Cheminformatic Approach for Deconvolution of Active Compounds in a Complex Mixture - phytoserms in Licorice

ABSTRACT After the validation of our in silico models by using the previous knowledge in this area the alerting phytochemicals from two Glycyrrhiza species (G. glabra and G. uralensis) were clustered. Exhaustive computational mining of licorice metabolome against selected endocrinal and metabolic targets led to the discovery of a unique class of compounds which belong to the dihydrostilbenoids (DHS) class appended with prenyl groups at various positions. To the best of our knowledge this interesting group of compounds has not been studied for their estrogenic activities or PXR activation. In addition some of the bis-prenylated DHS have been reported to be present only in G. uralensis. Another aspect of the current project was to predict the phase I primary metabolites of compounds found in both species of Glycyrrhiza and assess them with computational tools to predict their binding potential against both isoforms of hERs or drug metabolizing enzymes such as (CYP) inhibition models. Our investigations revealed estrogenic character for most of the predicted metabolites and have confirmed earlier reports of potential CYP3A4 and CYP1A2 inhibition. Compilation of such data is essential to gain a better understanding of the efficacy/safety of licorice extracts used in various botanical formularies. This approach with the involved cheminformatic tools has proven effective to yield rich information to support our understanding of traditional practices. It also can expand the role of botanical drugs for introducing new chemical entities (NCEs) and/or uncovering their liabilities at early stages. In this work we endeavored to comprehend the mechanism associated with the efficacy and safety of components reported in the licorice plant. We utilized smart screening techniques such as cheminformatics tools to reveal the high number of secondary metabolites produced by licorice which are capable of interfering with the human Estrogen Receptors (hERs) and/or PXR or other vital cytochrome P450 enzymes. The genus Glycyrrhiza encompasses several species exhibiting complex structural diversity of secondary metabolites and hence biological activities. The intricate nature of botanical remedies such as licorice rendered them obsolete for scientific research or medical industry. Understanding and finding the mechanisms of efficacy or safety for a plant-based therapy is very challenging yet it remains crucial and warranted. The licorice plant is known to have Selective Estrogen Receptor Modulatory effects (SERMs) with a spectrum of estrogenic and anti-estrogenic activities attributed to women’s health. On the contrary licorice extract was shown to induce pregnane xenobiotic receptor (PXR) which may manifest as a potential route for deleterious effects such as herb-drug interaction (HDI). While many studies attributed these divergent activities to a few classes of compounds such as liquiritigenin (a weak estrogenic SERM) or glycyrrhizin (weak PXR agonist) no attempt was made to characterize the complete set of compounds responsible for these divergent activities. A plethora of licorice components is undermined which might have the potential to be developed into novel phytoSERMS or to trigger undesirable adverse effects by altering drug metabolizing enzymes and thus pharmacokinetics. Thus we have ventured to synthesize a set of constitutional isomers of stilbenoids and DHS (archetypal of those found in licorice) with different prenylation patterns. Sixteen constitutional isomers of stilbenoids (M2-M10) and DHS (M12-M18) were successfully synthesized of which six of them (M8 M9 M14 M15 M17 and M18) were synthesized for the first time to be further tested and validated with cell-based methods for their estrogenic activities. We have unveiled a novel class of compounds which possess a strong PXR activation. These results which were in accord with the in silico prediction were observed for multiple synthesized prenylated stilbenoid and DHS by the luciferase reporter gene assay at µM concentrations. Moreover this activation was further validated by the six-fold increase in mRNA expression of Cytochrome P450 3A4 (CYP3A4) where three representative compounds (M7 M10 and M15) exceeded the activation fold of the positive control

Bridging the gap between intellectual capital models: an ancestry/chronology approach

