The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, such as ondansetron, should be investigated in patients.

Folic acid supplementation appears to improve cognitive function and reduce blood levels of Aβ-related biomarkers in MCI. Larger-scale double-blind placebo-controlled randomized trials of longer duration are needed.

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PurposeObstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased risk for cardiovascular disease, diabetes, and other chronic conditions. Unfortunately, up to 90% of individuals with OSA remain without a diagnosis or therapy. We assess the relationship between OSA and blood biomarkers, and test the hypothesis that combinations of markers provide a characteristic OSA signature with diagnostic screening value. This validation study was conducted in an independent cohort in order to replicate findings from a prior feasibility study.Patients and methodsThis multicenter prospective study consecutively enrolled adult male subjects with clinically suspected OSA. All subjects underwent overnight sleep studies. An asymptomatic control group was also obtained. Five biomarkers were tested: glycated hemoglobin (HbA1c), C-reactive protein (CRP), uric acid, erythropoietin (EPO), and interleukin-6 (IL-6).ResultsThe study enrolled 264 subjects. The combination of HbA1c+CRP+EPO (area under the curve 0.78) was superior to the Epworth Sleepiness Scale (ESS; 0.53) and STOP-Bang (0.70) questionnaires. In non-obese subjects, the combination of biomarkers (0.75) was superior to body mass index (BMI; 0.61). Sensitivity and specificity results, respectively, were: HbA1c+CRP+EPO (81% and 60%), ESS (78% and 19%), STOP-Bang (75% and 52%), BMI (81% and 56%), and BMI in non-obese patients (81% and 38%).ConclusionWe verify our hypothesis and replicate our prior feasibility findings that OSA is associated with a characteristic signature cluster of biomarker changes in men. Concurrent elevations of HbA1c, CRP, and EPO levels should generate a high suspicion of OSA and may have utility as an OSA screening tool. Biomarker combinations correlate with OSA severity and, therefore, may assist sleep centers in identifying and triaging higher risk patients for sleep study diagnosis and treatment.

Glycyrrhizic acid (GA) and GA nanofibrils (GN) have been shown to be efficient natural emulsifiers for formation and stabilization of food emulsions. In this work, the emulsion properties of GN in the presence of soy protein isolate−pectin complex nanoparticles (SPNPs) were studied to understand the impact of the nanofibril−nanoparticle interactions on emulsion stabilization. In the presence of low GN concentrations (0.1−0.5 wt %), the synergy in reducing the interfacial tension was observed due to SPNPs−GN complexation in the bulk and at the interface by hydrogen bonding, endowing the prepared emulsions with an overall smaller droplet size. However, obvious flocculation and clustering of oil droplets occurred in these emulsions (especially at 0.25 and 0.5 wt % GN), which are probably induced by a depletion mechanism. At high GN concentrations (1−2 wt %), due to the preferential adsorption, the GN mainly dominated the interface and the subsequent formation and properties of emulsions. Accordingly, the self-standing emulsion gels were obtained, showing a small droplet size with d 32 of about 1.0−1.5 μm, homogeneous appearance and microstructure, and encouraging rheological properties including high gel strength, shear sensitivity, and good thixotropic recovery. This is mainly attributed to the formation of a fibrillar hydrogel network in the continuous phase as well as around the droplet surfaces.

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An enzymatic strategy was developed to generate asymmetrically branched N-glycans from natural sources by using a panel of glycosidases and glycosyltransferases. Briefly, LacZ β-galactosidase was employed to selectively trim symmetrically branched N-glycans isolated from bovine fetuin. The yielding stuctures were then converted to asymetrically branched core structures by robust glycosyltransferase for further extension.

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