Utility of Integrated Analysis of Pharmacogenomics and Pharmacometabolomics in Early Phase Clinical Trial: A Case Study of a New Molecular Entity

In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials

Exploring the influence of the level of technology and expected functions in product semantic

This study attempted to explore how pragmatic and hedonic values are influenced by the level of technology and what particular functions have to be considered in the context of smart technologydriven design in terms of Pragmatic Value (PV) and Hedonic Value (HV). An on-line questionnaire survey was developed to answer the research questions. A total of 104 respondents participated in the survey. As target product for the study, analog watch and smart watch were selected as representative of low and high technology respectively. Semantic Differentials on PV and HV were used and expected functions were investigated via an open question. The results indicate that there are some differences between analog and smart watches in terms of PV and HV. Regarding expected functions, significant differences were identified in the study. The findings from the study could provide a better understanding of the relationship between PV and HV in terms of level of technology. If it is considered in product development process, it may contribute to an increase of user satisfaction with smarttechnology based product and service

A Practical Hydrazine-Carbothioamide-Based Fluorescent Probe for the Detection of Zn²⁺: Applications to Paper Strip, Zebrafish and Water Samples

A practical hydrazine-carbothioamide-based fluorescent chemosensor TCC (N-(4-chlorophenyl)-2-(thiophene-2-carbonyl)hydrazine-1-carbothioamide) was applied for Zn2+ detection. TCC exhibited selective fluorescence emission for Zn2+ and did not show any interference with other metal ions. In particular, TCC was utilized for the detection of Zn2+ in paper strips, zebrafish and real water samples. TCC could detect Zn2+ down to 0.39 μM in the solution phase and 51.13 μM in zebrafish. The association ratio between TCC and Zn2+ was determined to be 2:1 by ESI-mass and Job plot. The sensing mechanism of TCC for Zn2+ was illustrated to be a chelation-enhanced fluorescence process through spectroscopic experiments and theoretical calculations

A Practical Hydrazine-Carbothioamide-Based Fluorescent Probe for the Detection of Zn2+: Applications to Paper Strip, Zebrafish and Water Samples

A practical hydrazine-carbothioamide-based fluorescent chemosensor TCC (N-(4-chlorophenyl)-2-(thiophene-2-carbonyl)hydrazine-1-carbothioamide) was applied for Zn2+ detection. TCC exhibited selective fluorescence emission for Zn2+ and did not show any interference with other metal ions. In particular, TCC was utilized for the detection of Zn2+ in paper strips, zebrafish and real water samples. TCC could detect Zn2+ down to 0.39 &mu;M in the solution phase and 51.13 &mu;M in zebrafish. The association ratio between TCC and Zn2+ was determined to be 2:1 by ESI-mass and Job plot. The sensing mechanism of TCC for Zn2+ was illustrated to be a chelation-enhanced fluorescence process through spectroscopic experiments and theoretical calculations

Culture-dependent and -independent investigations of bacterial migration into doenjang from its components meju and solar salt.

We determined bacterial migration into doenjang from its components, meju and solar salt using culture-based and 16S rRNA gene-based culture-independent techniques (pyrosequencing of total DNA). Pyrosequencing results suggested that the bacterial communities of meju, but not solar salt, significantly affected those of doenjang communities. Culture-based pyrosequencing analysis yielded similar results. These results indicate that most predominant bacterial species in doenjang migrated from meju, not solar salt. We therefore believe that the present study is one of the most comprehensive comparisons of bacterial communities of fermented soybeans using culture-dependent and -independent methods. Furthermore, pyrosequencing of the V3 and V4 regions of bacterial 16S rRNA did not distinguish among Bacillus amyloliquefaciens, B. siamensis, and B. velezensis as well as between Enterococcus faecium and E. hirae

Enhancement of Light Absorption in Photovoltaic Devices using Textured Polydimethylsiloxane Stickers

We designed and fabricated a random-size inverted-pyramid-structured polydimethylsiloxane (RSIPS-PDMS) sticker to enhance the light absorption of solar cells and thus increase their efficiency. The fabricated sticker was laminated onto bare-glass and crystalline-silicon (c-Si) surfaces; consequently, low solar-weighted reflectance values were obtained for these surfaces (6.88% and 17.2%, respectively). In addition, we found that incident light was refracted at the PDMS-air interface of each RSIPS, which redirected the incident power and significantly increased the optical path length in the RSIPS-PDMS sticker which was 14.7% greater than that in a flat-PDMS sticker. Moreover, we investigated power reflection and propagation through the RSIPS-PDMS sticker using a finite-difference time-domain method. By attaching an RSIPS-PDMS sticker onto both an organic solar cell (OSC) based on a glass substrate and a c-Si solar cell, the power conversion efficiency of the OSC and the c-Si solar cell were increased from 8.57% to 8.94% and from 16.2% to 17.9%, respectively. Thus, the RSIPS-PDMS sticker is expected to be universally applicable to the surfaces of solar cells to enhance their light absorption

