Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.     

In Vivo Metabolic Responses to Different Formulations of Amino Acid Mixtures for the Treatment of Phenylketonuria (PKU)

Phenylketonuria (PKU) is a rare autosomal recessive inborn error of metabolism where the mainstay of treatment is a Phe restricted diet consisting of a combination of limited amounts of natural protein with supplementation of Phe-free or low-Phe protein substitutes and special low protein foods. Suboptimal outcomes may be related to the different absorption kinetics of free AAs, which have lower biological efficacy than natural proteins. Physiomimic Technology^TM is a technology engineered to prolong AA (AA-PT) release allowing physiological absorption and masking the odor and taste of free AAs. The aim of these studies was to assess the impact of AA-PT formulation on selected functional and metabolic parameters both in acute and long-term experimental studies. Adult rats in fasting conditions were randomized in different groups and treated by oral gavage. Acute AA-PT administration resulted in significantly lower BUN at 90 min versus baseline. Both BUN and glycemia were modulated in the same direction as intact casein protein. Long-term treatment with AA-PT significantly reduces the protein expression of the muscle degradation marker Bnip3L (−46%) while significantly increasing the proliferation of market myostatin (+58%). Animals dosed for 15 days with AA-PT had significantly stronger grip strength (+30%) versus baseline. In conclusion, the results suggest that the AA-PT formulation may have beneficial effects on both AA oxidation and catabolism with a direct impact on muscle as well as on other metabolic pathways.     

Chemically induced graft copolymerization of 4-vinyl pyridine onto carboxymethyl chitosan

A novel super absorbent polymer was prepared by graft copolymerization of 4-vinyl pyridine (4VP) onto the chains of carboxymethyl chitosan in aqueous solution using potassium persulphate (KPS) as initiator. The effect of monomer and initiator concentration, reaction temperature, and time on the grafting yield has been investigated. The maximum grafting yield was achieved at [KPS] = 4 × 10⁻² mol/L, [M] = 2.5 mol/L at reaction temperature = 60 °C within reaction time = 3 h. The molecular structure of the graft copolymer was confirmed by FTIR, surface morphology before and after the polymerization was examined by SEM. Different analyses were done for the graft copolymer such as X-ray diffraction, solubility tests, and thermal analysis. Different applications were done on the graft copolymer such as swell ability in different pH solutions, dye, and metal uptake.     

Synthesis,Characterization and Surface Activity of New Eco-friendly Schiff Bases Vanillin Derived Cationic Surfactants

Three eco-friendly cationic surface active agents were synthesized from the chemical modification of vanillin. The chemical structures of these surfactants were confirmed using elemental analysis, IR and NMR spectra. The surface activity measurements showed their high tendency towards adsorption and micellization and their good surface tension reduction, low interfacial tension. The emulsion stability measurements showed acceptable efficiency as emulsifying agents for short term emulsions. The biodegradability tests revealed that these compounds are eco-friendly and had completely degraded in 30 days.     

Preparation and characterization of chitosan films,crosslinked with symmetric aromatic dianhydrides to achieve enhanced thermal properties

This study has developed a new generation of crosslinked chitosan‐based films using symmetric aromatic dianhydrides as crosslinking agents. The formation of the dianhydride‐crosslinked chitosan hydrogel films was confirmed using Fourier transform infrared and solid‐state ¹³C NMR spectral analyses. The films obtained from these derivatives were characterized by their thermal, swelling and hydrophilic properties. The results showed that introducing a cyclic imide moiety into the chitosan matrices played a significant role in enhancing the thermal properties of these chitosan films. It was found that even at high levels of substitution, thermal stability of the studied chitosan derivatives was improved, in spite of a reduction in crystallinity. Heterocyclic imide linkages produced networks that were insoluble in both acidic and alkaline media but allowed swelling in aqueous media. An increase in the hydrophobicity of the chitosan film surfaces was observed after introduction of the cyclic imide moiety. These engineered films produced noteworthy results concerning their thermal and swelling properties. There is a need to further investigate these films for drug delivery and biomaterials applications. © 2014 Society of Chemical Industry     

Apron design for protecting double‐skin façade fires

Although double‐skin façade (DSF) is an environmental‐friendly architectural feature, its fire behaviour is a deep concern. The interior glass system including the glass pane, metal frame and associated accessories will be hotter than the exterior glass system as demonstrated by earlier studies. The glass pane above the fire room will be broken to spread flame into the upper compartment. Aprons are proposed to protect the air cavity of DSF in a way similar to those outside a single‐skin façade. In this paper, the effect of aprons in protecting against fire spread from an underlying compartment to the compartments above by preventing glass breakage of the inner glass pane was studied. Fire and smoke from a post‐flashover room fire adjacent to the DSF would be trapped in the air cavity between the two glass panes. Spreading of hot gases with different apron widths was studied by numerical simulations with CFD first. Fire environment with and without breaking the apron immediately above the fire room was studied. Full‐scale burning tests on part of an experimental DSF rig were then carried out to demonstrate the performance of horizontal apron in the DSF rig of 6 m tall and air cavity depth of 2 m with different apron widths. All demonstrated that providing apron is appropriate in protecting DSF fires. Copyright © 2014 John Wiley & Sons, Ltd.     

