Poly(butylene succinate‐co‐butylene adipate)/polyethylene oxide blends for controlled release materials: A morphological study

Varying the formulation and processing conditions of polymer blends allows the design of materials with a large range of morphologies. Active materials embedding active compounds in a devoted phase are promising applications of such blends, offering possible various transport properties. In this study, 13 poly(butylene succinate‐co‐butylene adipate) (PBSA)/polyethylene oxide (PEO) blends were extruded in a slit die. Their morphologies were characterized by water extraction (selective PEO dissolution), FTIR spectroscopy, and differential scanning calorimetry. Transport properties were assessed by water vapor permeation and fluorescein release as model migrant. Indeed, the desorption in water of fluorescein (previously entrapped in PEO) was monitored to preliminary investigate the release properties of these materials: two morphologies were obtained (i) pseudo multilayer films made of PEO‐rich layer/PBSA‐rich layer/PEO‐rich layer and (ii) PEO nodules dispersed in the PBSA‐rich matrix for the highest PBSA contents. The first systems were erodible ones with an uncontrolled fast delivery by PEO dissolution whereas the second ones showed a controlled release by permeation through the PBSA matrix from PEO nodules. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42874.     

APOB CRISPR-Cas9 Engineering in Hypobetalipoproteinemia: A Promising Tool for Functional Studies of Novel Variants

Hypobetalipoproteinemia is characterized by LDL-cholesterol and apolipoprotein B (apoB) plasma levels below the fifth percentile for age and sex. Familial hypobetalipoproteinemia (FHBL) is mostly caused by premature termination codons in the APOB gene, a condition associated with fatty liver and steatohepatitis. Nevertheless, many families with a FHBL phenotype carry APOB missense variants of uncertain significance (VUS). We here aimed to develop a proof-of-principle experiment to assess the pathogenicity of VUS using the genome editing of human liver cells. We identified a novel heterozygous APOB-VUS (p.Leu351Arg), in a FHBL family. We generated APOB knock-out (KO) and APOB-p.Leu351Arg knock-in Huh7 cells using CRISPR-Cas9 technology and studied the APOB expression, synthesis and secretion by digital droplet PCR and ELISA quantification. The APOB expression was decreased by 70% in the heterozygous APOB-KO cells and almost abolished in the homozygous-KO cells, with a consistent decrease in apoB production and secretion. The APOB-p.Leu351Arg homozygous cells presented with a 40% decreased APOB expression and undetectable apoB levels in cellular extracts and supernatant. Thus, the p.Leu351Arg affected the apoB secretion, which led us to classify this new variant as likely pathogenic and to set up a hepatic follow-up in this family. Therefore, the functional assessment of APOB-missense variants, using gene-editing technologies, will lead to improvements in the molecular diagnosis of FHBL and the personalized follow-up of these patients.     

Experimental investigation in the TOSQAN facility of heat and mass transfers in a spray for containment application

TOSQAN is an experimental program undertaken by the Institut de Radioprotection et de Sûreté Nucléaire (IRSN) in order to perform thermal hydraulic containment studies. The TOSQAN facility is a large enclosure devoted to simulate typical accidental thermal hydraulic flow conditions in nuclear-pressurized water reactor (PWR) containment. The TOSQAN facility which is highly instrumented with non-intrusive optical diagnostics is particularly adapted to nuclear safety CFD code validation. The present work is devoted to studying the interaction of a water spray injection used as a mitigation means in order to reduce the gas pressure and temperature in the containment, to produce gases mixing and washout of fission products. In order to have a better understanding of heat and mass transfers between spray droplets and the gas mixture, and to analyze mixing effects due to spray activation, we perform detailed characterization of the two-phase flow.     

Non-Catalyzed and Pt/γ-Al2O3 Catalyzed Hydrothermal Cellulose Dissolution-Conversion: Influence of the Reaction Parameters

The dissolution of cellulose under 5 MPa of H₂ in the absence of catalyst is temperature and time dependant. The presence of Pt/γ-Al₂O₃ increases the initial rate of dissolution. The presence of H₂/Pt is essential although its exact role has not been well elucidated.     