Olfactory Stimulation by Fennel (Foeniculum vulgare Mill.) Essential Oil Improves Lipid Metabolism and Metabolic Disorders in High Fat-Induced Obese Rats

In this study, odor components were analyzed using gas chromatography/mass spectrometry (GC/MS) and solid-phase microextraction (SPME), and odor-active compounds (OACs) were identified using GC-olfactometry (GC-O). Among the volatile compounds identified through GC-O, p-anisaldehyde, limonene, estragole, anethole, and trans-anethole elicit the fennel odor. In particular, trans-anethole showed the highest odor intensity and content. Changes in body weight during the experimental period showed decreasing values of fennel essential oil (FEO)-inhaled groups, with both body fat and visceral fat showing decreased levels. An improvement in the body&rsquo;s lipid metabolism was observed, as indicated by the increased levels of cholesterol and triglycerides and decreased levels of insulin in the FEO-inhaled groups compared to group H. Furthermore, the reduction in systolic blood pressure and pulse through the inhalation of FEO was confirmed. Our results indicated that FEO inhalation affected certain lipid metabolisms and cardiovascular health, which are obesity-related dysfunction indicators. Accordingly, this study can provide basic research data for further research as to protective applications of FEO, as well as their volatile profiles

Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity

Firmicutes and Bacteroidetes, 2 major phyla of gut microbiota, are involved in lipid and bile acid metabolism to maintain systemic energy homeostasis in host. Recently, accumulating evidence has suggested that dietary changes promptly induce the alteration of abundance of both Firmicutes and Bacteroidetes in obesity and its related metabolic diseases. Nevertheless, the metabolic roles of Firmicutes and Bacteroidetes on such disease states remain unclear. The aim of this study was to determine the effects of antibiotic-induced depletion of Firmicutes and Bacteroidetes on dysregulation of energy homeostasis in obesity. Treatment of C57BL/6J mice with the antibiotics (vancomycin [V] and bacitracin [B]), in the drinking water, before diet-induced obesity (DIO) greatly decreased both Firmicutes and Bacteroidetes in the gut as revealed by pyrosequencing of the microbial 16S rRNA gene. Concomitantly, systemic glucose intolerance, hyperinsulinemia, and insulin resistance in DIO were ameliorated via augmentation of GLP-1 secretion (active form; 2.03-fold, total form; 5.09-fold) independently of obesity as compared with untreated DIO controls. Furthermore, there were increases in metabolically beneficial metabolites derived from the gut. Together, our data suggest that Firmicutes and Bacteroidetes potentially mediate insulin resistance through modulation of GLP-1 secretion in obesity.—Hwang, I., Park, Y. J., Kim, Y. -R., Kim, Y.N.,Ka, S., Lee,H.Y., Seong, J.K., Seok,Y. -J., andKim, J.B. Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity.OAIID:oai:osos.snu.ac.kr:snu2015-01/102/0000005231/3ADJUST_YN:YEMP_ID:A072580DEPT_CD:3344CITE_RATE:5.043FILENAME:cv no.111.pdfDEPT_NM:생명과학부SCOPUS_YN:YCONFIRM:

Olfactory Stimulation with Volatile Aroma Compounds of Basil (<i>Ocimum basilicum</i> L.) Essential Oil and Linalool Ameliorates White Fat Accumulation and Dyslipidemia in Chronically Stressed Rats

We explored the physiological effects of inhaling basil essential oil (BEO) and/or linalool and identified odor-active aroma compounds in BEO using gas chromatography/mass spectrometry (GC–MS) and GC–olfactometry (GC–O). Linalool was identified as the major volatile compound in BEO. Three groups of rats were administered BEO and linalool via inhalation, while rats in the control group were not. Inhalation of BEO for 20 min only reduced the total weight gain (190.67 ± 2.52 g) and increased the forced swimming time (47.33 ± 14.84 s) compared with the control group (219.67 ± 2.08 g, 8.33 ± 5.13 s). Inhalation of BEO for 5 min (392 ± 21 beats/min) only reduced the pulse compared with the control group (420 ± 19 beats/min). Inhalation of linalool only reduced the weight of white adipose tissue (5.75 ± 0.61 g). The levels of stress-related hormones were not significantly different among the groups. The total cholesterol and triglyceride levels decreased after inhalation of BEO for 20 min (by more than −10% and −15%, respectively). Low-density lipoprotein cholesterol levels were lowered (by more than −10%) by the inhalation of BEO and linalool, regardless of the inhalation time. In particular, BEO inhalation for 20 min was associated with the lowest level of low-density lipoprotein cholesterol (53.94 ± 2.72 mg/dL). High-density lipoprotein cholesterol levels increased after inhalation of BEO (by more than +15%). The atherogenic index and cardiac risk factors were suppressed by BEO inhalation. Animals exposed to BEO and linalool had no significant differences in hepatotoxicity. These data suggest that the inhalation of BEO and linalool may ameliorate cardiovascular and lipid dysfunctions. These effects should be explored further for clinical applications