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.     

The role of K2O on sintering and crystallization of glass powder compacts in the Li2O–K2O–Al2O3–SiO2 system

The effects of K₂O content on sintering and crystallization of glass powder compacts in the Li₂O–K₂O–Al₂O₃–SiO₂ system were investigated. Glasses featuring SiO₂/Li₂O molar ratios of 2.69–3.13, far beyond the lithium disilicate (LD-Li₂Si₂O₅) stoichiometry, were produced by conventional melt-quenching technique. The sintering and crystallization behaviour of glass powders was explored using hot stage microscopy (HSM), scanning electron microscopy (SEM), differential thermal (DTA) and X-ray diffraction (XRD) analyses. Increasing K₂O content at the expense of SiO₂ was shown to lower the temperature of maximum shrinkage, eventually resulting in early densification of the glass-powder compacts. Lithium metasilicate was the main crystalline phase formed upon heat treating the glass powders with higher amounts of K₂O. In contrast, lithium disilicate predominantly crystallized from the compositions with lower K₂O contents resulting in strong glass–ceramics with high chemical and electrical resistance. The total content of K₂O should be kept below 4.63 mol% for obtaining LD-based glass–ceramics.     

Modeling and simulation of the phase‐inversion process during membrane preparation

The objective of this work is to present a simple mathematical model to describe the main features of phase inversion by immersion precipitation. The model was developed for planar geometry and is used to simulate membrane synthesis. Two systems commonly used for membrane preparation were used for simulations: cellulose acetate/acetone/water and polyetherimide/N‐methylpyrrolidone/water. The influence of nonsolvent addition to initial polymer casting solutions, solvent addition to the coagulation bath, and geometric variables, such as polymer film thickness, on the final precipitation conditions were studied through simulation and compared to available experimental data. The results are in good agreement with published results. 1 - 3 It is shown that polymer film composition profiles at the moment of precipitation may give important information about the structure and substructure of formed membrane. It is also shown, for both polymeric systems investigated in this work, that the dynamics of the mass transfer process seems to be much more important than the influence of the concentration on the diffusion and thermodynamic partition coefficients, as fair agreement with available experimental data was obtained even when these coefficients were assumed to be constant. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 3036–3051, 2001     

Fluidized‐bed reactor modeling for polyethylene production

Gas‐phase technology for polyethylene production has been widely used by industries around the world. A good model for the reactor fluid dynamics is essential to properly set the operating conditions of the fluidized‐bed reactor. The fluidized‐bed model developed in this work is based on a steady‐state model, incorporating interactions between separate bubble, emulsion gas phase, and emulsion solid polymer particles. The model is capable not only of computing temperature and concentration gradients for bubble and emulsion phases, calculating polymer particle mean diameter throughout the bed and polyethylene production rate, but also of pinpointing the appearance of hot spots and polymer meltdown. The model differs from conventional well‐mixed fluidized‐bed models by assuming that the particles segregate within the bed according to size and weight differences. The model was validated using literature and patent data, presenting good representation of the behavior of the fluidized‐bed reactor used in ethylene polymerization. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 321–332, 2001     

Synthesis of polar vinyl monomer–olefin copolymers by α‐diimine nickel catalyst

Vinyl acetate, methyl methacrylate, acrylonitrile and methyl vinyl ketone were investigated for co‐ and terpolymerization with ethylene and ethylene–propylene. Precursor [bis(N,N ′‐dimesitylimino)acenaphthene]dibromonickel, activated by methylaluminoxane was used as a catalyst system and trialkylaluminium was employed to block the polar groups for these polymerizations. Polymerization activities of the order of magnitude of 10⁶ in the case of vinyl acetate and methyl methacrylate, and 10⁵ in the case of acrylonitrile were achieved. Microanalysis and GPC of acrylonitrile copolymers found about 17 units of acrylonitrile per polymer chain. Copolymers with very different properties from the parent homopolymers were obtained in all cases except that of methyl vinyl ketone. © 2001 Society of Chemical Industry     

Electrospinning of gelatin fibers using solutions with low acetic acid concentration: Effect of solvent composition on both diameter of electrospun fibers and cytotoxicity

Gelatin fibers were prepared by electrospinning of gelatin/acetic acid/water ternary mixtures with the aim of studying the feasibility of fabricating gelatin nanofiber mats at room temperature using an alternative benign solvent by significantly reducing the acetic acid concentration. The results showed that gelatin nanofibers can be optimally electrospun with low acetic acid concentration (25%, v/v) combined with gelatin concentrations higher than 300 mg/mL. Both gelatin solutions and electrospun gelatin mats (prepared with different acetic acid aqueous solutions) were analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry techniques to determine the chemical and structural changes of the polymer. The electrospun gelatin mats fabricated from solutions with low acetic acid content showed some advantages as the maintenance of the decomposition temperature of the pure gelatin (～ 230°C) and the reduction of the acid content on electrospun mats, which allowed to reach a cell viability upper than 90% (analyzed by cell viability test using human dermal fibroblast and embryonic kidney cells). This study has also analyzed the influence of gelatin and acetic acid concentration both on the solution viscosity and the electrospun fiber diameter, obtaining a clear relationship between these parameters. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42115.     

Metformin Reduces Lipogenesis Markers in Obese Mice Fed a Low-Carbohydrate and High-Fat Diet

Lipogenesis is the process by which fatty acids are synthesized. In metabolic syndrome, an insulin resistant state along with high plasma levels of free fatty acids (FFA) and hyperglycemia may contribute to the lipogenic process. The aim of the present study was to investigate the effects of oral administration of metformin on the expression of lipogenic genes and glycemic profile in mice fed with low‐carbohydrate high‐fat diet by evaluating their metabolic profile. SWISS male mice were divided into 4 groups (N = 7) that were fed with standard (ST), standard plus metformin (ST + MET), low‐carbohydrate high‐fat diet (LCHFD) and low‐carbohydrate high‐fat diet plus metformin (LCHFD + MET) (100 mg kg^?1 diet) diets respectively. Food intake, body weight and blood parameters, such as glucose tolerance, insulin sensitivity, glucose, HDL‐c, total cholesterol, triglycerides, ASL and ALT levels were assessed. Histological analyses were performed on hematoxylin and eosin‐stained epididymal adipose tissue histological specimens. The expression levels of peroxisome proliferator‐activated receptor (PPARγ), sterol regulatory element‐binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl‐CoA carboxylase (ACC), were assessed by RT‐PCR. This study showed that metformin decreased adipocyte area, body weight and food consumption in obese animals when compared to the standard group. Furthermore, the expression of lipogenic markers in adipose tissue were diminished in obese animals treated with metformin. This data showed that oral administration of metformin improved glucose and lipid metabolic parameters in white adipose tissue by reducing the expression of lipogenesis markers, suggesting an important clinical application of MET in treating obesity‐related diseases in metabolic syndrome.     

A Quinacrine Analogue Selective Against Gastric Cancer Cells: Insight from Biochemical and Biophysical Studies

One of the earliest synthetic antimalarial drugs, quinacrine, was recently reported as interesting for the treatment of acute myeloid leukemia. Inspired by this and similar findings, we evaluated a set of quinacrine analogues against gastric (MKN‐28), colon (Caco‐2), and breast (MFC‐7) cancer cell lines and one normal human fibroblast cell line (HFF‐1). All the compounds, previously developed by us as dual‐stage antimalarial leads, displayed antiproliferative activity, and one of the set stood out as selective toward the gastric cancer cell line, MKN‐28. Interestingly, this compound was transported across an in vitro MKN‐28 model cell line in low amounts, and approximately 80 % was trapped inside those cells. Nuclear targeting of the same compound and its interactions with calf thymus DNA were assessed through combined fluorescence microscopy, spectroscopy, and calorimetry studies, which provided evidence for the compound's ability to reach the nucleus and to interact with DNA.