Assisted Tandem Palladium(II)/Palladium(0)‐Catalyzed C‐ and N‐Arylations of Quinoxalin‐2(1 H)‐ones in Water

A straightforward assisted tandem palladium(II)‐ and palladium(0)‐catalyzed direct C‐3 and N‐4 arylation of quinoxalin‐2(1 H)‐ones with boronic acids and aryl halides in water as safe and cheap solvent is reported. This environmentally friendly catalytic protocol is compatible with a wide range of functional groups and allows construction of various biologically important quinoxalin‐2(1 H)‐one backbones.

     

Phenolic acids composition and antioxidant activity of canola extracts in cooked beef,chicken and pork

Crude polyphenol extracts (15 or 100 mg gallic acid equivalents (GAE)/kg meat) from canola meal reduced the formation of 2-thiobarbituric acid-reactive substances (TBARS) in pre-cooked beef (66–92%), pork (43–75%) and chicken (36–70%). The canola extract contained sinapic (99.7%), ferulic (0.28%) and p-hydroxybenzoic acids (0.07%).     

Gestational and lactational exposure to dichlorinated bisphenol A induces early alterations of hepatic lipid composition in mice

Objective

Using non-invasive magnetic resonance (MR) techniques and a histological approach, we assessed the outcomes of perinatal exposure at a low dose of 3,3′-DCBPA (2-chloro-4-[1-(3-chloro-4-hydroxyphenyl)-1-methylethyl]phenol) and/or 3,5-DCBPA (2,6-dichloro-4-[1-(4-hydroxyphenyl)-1-methylethyl]phenol) on mice livers.

Materials and methods

Fertilized female Swiss mice were injected intraperitoneally during gestation and lactation with either vehicle control, 20 μg/kg/day of BPA, 3,5-DCBPA, 3,3′-DCBPA or a mixture (mix-DCBPA). Complementary methods were used to evaluate, in male and female pups, (1) liver structure by texture analysis of images obtained through MR imaging (MRI) and histology, (2) hepatic lipid composition through in vivo ¹H MR spectroscopy (¹H MRS).

Results

Principal component analysis of texture parameters showed no structural modification of the liver with BPA and DCBPA treatments. Accordingly, no hepatic microvesicular steatosis was observed through hematoxylin–eosin staining. Compared to control, MRS revealed no difference in lipid composition for BPA, 3,5-DCBPA or 3,3′-DCBPA groups. However, MRS detected a significant increase in the mix-DCBPA groups for the saturated component of fatty acids (FA), total unsaturated FA bond index and polyunsaturated FA bond index.

Conclusion

Prior to any structural changes, polyunsaturated fatty acids significantly increased in young male and female mice exposed perinatally at a low dose to a mixture of dichlorinated BPA.

     

How to increase the safety and efficacy of compounds against neurodegeneration? A multifunctional approach

Successful drug design requires not only the detailed knowledge of the pharmacokinetic and pharmacodynamic profiles of the drug candidate portfolio but also a thorough documentation of the possible toxic effects on humans and the environment. Thus, experimental and computational strategies able to measure or predict specific profiles of designed compounds related to their potential toxicity are highly desired. Moreover, a strategy to avoid toxic effects thus enhancing the potential efficacy of drug candidates is of great interest. To fulfil this aim, the pharmacochemistry research unit at the EPGL has recently developed and improved methodologies that detect the potential human health and environmental hazards of compounds active against neurodegeneration at an early stage. A three-step strategy is presented herein. In particular, i) an alternative index to model the bioconcentration of chemicals in the environment was determined; ii) the antioxidant activity of chemical species against free radicals was evaluated. Moreover, since antioxidants play a key role in both toxicity prevention and neuroprotection, iii) the potential interaction of such compounds with enzymatic targets involved in the neurodegenerative cascade was investigated in silico.