Effects of high glucose on vascular endothelial growth factor synthesis and secretion in aortic vascular smooth muscle cells from obese and lean zucker rats

Type 1 diabetes is characterized by insulin deficiency, type 2 by both insulin deficiency and insulin resistance: in both conditions, hyperglycaemia is accompanied by an increased cardiovascular risk, due to increased atherosclerotic plaque formation/instabilization and impaired collateral vessel formation. An important factor in these phenomena is the Vascular Endothelial Growth Factor (VEGF), a molecule produced also by Vascular Smooth Muscle Cells (VSMC). We aimed at evaluating the role of high glucose on VEGF-A(164) synthesis and secretion in VSMC from lean insulin-sensitive and obese insulin-resistant Zucker rats (LZR and OZR). In cultured aortic VSMC from LZR and OZR incubated for 24 h with d-glucose (5.5, 15 and 25 mM) or with the osmotic controls l-glucose and mannitol, we measured VEGF-A(164) synthesis (western, blotting) and secretion (western blotting and ELISA). We observed that: (i) d-glucose dose-dependently increases VEGF-A(164) synthesis and secretion in VSMC from LZR and OZR (n = 6, ANOVA p = 0.002-0.0001); (ii) all the effects of 15 and 25 mM d-glucose are attenuated in VSMC from OZR vs. LZR (p = 0.0001); (iii) l-glucose and mannitol reproduce the VEGF-A(164) modulation induced by d-glucose in VSMC from both LZR and OZR. Thus, glucose increases via an osmotic mechanism VEGF synthesis and secretion in VSMC, an effect attenuated in the presence of insulin resistance.     

Synthesis, biological activity, and ADME properties of novel S-DABOs/N-DABOs as HIV reverse transcriptase inhibitors

Previous studies aimed at exploring the SAR of C2-functionalized S-DABOs demonstrated that the substituent at this position plays a key role in the inhibition of both wild-type RT and drug-resistant enzymes, particularly the K103N mutant form. The introduction of a cyclopropyl group led us to the discovery of a potent inhibitor with picomolar activity against wild-type RT and nanomolar activity against many key mutant forms such as K103N. Despite its excellent antiviral profile, this compound suffers from a suboptimal ADME profile typical of many S-DABO analogues, but it could, however, represent a promising candidate as an anti-HIV microbicide. In the present work, a new series of S-DABO/N-DABO derivatives were synthesized to obtain additional SAR information on the C2-position and in particular to improve ADME properties while maintaining a good activity profile against HIV-1 RT. In vitro ADME properties (PAMPA permeation, water solubility, and metabolic stability) were also experimentally evaluated for the most interesting compounds to obtain a reliable indication of their plasma levels after oral administration.     

Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review

Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.     

Modulation of Aβ42 Aggregation Kinetics and Pathway by Low-Molecular-Weight Inhibitors

The aggregation of amyloid-β 42 (Aβ42) is directly related to the pathogenesis of Alzheimer's disease. Here, we have investigated the early stages of the aggregation process, during which most of the cytotoxic species are formed. Aβ42 aggregation kinetics, characterized by the quantification of Aβ42 monomer consumption, were tracked by real-time solution NMR spectroscopy (RT-NMR) allowing the impact that low-molecular-weight (LMW) inhibitors and modulators exert on the aggregation process to be analysed. Distinct differences in the Aβ42 kinetic profiles were apparent and were further investigated kinetically and structurally by using thioflavin T (ThT) and transmission electron microscopy (TEM), respectively. LMW inhibitors were shown to have a differential impact on early-state aggregation. Insight provided here could direct future therapeutic design based on kinetic profiling of the process of fibril formation.     

