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A method that can rapidly and effectively capture and separate pathogenic bacteria, which remain viable even after capture for subsequent analysis, is potential future tool for medicine, water and food safety. In this study, novel antimicrobial peptide-based magnetic nanoparticles with neutralized bactericidal effects are developed for rapid and efficient capture and removal of pathogenic bacteria in water samples. The antimicrobial peptide-functionalized magnetic nanoparticles (AMP-MNPs) consist of magnetic core (Fe3O4), polydopamine (PDA) as an intermediate layer and antimicrobial peptide (Magainin I) as an outer layer (PDA@Fe3O4-AMP). The unique structure of AMP-MNPs allows retaining their capture ability via strong electrostatic interactions, while eliminating their bactericidal actions during interactions with bacteria’s outer membrane. The results of fluorescent microscopy indicate that the AMP-MNPs has no bactericidal effect, but only the binding ability towards bacteria. Factors such as concentration of AMP-MNPs, pH of the medium and ionic strength are crucial in mediating rapid and efficient bacterial capture. Higher concentration of AMP-MNPs (0.5 mg/mL) results in a high sensitive capture effect on 5 × 106–5 × 101 cfu/mL E. coli O157:H7, and a broad spectrum of capture ability towards various bacterial strains (1.5 × 107 cfu/mL) and allow rapid and efficient capture and magnetic-separation of pathogenic bacteria from tap and recreational water samples with capture efficiency greater than 97% and incubation time as short as 5 s. Whereas semi-selective capture of pathogenic and Gram-negative bacteria is achieved at lower concentration of AMP-MNPs (0.1 mg/mL). The developed AMP-MNPs may find great potential in microbiological applications and water quality analyses.

Objective Adipocytes are robust protein secretors, most notably of adipokines, hormone-like polypeptides, which act in an endocrine and paracrine fashion to affect numerous physiological processes such as energy balance and insulin sensitivity. To understand how such proteins are assembled for secretion we describe the function of a novel endoplasmic reticulum oxidoreductase, adiporedoxin (Adrx). Methods Adrx knockdown and overexpressing 3T3-L1 murine adipocyte cell lines and a knockout mouse model were used to assess the influence of Adrx on secreted proteins as well as the redox state of ER resident chaperones. The metabolic phenotypes of Adrx null mice were characterized and compared to WT mice. The correlation of Adrx levels BMI, adiponectin levels, and other inflammatory markers from adipose tissue of human subjects was also studied. Results Adiporedoxin functions via a CXXC active site, and is upstream of protein disulfide isomerase whose direct function is disulfide bond formation, and ultimately protein secretion. Over and under expression of Adrx in vitro enhances and reduces, respectively, the secretion of the disulfide-bonded proteins including adiponectin and collagen isoforms. On a chow diet, Adrx null mice have normal body weights, and glucose tolerance, are moderately hyperinsulinemic, have reduced levels of circulating adiponectin and are virtually free of adipocyte fibrosis resulting in a complex phenotype tending towards insulin resistance. Adrx protein levels in human adipose tissue correlate positively with adiponectin levels and negatively with the inflammatory marker phospho-Jun kinase. Conclusion These data support the notion that Adrx plays a critical role in adipocyte biology and in the regulation of mouse and human metabolism via its modulation of adipocyte protein secretion., Graphical abstract, Highlights • Adrx is an adipocyte specific, endoplasmic reticulum oxidoreductase upstream of disulfide bond formation. • Adrx over and under expression in vitro results enhanced and decreased protein secretion, respectively. • Mice lacking Adrx have lower levels of circulating adiponectin and decreased fibrosis. • Adrx is expressed in human adipocytes and down regulated in proportion to the level of inflammation.

TAK-559, a newly developed non-thiazolidinedione, activates both peroxisome proliferator-activated receptors alpha and gamma. We investigated the effects of TAK-559 on dyslipidemia and insulin resistance in nonhuman primates. Five adult male obese prediabetic rhesus monkeys were studied on vehicle and after TAK-559 treatment (0.3, 1.0, 3.0 mg/kg per day) for a total of 12 weeks. No significant changes were observed in body weight and fasting plasma glucose, total plasma cholesterol, very low-density lipoprotein-triglyceride, and low-density lipoprotein cholesterol levels. TAK-559 treatment resulted in significant elevation of circulating high-density lipoprotein (HDL) cholesterol levels, consisting of an increase in large HDL particles and a decrease in small dense HDL particles. Nuclear magnetic resonance data exhibited a less atherogenic lipoprotein profile with treatment. Plasma triglyceride and apolipoprotein B-100 levels decreased, whereas apolipoprotein A-I increased during TAK-559 treatment. Hyperinsulinemia and insulin resistance (quantitative insulin sensitivity check index and homeostasis model assessment) were significantly corrected with the highest dose of 3.0 mg/kg per day in these prediabetic monkeys. In addition, no adverse effects on representative liver function parameters were observed during the study period. These results suggest that TAK-559 had beneficial effects on lipoprotein profiles and insulin sensitivity, without any side effect on body weight, which suggests that TAK-559 may provide a potentially safe approach for delaying the onset of type 2 diabetes mellitus and may reduce the risk of cardiovascular disease. The positive effects of TAK-559 in nonhuman primates have led to further clinical trials of TAK-559 in Europe and the United States.