scholarly journals Urinary Metabolomic Profiling after Administration of Corydalis Tuber and Pharbitis Seed Extract in Healthy Korean Volunteers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 522
Author(s):  
Hyeon-Cheol Jeong ◽  
Jung Eun Park ◽  
Yohan Seo ◽  
Min-Gul Kim ◽  
Kwang-Hee Shin

Pharmacometabolomics is a useful tool to identify biomarkers that can assess and predict response after drug administration. The primary purpose of pharmacometabolomics is to better understand the mechanisms and pathways of a drug by searching endogenous metabolites that have significantly changed after drug administration. DA-9701, a prokinetic agent, consists of Pharbitis seed and Corydalis tube extract and it is known to improve the gastrointestinal motility. Although the overall mechanism of action of DA-9701 remains unclear, its active ingredients, corydaline and chlorogenic acid, act as a 5-HT3 and D2 receptor antagonist and 5-HT4 receptor agonist. To determine the significant metabolites after the administration of DA-9701, a qualitative analysis was carried out using ultra-high performance liquid chromatography coupled with orbitrap mass spectrometer followed by a multivariate analysis. Seven candidates were selected and a statistical analysis of fold change was performed over time. Our study concluded that all the seven selected metabolites were commonly involved in lipid metabolism and purine metabolism.

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2194
Author(s):  
Kamil Łuczykowski ◽  
Natalia Warmuzińska ◽  
Sylwia Operacz ◽  
Iga Stryjak ◽  
Joanna Bogusiewicz ◽  
...  

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.


2019 ◽  
Vol 26 (3) ◽  
pp. 363-386
Author(s):  
Seung Ho Park ◽  
Gerardo R. Ungson

Purpose The purpose of this paper is to uncover the underlying drivers of sustained high performing companies based on a field study of 127 companies in Brazilian, Russian, Indian and Chinese (BRIC) and Association of Southeast Asian Nations (ASEAN) emerging markets. Understanding these companies provides a complementary way of appraising the growth, development and transformation of emerging markets. The authors synthesize the findings in an overarching framework that covers six strategies for building and sustaining legacy that leads to the succession of intergenerational wealth over time: overcoming institutional voids, inclusive markets, deepening localization, nurturing government support, building core competencies and harnessing human capital. The authors relate these strategies to different levels of development using Prahalad and Hart’s BOP framework. Design/methodology/approach This study examines the underlying drivers of sustained high-performance companies based on field studies from an initial set of 105,260 BRIC companies and close to 500 companies in ASEAN. The methods employed four screening tests to arrive at a selection of the highest-performing firms: 70 firms in the BRIC nations and 58 firms from ASEAN. Following the selection, the authors constructed cases using primary interviews and secondary data, with the assistance of Ernst & Young and with academic colleagues in Manila. These studies were originally conducted in two separate time periods and reported accordingly. This paper synthesizes the findings of these two studies to arrive at an extended integrative framework. Findings From the cases, the authors examine six strategies for building and sustaining legacy that lead to high performance over time: overcoming institutional voids, creating inclusive markets, deepening localization, nurturing government support, building core competencies and harnessing human capital. To address the evolving state of institutional voids in these countries, the authors employ similar methods to hypothesize the placement of these strategies in the context of the world economic pyramid, initially formulated as the “bottom of the pyramid” framework. Originality/value This paper synthesizes and extends the authors’ previous works by proposing the concept of legacy to describe the emergence and succession of local exemplary firms in emerging markets. This study aims to complement extant measures of nation-growth based primarily on GDP. The paper also extends the literature on institutional voids in shifting the focus from the mix of voids to their evolving state. Altogether, the paper provides a complementary narrative on assessing the market potential of emerging markets by adopting several categories of performance.


2020 ◽  
Vol 70 (1) ◽  
pp. 181-189
Author(s):  
Guy Baele ◽  
Mandev S Gill ◽  
Paul Bastide ◽  
Philippe Lemey ◽  
Marc A Suchard

Abstract Markov models of character substitution on phylogenies form the foundation of phylogenetic inference frameworks. Early models made the simplifying assumption that the substitution process is homogeneous over time and across sites in the molecular sequence alignment. While standard practice adopts extensions that accommodate heterogeneity of substitution rates across sites, heterogeneity in the process over time in a site-specific manner remains frequently overlooked. This is problematic, as evolutionary processes that act at the molecular level are highly variable, subjecting different sites to different selective constraints over time, impacting their substitution behavior. We propose incorporating time variability through Markov-modulated models (MMMs), which extend covarion-like models and allow the substitution process (including relative character exchange rates as well as the overall substitution rate) at individual sites to vary across lineages. We implement a general MMM framework in BEAST, a popular Bayesian phylogenetic inference software package, allowing researchers to compose a wide range of MMMs through flexible XML specification. Using examples from bacterial, viral, and plastid genome evolution, we show that MMMs impact phylogenetic tree estimation and can substantially improve model fit compared to standard substitution models. Through simulations, we show that marginal likelihood estimation accurately identifies the generative model and does not systematically prefer the more parameter-rich MMMs. To mitigate the increased computational demands associated with MMMs, our implementation exploits recent developments in BEAGLE, a high-performance computational library for phylogenetic inference. [Bayesian inference; BEAGLE; BEAST; covarion, heterotachy; Markov-modulated models; phylogenetics.]


2015 ◽  
Vol 20 (4) ◽  
pp. 424-442 ◽  
Author(s):  
Mariella Miraglia ◽  
Guido Alessandri ◽  
Laura Borgogni

Purpose – Previous literature has recognized the variability of job performance, calling attention to the inter-individual differences in performance change. Building on Murphy’s (1989) theoretical model of performance, the purpose of this paper is to verify the existence of two distinct classes of performance, reflecting stable and increasing trends, and to investigate which personal conditions prompt the inclusion of individuals in one class rather than the other. Design/methodology/approach – Overall job performance was obtained from supervisory ratings for four consecutive years for 410 professionals of a large Italian company going through significant reorganization. Objective data were merged with employees’ organizational tenure and self-efficacy. Growth Mixture Modeling was used. Findings – Two main groups were identified: the first one started at higher levels of performance and showed a stable trajectory over time (stable class); the second group started at lower levels and reported an increasing trajectory (increasing class). Employees’ with stronger efficacy beliefs and lower tenure were more likely to belong to the stable class. Originality/value – Through a powerful longitudinal database, the nature, the structure and the inter-individual differences in job performance over time are clarified. The study extends Murphy’s (1989) model, showing how transition stages in job performance may occur also as a result of organizational transformation. Moreover, it demonstrates the essential role of self-efficacy in maintaining high performance levels over time.


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