Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes

Cytochrome p450 (CYP450) enzymes are predominantly involved in Phase I metabolism of xenobiotics. In this study, the CYP450 isoforms involved in xanthotoxol metabolism were identified using recombinant CYP450s. In addition, the inhibitory effects of xanthotoxol on eight CYP450 isoforms and its pharmacokinetic parameters were determined using human liver microsomes. CYP1A2, one of CYP450s, played a key role in the metabolism of xanthotoxol compared to other CYP450s. Xanthotoxol showed stronger inhibition on CYP3A4 and CYP1A2 compared to other isoenzymes with the IC50 of 7.43 μM for CYP3A4 and 27.82 μM for CYP1A2. The values of inhibition kinetic parameters (Ki) were 21.15 μM and 2.22 μM for CYP1A2 and CYP3A4, respectively. The metabolism of xanthotoxol obeyed the typical monophasic Michaelis-Menten kinetics and Vmax, Km, and CLint values were calculated as 0.55 nmol·min−1·mg−1, 8.46 μM, and 0.06 mL·min−1·mg−1. In addition, the results of molecular docking showed that xanthotoxol was bound to CYP1A2 with hydrophobic and π-π bond and CYP3A4 with hydrogen and hydrophobic bond. We predicted the hepatic clearance (CLh) and the CLh value was 15.91 mL·min−1·kg−1 body weight. These data were significant for the application of xanthotoxol and xanthotoxol-containing herbs

Menthyl 2-oxo-2H-chromene-3-carboxyl­ate

The title compound, C20H24O4, was synthesized from the reaction of 2-oxo-2H-chromene-3-acyl chloride and menthol. The mean plane of the ester group and that of the four essentially planar (maximum deviation 0.0112 Å) C atoms of the chair-form cyclo­hexyl ring form dihedral angles of 43.8 (3) ° and 81.8 (1)°, respectively, with the mean plane of the coumarin ring system. In the crystal structure, weak inter­molecular C—H⋯O hydrogen bonds connect the mol­ecules into a two-dimensional network

2-Cyano-N,N-dimethyl­acetamide

In the crystal structure of the title compound, C5H8N2O, mol­ecules are linked by weak C—H⋯O hydrogen bonds, forming a three-dimensional network

A bioinspired bubble removal method in microchannels based on angiosperm xylem embolism repair

It is difficult to remove and eliminate bubbles in microchannels in many devices used in various biomedical fields, such as those needed for microfluidic immunoassays, point-of-care testing, and cell biology evaluations. Accumulated bubbles are associated with a number of negative outcomes, including a decrease in device sensitivity, inaccuracy of analysis results, and even functional failure. Xylem conduits of angiosperm have the ability to remove bubbles in obstructed conduits. Inspired by such an embolism repair mechanism, this paper proposes a bioinspired bubble removal method, which exhibits a prominent ability to dissolve bubbles continuously within a large range of flow rates (2 µL/min–850 µL/min) while retaining the stability and continuity of the flow without auxiliary equipment. Such a method also shows significant bubble removal stability in dealing with Newtonian liquids and non-Newtonian fluids, especially with high viscosity (6.76 Pa s) and low velocity (152 nL/min). Such advantages associated with the proposed bioinspired method reveal promising application prospects in macro/microfluidic fields ranging from 3D printing, implantable devices, virus detection, and biomedical fluid processing to microscale reactor operation and beyond

Intramolecular π Stacking in Cationic Iridium(III) Complexes with Phenyl-Functionalized Cyclometalated Ligands: Synthesis, Structure, Photophysical Properties, and Theoretical Studies

The syntheses of two new heteroleptic cationic iridium complexes containing 2,6-diphenylpyridine (Hdppy) and 2,4,6-triphenylpyridine (Htppy) as the cyclometalated ligands, namely, [Ir(dppy)2phen]PF6 (1, phen = 1,10-phenanthroline) and [Ir(tppy)2phen]PF6 (2), are described. The X-ray crystal structure of 2 reveals a distorted octahedral geometry around the Ir center and close intramolecular face-to-face π–π stacking interactions between the pendant phenyl rings at the 2-position of the cyclometalated ligands and the NN ancillary ligand. This represents a new π–π stacking mode in charged Ir complexes. Complexes 1 and 2 are green photoemitters: their photophysical and electrochemical properties are interpreted with the assistance of density functional theory (DFT) calculations. These calculations also establish that the observed intramolecular interactions cannot effectively prevent the lengthening of the Ir–N bonds of the complexes in their metal-centered (3MC) states. Complexes 1 and 2 do not emit light in light-emitting electrochemical cells (LECs) under conditions in which the model compound [Ir(ppy)2phen]PF6 (3) emits strongly. This is explained by degradation reactions of the 3MC state of 1 and 2 under the applied bias during LEC operation facilitated by the enhanced distortions in the geometry of the complexes. These observations have important implications for the future design of complexes for LEC applications