Effects of particulate matter on inflammatory markers in the general adult population

Background

Particulate air pollution is associated with increased risk of cardiovascular disease and stroke. Although the precise mechanisms underlying this association are still unclear, the induction of systemic inflammation following particle inhalation represents a plausible mechanistic pathway.

Methods

We used baseline data from the CoLaus Study including 6183 adult participants residing in Lausanne, Switzerland. We analyzed the association of short-term exposure to PM₁₀ (on the day of examination visit) with continuous circulating serum levels of high-sensitive C-reactive protein (hs-CRP), interleukin 1-beta (IL-1??), interleukin 6 (IL-6), and tumor-necrosis-factor alpha (TNF-??) by robust linear regressions, controlling for potential confounding factors and assessing effect modification.

Results

In adjusted analyses, for every 10???g/m³ elevation in PM₁₀, IL-1? increased by 0.034 (95?% confidence interval, 0.007-0.060) pg/mL, IL-6 by 0.036 (0.015-0.057) pg/mL, and TNF-?? by 0.024 (0.013-0.035) pg/mL, whereas no significant association was found with hs-CRP levels.

Conclusions

Short-term exposure to PM₁₀ was positively associated with higher levels of circulating IL-1?, IL-6 and TNF-?? in the adult general population. This positive association suggests a link between air pollution and cardiovascular risk, although further studies are needed to clarify the mechanistic pathway linking PM₁₀ to cardiovascular risk.     

Asymmetric Dimethylarginine Plasma Levels and Endothelial Function in Newly Diagnosed Type 2 Diabetic Patients

It is now well established that major risk factors for cardiovascular diseases (CVD) impact upon endothelial function by decreasing nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA), an endogenous analog of l-arginine, is able to inhibit the activity of endothelial-NO synthase, promoting endothelial dysfunction. Type 2 diabetes (T2D) is characterized by a reduced endothelium-dependent vasodilation and increased ADMA levels and ADMA is strongly associated with micro- and macrovascular diabetic complications. However, there are not a lot of data about the role of ADMA on endothelial function in newly diagnosed T2D patients without cardiovascular (CV) complications. For this aim, we have enrolled forty-five newly diagnosed T2D patients, evaluated by a oral glucose tolerance test, and thirty normal subjects. Endothelium-dependent and -independent vasodilatation was investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh) and sodium nitroprusside. ADMA was measured by high-performance liquid chromatography and insulin resistance (IR) by HOMA. Newly diagnosed T2D patients showed higher ADMA and l-arginine mean values in comparison with normal subjects and a significantly reduced ACh-stimulated forearm blood flow (FBF). In T2D patients FBF was significantly and inversely correlated with ADMA (r = −0.524, p < 0.0001) and in a multivariate regression analysis, ADMA resulted the stronger predictor of FBF, explaining the 27.5% of variability (p < 0.0001). In conclusion, ADMA was strongly related to endothelial dysfunction also in patients with newly diagnosed T2D, without clinically manifest vascular complications. This field is of great interest for understanding the mechanisms underlying the pathogenesis of diabetic disease and its CV complications.     

Does carbon nanopowder threaten amphibian development?

Lethal and teratogenic potentials of carbon nanoparticles (CNPs) in their amorphous form were investigated by the standardized Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a 96-h in vitro whole-embryo toxicity test based on the amphibian Xenopus laevis. Embryos were acutely exposed to 1, 10, 100 and 500 mg/L CNP suspensions and evaluated for lethality, malformations and growth inhibition. Larvae were processed for histological and ultrastructural analyses to detect the main affected organs, to look for specific lesions at the subcellular level and to image and track CNPs into tissues. Only the highest CNP suspension resulted in being embryolethal for X. laevis larvae, while malformed larva percentages significantly differed from controls starting from 100 mg/L. The stomach and gut were the preferential CNP accumulation sites, on the contrary, the digestive epithelium remained intact. The analyses showed the presence of isolated nanoparticles and/or aggregates in different secondary target organs. CNPs were found in circulating erythrocytes. The research confirms the good tolerance of X. laevis towards pure elemental carbon in its nanoparticulate amorphous form, but highlights the possibility of CNP transfer toward all body areas.