbing the chitosan network. Interestingly, very good results were obtained in recycling experiments related to the dyeing capacities of chitosan blended films in the presence of textiles. An ecofriendly application is thus presented in this paper. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45945.     

Potential Effect of CD271 on Human Mesenchymal Stromal Cell Proliferation and Differentiation

The Low-Affinity Nerve Growth Factor Receptor (LNGFR), also known as CD271, is a member of the tumor necrosis factor receptor superfamily. The CD271 cell surface marker defines a subset of multipotential mesenchymal stromal cells and may be used to isolate and enrich cells derived from bone marrow aspirate. In this study, we compare the proliferative and differentiation potentials of CD271⁺ and CD271⁻ mesenchymal stromal cells. Mesenchymal stromal cells were isolated from bone marrow aspirate and adipose tissue by plastic adherence and positive selection. The proliferation and differentiation potentials of CD271⁺ and CD271⁻ mesenchymal stromal cells were assessed by inducing osteogenic, adipogenic and chondrogenic in vitro differentiation. Compared to CD271⁺, CD271⁻ mesenchymal stromal cells showed a lower proliferation rate and a decreased ability to give rise to osteocytes, adipocytes and chondrocytes. Furthermore, we observed that CD271⁺ mesenchymal stromal cells isolated from adipose tissue displayed a higher efficiency of proliferation and trilineage differentiation compared to CD271⁺ mesenchymal stromal cells isolated from bone marrow samples, although the CD271 expression levels were comparable. In conclusion, these data show that both the presence of CD271 antigen and the source of mesenchymal stromal cells represent important factors in determining the ability of the cells to proliferate and differentiate.     

Rosuvastatin Enhances the Catabolism of LDL apoB‐100 in Subjects with Combined Hyperlipidemia in a Dose Dependent Manner

Dose‐associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B‐100 in triacylglycerol rich lipoprotein (TRL, d < 1.019 g/ml) and low density lipoprotein (LDL) and of apoA‐I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB‐100 production rate (PR), as well as increase apoB‐100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB‐100 in TRL and LDL and apoA‐I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography‐mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 % (both P < 0.0001), triacylglycerol by 14 % (ns) and 35 % (P < 0.01), apoB by 30 and 36 % (both P < 0.0001), respectively, and had no significant effects on HDL cholesterol or apoA‐I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB‐100 FCR by 36 and 46 % (both ns) and LDL apoB‐100 by 63 and 102 % (both P < 0.05), respectively. HDL apoA‐I PR increased with low dose rosuvastatin (12 %, P < 0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB‐100 PR or HDL apoA‐I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB‐100, with no significant effects on apoB‐100 production or HDL apoA‐I kinetics.     

Rheological behavior and morphological and interfacial properties of PLA/TPE blends

Rheological and interfacial tension data were employed to predict the morphology and thermal and mechanical properties of noncompatibilized and compatibilized poly(lactic acid) (PLA)/thermoplastic elastomer (TPE) blends. PLA was melt blended with thermoplastic polyurethane (TPU) and ethylene elastomer (EE) and compatibilized by ethylene–butyl acrylate–glycidyl methacrylate (EBG) in an internal mixer chamber. Both TPU and EE TPEs have higher viscosities than PLA, and the interfacial properties evaluated have revealed better adhesion between domains of PLA–TPU. The efficiency of the compatibilizer agent EBG depended on the TPE type inferred by modifications in the scanning electron microscopy images of PLA/TPE blends and by the Izod impact strength (improved by 23%). The EBG was more effective in the PLA/TPU blend. The TPEs and EBG did not affect the PLA thermal stability, and no thermal event was observed in the usual PLA extrusion and injection temperature range. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47962.