A new three-parameter Corresponding States Model for pure Halocarbons Viscosity Prediction

Predictive and semipredictive models for viscosity calculation are currently needed and highly appreciated. Models developed for halogenated refrigerants (HR) and based on Corresponding States (CS) are leading to a prediction accuracy comparable to that of specifically developed models. In the present work, using recently published, highly accurate viscosity dedicated equations, it has been verified that viscosity conforms to a two-parameter CS model is then developed, based on Teja and coworker's three-parameter CS structure. Two fluids of the same family are taken for reference, and the reduced viscosity of a third fluid is obtained in reduced P,T variables. At first the Pitzer acentric factor is proposed as a third parameter, then it is substituted with a temperature-dependent function fitted on saturated viscosity data. The prediction accuracy of the model is comparable to that of the reference fluid equations and, considering its predictive nature, it is a satisfactory tool for the needs of technical applications.     

Synthesis,characterization, and degradation of block polyesteramides containing poly(L-lactide) segments

Random multiblock polyesteramides (PEAs) having polyester (PE) content of 20–50 wt % have been prepared by low-temperature polycondensation using sebacoyl chloride, 1,6-diaminohexane, and telechelic oligomers of L-lactide with M_n = 600–1500. The PEAs were characterized by IR and ¹H-NMR spectroscopy, wide-angle X-ray diffraction, and thermal analysis. Only the polyamide segments are able to crystallize, and the crystallinity depends on the composition and architecture of the PEAs. From viscosity and IR measurements it was established that the chain degradation of PEA powders or films suspended in buffer solutions occurs by hydrolysis of the ester linkages. The degradation rate is influenced by pH, PE content, and, to a lesser extent, by crystallinity. © 1992 John Wiley & Sons, Inc.     

Heat Induced Structure Modifications in Polymer‐Layered Silicate Nanocomposites

Summary: The success of the use of layered silicates in polymer nanocomposites, to improve physical and chemical properties is strictly related to a deeper knowledge of the mechanistic aspects on which the final features are grounded. This work shows the temperature induced structural rearrangements of nanocomposites based on poly[ethylene‐co‐(vinyl acetate)] (EVA) intercalated‐organomodified clay (at 3–30 wt.‐% silicate addition) which occur in the range between 75 and 350 °C. In situ high temperature X‐ray diffraction (HT‐XRD) studies have been performed under both nitrogen and air to monitor the modifications of the nanocomposite structure at increasing temperatures under inert/oxidative atmosphere. Heating between 75 and 225 °C, under nitrogen or air, causes the layered silicate to migrate towards the nanocomposite surface and to increase its interlayer distance. The degradation of both the clay organomodifier and the VA units of the EVA polymer seems to play a key role in driving the evolution of the silicate phase in the low temperature range. The structural modifications of the nanocomposites in the high temperature range (250–350 °C), depended on the atmosphere, either inert or oxidizing, in which the samples were heated. Heating under nitrogen led to deintercalation and thus a decrease of the silicate interlayer space, whereas exfoliation was the main process under air leading to an increase of the silicate interlayer space.

Heat induced structural modification of EVA‐clay nanocomposite under nitrogen and air.     

Solar barometric distillation for seawater desalting part I: Basic layout and operational/technical features

The report presents an innovative solar barometric distillation technology for seawater desalting (SW-SBD) which has several attractive features such as: (1) efficient vacuum solar collectors of simple construction; (2) a barometric layout for quasi-steady operation at subatmospheric pressure; (3) a demister system of simple mechanical construction; and (4) an electronic control system regulating plant productivity parameters on available solar radiation flux. The proposed seawater desalting technology consists of single-effect distillation with water vapor produced and heated at subatmospheric pressure in a solar collector loop; the basic layout, operational features, and energy efficiency are presented and analysed in detail. Subsequent reports will provide technico-economical data from prototype desalting plants in view of industrial implementation. A promising specific electric energy consumption,∼2 kWm³ offresh water produced, was found by estimating pumping power requirements of major SW-SBD plant pumps. A sizable reduction in produced water cost with respect to an existing solar seawater desalting plant in Abu Dhabi is expected on the basis of a preliminary economic evaluation for a ∼100 m³/d plant prototype.