Jernigankondrup4091

To assess bioequivalence of a generic dabigatran etexilate capsule in healthy Chinese subjects under fasting and fed conditions. This was an open-label, single-center, randomized four-period crossover study with a 7-day washout period. A single oral dose of 150 mg generic dabigatran etexilate capsule (test drug) or a commercial dabigatran etexilate capsule (Pradaxa® , reference drug) was given to healthy volunteers under the fasting and fed conditions. Plasma concentrations of total and free dabigatran were detected using a validated HPLC-MS/MS method. A noncompartmental method was used for pharmacokinetic analysis and established coagulation assays were applied for pharmacodynamic analysis. The 90% CIs of the test/reference ratios of Cmax , AUC0-t , and AUC0-∞ for the total dabigatran concentration were 92.57%-106.58%, 91.63%-106.32%, and 92.54%-106.17%, respectively, under fasting condition, and 99.30%-110.74%, 98.58%-105.37%, and 97.75%-103.99%, respectively, under fed conditions. The 90% CIs of the ratios of the parameters for the free dabigatran were 93.18%-106.98%, 92.13%-107.10%, 92.89%-106.48%, respectively, under fasting condition, and 100.05%-110.89%, 99.37%-106.23%, 97.59%-103.98%, respectively, under the fed condition. Additionally, the upper limit of the 90% CIs for σWT/σWR was below 2.5. There were no significant differences in the coagulation parameters including thrombin clotting time, activated partial thromboplastin time, and anti-IIa activity between the two preparations. The generic dabigatran etexilate capsule is bioequivalent to the brand-named product in healthy Chinese volunteers under fasting and fed conditions. The two products have comparable pharmacodynamic parameters, with a good safety profile. In addition, food intake influences absorption of both products in a similar way. © 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.Current scaffolds applied for bone tissue engineering are still lacking sufficient osteogenic capacity to induce efficient bone regeneration. Biodegradable microsphere-type scaffolds are designed to achieve the dual-controlled release of a Chinese medicine (i.e., icariin, ICA) and a bioactive ion (i.e., Mg2+ ), in order to achieve their synergistic effect on inducing osteogenesis. The hydrophobic icariin is preloaded onto MgO/MgCO3 (11 in weight ratio) particles at different amounts and then the particles are encapsulated into biodegradable poly(lactide-co-glycolide) (PLGA) microspheres (PMI) at a fixed fraction (20 wt%). Continuous releases of Mg2+ ion and icariin from the microspheres are detected, showing dependence on icariin amounts. At an optimized moderate loading amount, the resulting PMI-M microspheres display the strongest activation effect on cell biological behaviors among all the designs. By implanting the PMI-M microspheres into rat calvarial defects for 16 weeks, it is found that they can effectively enhance new bone formation, presenting significantly higher capacity in inducing osteogenesis than PMg (containing MgO/MgCO3 but without icariin) and blank PLGA microspheres. Clearly, the released Mg2+ ions are beneficial to osteogenesis, and the coincorporation of icariin exerts supplemental effects in inducing new bone formation, which suggest a promising strategy to regenerate severe bone injuries by designing a dual-release system. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This meta-analysis aims to compare serum uric acid levels among preeclamptic and healthy pregnant women across the various trimesters and provide a summary of the effect size of this biomarker in predicting adverse pregnancy outcomes. MEDLINE, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception. Observational studies were held eligible if they reported serum uric acid among preeclamptic and healthy pregnant women. Meta-analysis was conducted regarding uric acid concentration, diagnostic accuracy, and association with perinatal outcomes. The credibility of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The analysis included 196 studies, comprising 39 540 women. Preeclampsia was associated with significantly elevated uric acid levels during the 1st (mean difference [MD] 0.21 mg/dL, 95% confidence intervals [CI] 0.06-0.35) trimester, 2nd (MD 1.41 mg/dL, 95% CI 0.78-2.05) trimester, and 3rd (MD 2.26 mg/dL, 95% CI 2.12-2.40) trimester. Higher uric acid was estimated for severe preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelet syndrome. The sensitivity for adverse perinatal outcome prediction ranged from 67.3% to 82.7% and the specificity from 47.7% to 70.7%. In conclusion, it is suggested that serum uric acid levels are increased in preeclampsia and can be used to predict disease severity and pregnancy complications. Future prospective studies should verify these outcomes, assess the optimal cutoffs, and incorporate uric acid to combined predicting models. © 2020 Wiley Periodicals, Inc.Nanoparticles (NPs) are used in food packaging and processing and have become an integral part of many commonly ingested products. There are few studies that have focused on the interaction between ingested NPs, gut function, the mucus layer, and the gut microbiota. In this work, an in vitro model of gastrointestinal (GI) tract is used to determine whether, and how, the mucus layer is affected by the presence of Gram-positive, commensal Lactobacillus rhamnosus; Gram-negative, opportunistic Escherichia coli; and/or exposure to physiologically relevant doses of pristine or digested TiO2 NPs. Caco-2/HT29-MTX-E12 cell monolayers are exposed to physiological concentrations of bacteria (expressing fluorescent proteins) and/or TiO2 nanoparticles for a period of 4 h. To determine mucus thickness and composition, cell monolayers are stained with alcian blue, periodic acid schiff, or an Alexa Fluor 488 conjugate of wheat germ agglutinin. It is found that the presence of both bacteria and nanoparticles alter the thickness and composition of the mucus layer. Changes in the distribution or pattern of mucins can be indicative of pathological conditions, and this model provides a platform for understanding how bacteria and/or NPs may interact with and alter the mucus layer. