Comparative Bioequivalence and Food Effect of Two Formulations of 30-mg Nifedipine Controlled-Release Tablets in Healthy Chinese Adults.

Nifedipine is a potent antihypertensive medication classified as a dihydropyridine calcium channel blocker. The objective of this trial was to assess the bioequivalence of a 30-mg nifedipine controlled-release tablet and a reference drug in a cohort of healthy Chinese individuals. Two independent open-label, randomized, single-dose, crossover studies were conducted, 1 under fasting conditions (N = 44, with 1 participant dropping out midway) and the other under fed conditions (N = 44, with 4 participants dropping out midway). Plasma concentrations of nifedipine were determined using liquid chromatography-mass spectrometry, and pharmacokinetic (PK) parameters were calculated using noncompartmental analysis with Phoenix WinNonlin 8.0 software. In both fasting and fed studies, reasonable bioequivalence was observed for the PK parameters of both the test product and the reference drug. A good safety profile was demonstrated for both the test product and reference drug, with no serious adverse events reported, and both were similarly well tolerated. An important observation with food coadministration was that systemic exposure to nifedipine (based on area under the curve, AUC0-∞) was reduced by approximately 12%. The bioequivalence of the test product and reference drug under fasting/fed conditions in healthy subjects in China was demonstrated by the study results.

ZIFs derived polyhedron with cobalt oxide nanoparticles as novel nanozyme for the biomimetic catalytic oxidation of glucose and non-enzymatic sensor.

The global prevalence of diabetes makes it a significant work to develop flagship sensors in glucose monitoring technology. Particularly, exploring highly active nanocomposites as biomimetic catalysts for the enzymatic reaction of glucose is extremely attractive in non-enzymatic glucose sensing. Herein, nitrogen-doped hollow carbon nano-polyhedron implanted with Co3O4 nanoparticles (NHCN-Co3O4) was introduced as nanozyme for the catalytic oxidation of glucose. NHCN-Co3O4 was synthesized by a two-step redox carbonization of zeolitic imidazolate frameworks. Morphology and structure characterizations revealed that NHCN-Co3O4 was a rhombic nano-dodecahedron with hollow N-doped carbon frameworks. In the frameworks, well-defined Co3O4 nanoparticles were embedded. With highly porous N-doped graphitization structure and embedded Co3O4, NHCN-Co3O4 displayed a distinguished biomimetic catalysis towards the direct oxidation of glucose at a low onset potential of 0.30 V. The biomimetic catalysis of glucose oxidation at NHCN-Co3O4 was so efficient that a steady-state current signal could be established within 3 s. By using NHCN-Co3O4 as nanozyme, a brilliant non-enzymatic glucose sensor was developed with a very low detection limit of 0.2 µM and broad detection range from 1.0 µM to 32.0 mM. Besides, NHCN-Co3O4 sensor also displayed an effective anti-interference capability towards the simulated interfering species including small biomolecules, amino acids, and chloride ion. Furthermore, notable repeatability, reproducibility and long-term stability were also presented. Finally, the successful blood sugar detection in human serum strongly manifests the possible real application of NHCN-Co3O4 sensor.

Nitrogen-doped carbon dodecahedron embedded with cobalt nanoparticles for the direct electro-oxidation of glucose and efficient nonenzymatic glucose sensing.

Developing high-performance sensors for glucose detection is extremely desirable for clinical diagnostics and life sciences. Particularly, it is greatly attractive to exploit composite materials with large surface area, doped heterojunction and non-precious metal as highly active electro-catalysts for nonenzymatic glucose sensing. Herein, we reported a N-doped carbon dodecahedron embedded with Co nanoparticles (Co@NCD) for the direct electro-oxidation of glucose and efficient nonenzymatic glucose detection. Co@NCD was synthesized by the pyrolysis of zeolitic imidazolate framework (ZIF). Field emission scanning electron microscope, high-resolution transmission electron microscope, powder X-ray diffraction, X-ray photoelectron spectroscopy and nitrogen adsorption-desorption experiments were performed to investigate Co@NCD. A well-defined dodecahedron morphology with uniform size and shape was observed. Besides, the original framework was carbonized after pyrolysis leading to a hollow and porous graphite dodecahedron containing N-doped carbon heterojunction. Moreover, Co nanoparticles were evenly distributed into the dodecahedron. With porous structure, N-doped carbon and embedded Co nanoparticles, Co@NCD displayed a notable electro-catalysis towards the direct oxidation of glucose (onset potential: 0.20 V). By using Co@NCD as electro-catalyst, an efficient nonenzymatic glucose sensor was obtained with a rapid amperometric response (within 1 s), low detection limit (0.11 µM) and broad detection range (0.2 µM-12.0 mM). In addition, remarkable selectivity, repeatability, reproducibility and long-term stability were also observed. Finally, Co@NCD prepared sensor was also successfully applied to the detection of glucose in human serum. Our results suggested that ZIF templated method could be an innovative solution for active composite catalysts in biomolecular electro-catalysis and Co@NCD prepared sensor could be a substantial preferable sensing platform for the nonenzymatic glucose detection.

Upregulation of CFTR Protects against Palmitate-Induced Endothelial Dysfunction by Enhancing Autophagic Flux.

Saturated free fatty acids (FFAs) elevate in metabolic symptom leading to endothelial dysfunction. Cystic fibrosis transmembrane regulator (CFTR) functionally expresses in endothelial cells. The role of CFTR in FFA-induced endothelial dysfunction remains unclear. This study is aimed at exploring the effects of CFTR on palmitate- (PA-) induced endothelial dysfunction and its underlying mechanisms. We found that PA-induced endothelial dysfunction is characterized by a decrease of cell viability, reduction of NO generation and mitochondrial membrane potential, impairment of the tube formation, but an increase of ROS generation and cell apoptosis. Simultaneously, PA decreased CFTR protein expression. CFTR agonist Forskolin upregulated CFTR protein expression and protected against PA-induced endothelial dysfunction, while CFTR knockdown exacerbated endothelial dysfunction induced by PA and blunted the protective effects of Forskolin. In addition, PA impaired autophagic flux, and autophagic flux inhibitors aggravated PA-induced endothelial apoptosis. CFTR upregulation significantly restored autophagic flux in PA-insulted endothelial cells, which was involved in increasing the protein expression of Atg16L, Atg12-Atg5 complex, cathepsin B, and cathepsin D. In contrast, CFTR knockdown significantly inhibited the effects of Forskolin on autophagic flux and the expression of the autophagy-regulated proteins. Our findings illustrate that CFTR upregulation protects against PA-induced endothelial dysfunction by improving autophagic flux and underlying mechanisms are involved in enhancing autophagic signaling mediated by the Atg16L-Atg12-Atg5 complex, cathepsin B, and cathepsin D. CFTR might serve as a novel drug target for endothelial protection in cardiovascular diseases with a characteristic of elevation of FFAs.