Dye-enhanced graphene oxide for photothermal therapy and photoacoustic imaging

National Basic Research Program of China [2010CB732403]; National Natural Science Foundation of China [21125524, 20975023]; Program for New Century Excellent Talents in the University of China [09-0014]; Program for Changjiang Scholars and Innovative Research Team in University [IRT1116]; National Science Foundation of Fujian Province [2010J06003]Graphene oxide (GO) has many exciting advantages such as easy preparation, low toxicity, good solubility and stability in aqueous solution. However, GO itself has a low near-infrared (NIR) absorption, and thus is not suitable for photothermal therapy and photoacoustic imaging. To overcome this limitation, a novel dye-enhanced GO is prepared utilizing the pi-pi stacking interactions between GO and indocyanine green (ICG). The ICG-GO complex has a high optical absorbance in the NIR region and exhibits excellent photothermal properties under NIR irradiation. In order to improve the cancer-targeting activity, GO was modified with folic acid (FA). In vitro experiments showed that the ICG-GO-FA nanocomposite could be used for targeted photothermal cancer cell destruction. Moreover, the application of the ICG-GO-FA nanocomposite for photoacoustic imaging was also demonstrated

Forschungsdatenzentrum PIAAC: Jahresbericht 2015; Berichtszeitraum 01.01.2015-31.12.2015

We used human gastric epithelial cells (GES-1) line in an ethanol-induced cell damage model to study the protective effect of Veronicastrum axillare and its modulation to NF-κB signal pathway. The goal was to probe the molecular mechanism of V. axillare decoction in the prevention of gastric ulcer and therefore provide guidance in the clinical application of V. axillare on treating injuries from chronic nephritis, pleural effusion, gastric ulcer, and other ailments. The effects of V. axillare-loaded serums on cell viability were detected by MTT assays. Enzyme-linked immunosorbent assay (ELISA) and Real-Time PCR methods were used to analyze the protein and mRNA expression of TNF-α, NF-κB, IκBα, and IKKβ. The results showed that V. axillare-loaded serum partially reversed the damaging effects of ethanol and NF-κB activator (phorbol-12-myristate-13-acetate: PMA) and increased cell viability. The protein and mRNA expressions of TNF-α, NF-κB, IκBα, and IKKβ were significantly upregulated by ethanol and PMA while they were downregulated by V. axillare-loaded serum. In summary, V. axillare-loaded serum has significantly protective effect on GES-1 against ethanol-induced injury. The protective effect was likely linked to downregulation of TNF-α based NF-κB signal pathway

Genome-wide characterization of SOS1 gene family in potato (Solanum tuberosum) and expression analyses under salt and hormone stress

Salt Overly Sensitive 1 (SOS1) is one of the members of the Salt Overly Sensitive (SOS) signaling pathway and plays critical salt tolerance determinant in plants, while the characterization of the SOS1 family in potato (Solanum tuberosum) is lacking. In this study, 37 StSOS1s were identified and found to be unevenly distributed across 10 chromosomes, with most of them located on the plasma membrane. Promoter analysis revealed that the majority of these StSOS1 genes contain abundant cis-elements involved in various abiotic stress responses. Tissue specific expression showed that 21 of the 37 StSOS1s were widely expressed in various tissues or organs of the potato. Molecular interaction network analysis suggests that 25 StSOS1s may interact with other proteins involved in potassium ion transmembrane transport, response to salt stress, and cellular processes. In addition, collinearity analysis showed that 17, 8, 1 and 5 of orthologous StSOS1 genes were paired with those in tomato, pepper, tobacco, and Arabidopsis, respectively. Furthermore, RT-qPCR results revealed that the expression of StSOS1s were significant modulated by various abiotic stresses, in particular salt and abscisic acid stress. Furthermore, subcellular localization in Nicotiana benthamiana suggested that StSOS1-13 was located on the plasma membrane. These results extend the comprehensive overview of the StSOS1 gene family and set the stage for further analysis of the function of genes in SOS and hormone signaling pathways

Malignant Peritoneum Mesothelioma with Hepatic Involvement: A Single Institution Experience in 5 Patients and Review of the Literature

Malignant peritoneal mesothelioma with invasion of the liver is an invariably fatal disease. We aimed to clarify the characteristics of malignant peritoneal mesothelioma cases with liver involvement. The clinical presentation, computed tomography images, and immunohistochemical and histopathological features of 5 patients with malignant peritoneal mesothelioma and liver involvement were evaluated. The diagnosis was established by imaging and immune profiles of the tumours. A review of 8 cases with primary or invading malignant mesothelioma in liver is presented. All 5 mesothelioma cases were asbestos-related. CT images of malignant peritoneal mesothelioma with the liver involvement typically showed that the lesion grew inside the liver along the capsule and was possibly accompanied by capsule breakthrough and extrahepatic infiltration. The tumours exhibited a common epithelioid appearance in all 5 patients and most cases revealed positive Cal, CK, and MC with negative CEA and HeP. Different from our findings, the review of literature revealed that most malignant mesothelioma of liver was due to primary intrahepatic malignant mesothelioma. Finally, we concluded that the diagnosis of malignant peritoneal mesothelioma cases with liver invasion is reliably achieved by the history of asbestos exposure, the characteristic CT imaging, and immune profiles of the tumours