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.In the design of solar-energy conversion electrochemical systems, it is important to consider that natural sunlight fluctuates. By taking nitrous acid photoreduction as an example, the present work has shown that the reaction pathway, and hence the reaction products, dynamically responded to the variation of light intensity. Under irradiation, the photooxidation of methanol (as sacrificial agent) on TiO 2 and the reduction of HNO 2 on Cu-modified covalent triazine framework (Cu-CTF) were electrically coupled, which led to the photoreduction of HNO 2  without an external bias. The dominant reaction product changes from N 2 O to NH 4 + with an increase in the light intensity. The operating potential also shifted negatively (or positively) when the light intensity was increased (or decreased). These results indicate that a change of the reaction pathway was triggered by a change of the operating potential of the Cu-CTF catalysts under varying light intensity. Such a light-intensity dependent change of the reaction pathway is particularly important in systems that use photoresponsive electrodes and where multiple products can be obtained, such as the solar-driven reduction of carbon dioxide and nitrogen oxides. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Two-dimensional materials created a leap in material science research, especially in the section of energy conversion or/and storage. Borophene and its spherical counterpart boron fullerene represent the emerging type of materials which gained great attention in the whole area of advanced energy materials and technologies. Owing to their prominent features such as electronic environment and geometry, borophene and boron fullerene endowed versatile applications such as supercapacitors, superconductors, anode materials for photochemical water splitting, and biosensors. Herein, one of the most promising applications/areas as hydrogen storage is discussed. Boron fullerenes have been considered and discussed for its hydrogen storage applications, and recently borophene is also included in the list of materials with promising hydrogen storage properties. Studies focus mainly on doped borophene systems over pristine borophene due to enhanced features available on decoration with metal atoms. This review article introduces the very recent progress and novel paradigms on the aspects of both borophene derivatives and boron fullerene-based systems reported for hydrogen storage, focused on the synthesis, physiochemical properties, hydrogen storage mechanism and practical applications. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Great progress has been made in miRNA nanodelivery for the treatment of myocardial infarction (MI). However, miRNA nanodelivery within the infarct is impeded by microvascular obstruction as a local circulatory disorder caused by microthrombus formation in microvessels. Knowing that low molecular weight heparin (LMWH) can effectively prevent microthrombus formation in microcirculation, it is hypothesized whether surface modification of the nanocarrier with LMWH can overcome microvascular obstruction in the infarct area for better miRNA delivery. Herein, a novel nanocomlex consisting of dendrigraft poly-l-lysine (DGL)-loaded miR-1 inhibitor as the core to decrease apoptosis of cardiomyocytes and LMWH as the shell to overcome microvascular obstruction of the infarct area is developed. The results show that this anti-coagulative nanocomlex is able to reduce microthrombus formation in microvessels and inhibit blood-coagulation factor Xa, thereby overcoming microvascular obstruction in the infarct area. Ruxolitinib inhibitor In addition, it further enhances the uptake of miR-1 inhibitor within the infarct and decreases myocardiocyte apoptosis, thus improving the cardiac function and attenuating the myocardial fibrosis. In conclusion, modification of DGL-loaded miR-1 inhibitor with LMWH helps overcome microvascular obstruction in delivering the drug to the infarct area, thus providing a promising therapeutic strategy for achieving a better therapeutic outcome of MI. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Nanotechnology is enjoying an impressive growth and the global nanotechnology industry is expected to exceed US$ 125 billion by 2024. Based on these successes, there are notions that enough is known and efforts on engineered nanomaterial environmental health and safety (nano-EHS) research should be put on the back burner. However, there are recent events showing that it is not the case. The US Food and Drug Administration found ferumoxytol (carbohydrate-coated superparamagnetic iron oxide nanoparticle) for anemia treatment could induce lethal anaphylactic reactions. The European Union will categorize TiO2 as a category 2 carcinogen due to its inhalation hazard and France banned use of TiO2 (E171) in food from January 1, 2020 because of its carcinogenic potential. Although nanoindustry is seemingly in a healthy state, growth could be hindered for the lack of certainty and more nano-EHS research is needed for the sustainable growth of nanoindustry. Herein, the current knowledge gaps and the way forward are elaborated.