The Role of Anti-Inflammatory Adipokines in Cardiometabolic Disorders: Moving beyond Adiponectin

The global burden of obesity has multiplied owing to its rapidly growing prevalence and obesity-related morbidity and mortality. In addition to the classic role of depositing extra energy, adipose tissue actively interferes with the metabolic balance by means of secreting bioactive compounds called adipokines. While most adipokines give rise to inflammatory conditions, the others with anti-inflammatory properties have been the novel focus of attention for the amelioration of cardiometabolic complications. This review compiles the current evidence on the roles of anti-inflammatory adipokines, namely, adiponectin, vaspin, the C1q/TNF-related protein (CTRP) family, secreted frizzled-related protein 5 (SFRP5), and omentin-1 on cardiometabolic health. Further investigations on the mechanism of action and prospective human trials may pave the way to their clinical application as innovative biomarkers and therapeutic targets for cardiovascular and metabolic disorders.     

Maximizing polymer livingness in nitroxide-mediated miniemulsion polymerizations

Recent efforts to adapt nitroxide-mediated living radical polymerization chemistry to colloidal systems have shown considerable progress when miniemulsions are used. Miniemulsion SFRP in fact can yield higher conversions (>99%) and faster reaction rates than bulk SFRP. Much of the advantage of operating in miniemulsion arises from the inherent advantages of having a two phase system, in which the aqueous phase can be employed as a medium to introduce rate enhancing additives such as ascorbic acid to the reaction loci with a high degree of control. Additives such as ascorbic acid act by consuming excess nitroxide, and therefore directly influence the rate. Results on the effect of ascorbic addition on rate, molecular weight and livingness are presented. We have also begun to address the issue of high operating temperatures in TEMPO-mediated SFRP (∼120-135 °C) that require a pressurized reactor. We have run experiments using TEMPO at 100 °C with slowly decomposing initiator added to maintain an appropriate free nitroxide concentration. Reasonable reaction rates are obtained, albeit with higher polydispersities (∼1.6). Challenges and opportunities related to lower temperature operation are discussed.     

Application of micromechanical models for elasticity and failure to short fibre reinforced composites. Numerical implementation and experimental validation

This paper deals with numerical modelling of the mechanical behaviour of short fibre reinforced plastic composites manufactured by the injection moulding process.First of all, an experimental program has been carried out in which the local fibre orientation distribution has been measured in an 80 × 80 × 2 mm injected plate by means of polished cut sections, analysed with SEM and image processing software. Tensile and three-point bending tests have been performed to obtain the elastic and strength response of the material in different locations along the plate and at two directions (parallel and normal to the flow direction).Analytical micromechanical models and averaging procedures have been implemented to relate the local fibre orientation distribution with the effective local anisotropic response of the material (elastic and strength). The models are validated by means of the finite element simulation of the performed characterisation tests.Finally, the methodology is applied to an injection moulded component with complex geometry. Fibre orientation data predicted with mould-flow software has been used to determine the local effective elastic stiffness and strength coefficients. A FE simulation of the functional behaviour of the component has been carried out. Results indicate that the proposed variable stiffness/strength anisotropic model predicts a lower load for onset of failure than when applying an equivalent isotropic material model.     

Nitroxide‐Controlled Grafting by an Insertion Mechanism using a Polymerizable N‐Oxyl

Summary: The polymerizable nitroxide 4‐acryloyloxy‐2,2,6,6‐tetramethylpiperidine‐N‐oxyl (AOTEMPO) was utilized in a two step polymerization to prepare alkoxyamine‐functionalized backbone polymers. These backbones were then used as initiators for stable free‐radical graft polymerizations in bulk at 125 °C. The products were cleaved into their linear components by reaction with L ‐(+)‐ascorbic acid allowing a reproducible analysis of the molecular weights. The influences of the backbone concentration and the graft density on the polymerization were investigated. Graft polymers purely consisting of styrene were produced as well as polymers with a backbone based on 2‐ethoxyethyl acrylate (EOEA). In addition a graft polymer with block copolymer side chains was prepared by extending a preformed graft polymer. In all cases the controlled course of the reaction was confirmed by the linear increase of the molecular weights over conversion and the low polydispersities of the products.

Structure of an extended graft copolymer.     

Deregulation of Secreted Frizzled-Related Protein 5 in Nonalcoholic Fatty Liver Disease Associated with Obesity

Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage.