Identification of the Metabolic Enzyme Involved Morusin Metabolism and Characterization of Its Metabolites by Ultraperformance Liquid Chromatogaphy Quadrupole Time-of-Flight Mass Spectrometry (UPLC/Q-TOF-MS/MS)

Morusin, the important active component of a traditional Chinese medicine, Morus alba L., has been shown to exhibit many vital pharmacological activities. In this study, six recombinant CYP450 supersomes and liver microsomes were used to perform metabolic studies. Chemical inhibition studies and screening assays with recombinant human cytochrome P450s were also used to characterize the CYP450 isoforms involved in morusin metabolism. The morusin metabolites identified varied greatly among different species. Eight metabolites of morusin were detected in the liver microsomes from pigs (PLMs), rats (RLMs), and monkeys (MLMs) by LC-MS/MS and six metabolites were detected in the liver microsomes from humans (HLMs), rabbits (RAMs), and dogs (DLMs). Four metabolites (M1, M2, M5, and M7) were found in all species and hydroxylation was the major metabolic transformation. CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, and CYP2C19 contributed differently to the metabolism of morusin. Compared to other CYP450 isoforms, CYP3A4 played the most significant role in the metabolism of morusin in human liver microsomes. These results are significant to better understand the metabolic behaviors of morusin among various species

Association between plasma fluorescent oxidation products and erectile dysfunction: A prospective study

Background: Existing epidemiological studies of the association between oxidative stress and erectile dysfunction (ED) are sparse and inconclusive, which is likely due to cross-sectional design and small sample size. Therefore, we investigated the association between biomarkers of oxidative stress and ED in prospective setting among a relatively large sample size of men. Methods: We conducted the prospective study among 917 men ages between 47 and 80 years at the time of blood draw, which is a part of nested prospective case–control study of prostate cancer in the Health Professionals Follow-up Study. Plasma fluorescent oxidation products (FlOPs), a global biomarker for oxidative stress, were measured at three excitation/emission wavelengths (360/420 nm named as FlOP_360; 320/420 nm named as FlOP_320 and 400/475 nm named as FlOP_400). Results: Approximately 35 % of men developed ED during follow-up. We did not find an independent association between FlOP_360, FlOP_320, FlOP_400 and risk of ED in the multivariable adjusted model (Tertile 3 vs. tertile 1: odds ratio [OR] = 0.90, 95 % confidence interval [CI] = 0.61-1.34, Ptrend = 0.54 for FlOP_360; OR = 0.73, 95 % CI = 0.49-1.07, Ptrend = 0.27 for FlOP_320; and OR = 0.98, 95 % CI = 0.66-1.45, Ptrend = 0.72 for FlOP_400). Further analysis of the association between FlOPs and ED in the fasting samples or controls only (free of prostate cancer incidence) did not change the results appreciably. Conclusions: Plasma FlOPs were not associated with the risk of ED, suggesting oxidative stress may not be an independent risk factor for ED. Electronic supplementary material The online version of this article (doi:10.1186/s12894-015-0083-9) contains supplementary material, which is available to authorized users

Eternal Flames: Living Memories of the Pacific War

Funds requested for an innovative website that provides a living archive of Pacific War memories in multiple languages. Our prototype provides a social media and multi-lingual database structure enabling communication between researchers, war survivors, and the general public in English, Japanese, Chinese, and Korean. This site facilitates research on the circulation of war memories throughout the Pacific region and across linguistic boundaries. Online participants will transcribe, translate, tag, and add context to user-contributed archive posts. The architecture makes transparent the negotiations and contested categories of memory-in-translation. In this online environment, users can confront the cultural embeddedness of language, and researchers can trace the transformations of memory as it travels across cultural boundaries. As an open source tool, our online platform can be applied in various contexts to address the language barrier issue that is so central to the humanities

Global biomarkers of oxidative stress and fractures: a matched case-control study

BackgroundEvidence for a relationship between oxidative stress and osteoporotic fractures in humans is limited. Fluorescent oxidation products (FlOPs, excitation/emission wavelengths 320/420nm denoted FlOP_320; 360/420nm [FlOP_360]; and 400/475nm [FlOP_400]) are global biomarkers of oxidative stress, and reflect oxidative damage to proteins, phospholipids, and nucleic acids. We investigated the association between FlOPs and a recent osteoporotic fracture.MethodsWe conducted a case-control study in a Chinese population aged 50 years or older. A recent osteoporotic fracture in the cases was confirmed by x-ray. Cases were matched with community-based non-fracture controls (1:2 ratio) for age (± 4 years) and sex. In addition, we conducted a sensitivity unmatched case-control study which included all fracture cases and all eligible non-fracture controls prior to matching. Plasma FlOPs were measured with a fluorescent microplate reader. We used unconditional logistic regression to analyze the association between FlOPs (per 1-SD increase in logarithmic scale) and fracture; odds ratios (OR) and 95% confidence intervals (95% CI) were reported.ResultsForty-four cases and 88 matched controls (mean age: 68.2 years) were included. After covariate adjustment (i.e., body mass index, physical activity, and smoking), higher FlOP_360 (OR = 1.85; 95% CI = 1.03 – 3.34) and FlOP_400 (OR = 13.29; 95% CI = 3.48 – 50.69) levels, but not FlOP_320 (OR = 0.56; 95% CI = 0.27 – 1.15), were associated with increased fracture risk. Subgroup analyses by fracture site and unmatched case-control study found comparable associations of FlOP_360 and FlOP_400 with hip and non-hip fractures.ConclusionsHigher FlOP_360 and FlOP_400 levels were associated with increased risk of fracture, and this association was comparable for hip and non-hip fractures. Prospective studies are warranted to confirm this finding

Comparison of the Inhibitory Potential of Bavachalcone and Corylin against UDP-Glucuronosyltransferases

Bavachalcone and corylin are two major bioactive compounds isolated from Psoralea corylifolia L., which has been widely used as traditional Chinese medicine for many years. As two antibiotic or anticancer drugs, bavachalcone and corylin are used in combination with other drugs; thus it is necessary to evaluate potential pharmacokinetic herb-drug interactions (HDI) of the two bioactive compounds. The aim of the present study was to compare the effects of liver UDP-glucuronosyltransferase (UGT) 1A1, UGT1A3, UGT1A7, UGT1A8, UGT 1A10, and UGT2B4 inhibited by bavachalcone and corylin. 4-Methylumbelliferone (4-MU) was used as a nonspecific “probe” substrate. Bavachalcone had stronger inhibition on UGT1A1 and UGT1A7 than corylin which did not inhibit UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A10, and UGT2B4. Data fitting using Dixon and Lineweaver-Burk plots demonstrated the noncompetitive inhibition of bavachalcone against UGT1A1 and UGT1A7-mediated 4-MU glucuronidation reaction. The values of inhibition kinetic parameters (Ki) were 5.41 μM and 4.51 μM for UGT1A1 and UGT1A7, respectively. The results of present study suggested that there was a possibility of UGT1A1 and UGT1A7 inhibition-based herb-drug interaction associated with bavachalcone and provided the basis for further in vivo studies to investigate the HDI potential between bavachalcone and UGT substrates

Human Thrombin Detection Through a Sandwich Aptamer Microarray: Interaction Analysis in Solution and in Solid Phase

We have developed an aptamer-based microarray for human thrombin detection exploiting two non-overlapping DNA thrombin aptamers recognizing different exosites of the target protein. The 15-mer aptamer (TBA1) binds the fibrinogen-binding site, whereas the 29-mer aptamer (TBA2) binds the heparin binding domain. Extensive analysis on the complex formation between human thrombin and modified aptamers was performed by Electrophoresis Mobility Shift Assay (EMSA), in order to verify in solution whether the chemical modifications introduced would affect aptamers/protein recognition. The validated system was then applied to the aptamer microarray, using the solid phase system devised by the solution studies. Finally, the best procedure for Sandwich Aptamer Microarray (SAM) and the specificity of the sandwich formation for the developed aptasensor for human thrombin were optimized

Design and preparation of a novel colon-targeted tablet of hydrocortisone

The objective of this research was to design a new colon-targeted drug delivery system based on chitosan. The properties of the films were studied to obtain useful information about the possible applications of composite films. The composite films were used in a bilayer system to investigate their feasibility as coating materials. Tensile strength, swelling degree, solubility, biodegradation degree, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscope (SEM) investigations showed that the composite film was formed when chitosan and gelatin were reacted jointly. The results showed that a 6:4 blend ratio was the optimal chitosan/gelatin blend ratio. In vitro drug release results indicated that the Eudragit- and chitosan/gelatin-bilayer coating system prevented drug release in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). However, the drug release from a bilayer-coated tablet in SCF increased over time, and the drug was almost completely released after 24h. Overall, colon-targeted drug delivery was achieved by using a chitosan/gelatin complex film and a multilayer coating system

Chemistry of new particle formation and growth events during wintertime in suburban area of Beijing : Insights from highly polluted atmosphere

The high frequency of new particle formation (NPF) events observed under polluted atmospheric conditions is still poorly understood. To improve our understanding of NPF and its effects, the particle number size distribution (3-1000 nm) and submicron particle chemical composition were measured from 4 November 2017 to 17 January 2018 in suburban Beijing. During this intense campaign, 22 NPF events were identified with a frequency of 29%, including 11 cases that occurred under "clean" conditions (C-NPF) and 11 cases that occurred under "polluted" conditions (P-NPF). The observed formation rate (J(3)) and condensation sink were 4.6-148.9 cm(-3).s(-1) and 0.01-0.07 s(-1), and the majority of NPF events occurred when the condensation sink (CS) values below 0.03 s(-1), indicating that condensation vapor likely constitutes the critical limiting factor for NPF events. The correlations between log J(3) and [H2SO4] that close to previous CLOUD experimental results in the majority of NPF events (68%) suggest the high nucleation rates (up to 100 cm(-3).s(-1)) would be attributed by the amines that enhancing sulfuric acid nucleation, while the reminding cases (32%) possibly attributed to the H2SO4-NH3 clustering mechanism, which is supported by the theoretical expectations for H2SO4 nucleation with NH3 simulated by the MALTE_BOX model. The observed growth rate varied from 4.9 to 37.0 mm.h(-1), with the dominant contribution (>60%) from sulfuric acid during the early phases of growth (similar to 4 nm), which was also sufficient to explain the observed Q(GR) for 50 nm)Peer reviewe