Since the first coining of the term ‘intellectual capital’ (IC) in Stewart’s “Brainpower” article of 1991, IC has gained popularity and interest amongst researchers from different disciplines as a source of attaining and maintaining competitive advantages. The result of these disciplines (e.g. human resources, accounting, marketing and finance) feeding into the IC literature has been a dramatic increase in the number of IC models. The diversity of the models has given rise to different approaches for realising the value of IC, provided different taxonomies for classifying IC, and introduced different practices for managing, measuring and reporting IC. This variety has made it a challenge for organisations to select the appropriate model to systematically manage, measure and report their organisational knowledge. This paper visualises the roots of IC models in the literature by examining the foundations and principles on which they are based. Such a visualisation affords the opportunity to establish common bases for IC modelling in order to reduce the diversity between IC models and increase their practical applicability. These bases are: the tendency towards enhancing the taxonomy of IC, and the tendency towards establishing the practices of managing, measuring and reporting IC. The main contribution of this paper is three ancestry/chronology diagrams that visualise fifty-four IC models and the rationale behind their development, which in turn brings greater coherence to the literature on IC modelling and conceptualisation

Revamping established project procurement approaches to support BIM implementation

Purpose Previous studies have established to a great extent that regulatory frameworks and, in particular, procurement approaches – that are common in a particular context – have a major impact on the success of building information modelling (BIM) implementation in construction projects. Despite the close links between these two concepts, research on the effect of procurement approaches on BIM implementation is scarce. To address this gap, this paper aims to investigate the barriers that affect BIM implementation through the lens of procurement approaches. Design/methodology/approach A mixed-method approach was adopted using a questionnaire survey (n = 116) and interviews with key stakeholders (n = 12) in Jordan. The outcomes of the quantitative parts were augmented with findings from interviews. Findings It was revealed that the deployment of unfavourable construction procurement approaches represents a major hurdle towards BIM implementation. Though essential for enhancing BIM implementation, it is revealed that a fundamental change from the common design-bid-build (DBB) to more collaborative procurement approaches remains infeasible in view of the realities that govern the construction industry. Research limitations/implications It was revealed the deployment of unfavourable construction procurement approaches represents a major hurdle towards BIM implementation. Though essential for enhancing BIM implementation, it is revealed that a fundamental change from the common DBB to more collaborative procurement approaches remains infeasible given the realities that govern the construction industry. Originality/value As the first of its kind, a set of recommendations for establishing supportive, workable procurement that does not deviate significantly from common procedures and practices is presented. Rather than advocating a shift to procurement approaches that are aligned with BIM, the findings offer novel insight into the necessity of developing a framework within the boundaries of the current and widely adopted procurement approaches to address the identified construction procurement issues and facilitate BIM implementation

Benefits of Implementing Occupational Health and Safety Management Systems for the Sustainable Construction Industry: A Systematic Literature Review

Accidents are more prevalent in the construction industry compared to other economic sectors. Therefore, understanding the benefits of occupational health and safety management systems (OHSMSs) in terms of their sustainable implementation, management and performance, as well as the awareness of OHMSs and barriers to their implementation, are important for improving OHSMSs in the sustainability of the construction industry. Although there is considerable research on OHSMSs, further assessments are needed concerning other aspects of OHSMSs, particularly the benefits of OHSMSs. Thus, this review paper summarises the empirical state of the art of OHSMS activities. Scopus, Web of Science and other databases were searched using predefined standards. The query was limited to articles published from 1999 to 2023. Consequently, one hundred and four articles were selected and analysed. These articles present analyses of OHSMSs and their potential benefits concerning the implementation of OHSMSs and management, performance, awareness, and barriers in relation to OHSMSs. The results reveal that 12.50% of the reviewed studies assessed the implementation of OHSMSs in the construction industry, and 25.96% studied the management of OHSMSs. Analyses of the performance of OHSMSs in the construction industry accounted for 8.65%, analyses of the awareness of OHSMSs accounted for 4.81%, model-related analyses accounted for 13.46%, studies on the significance/benefits of OHSMSs accounted for 3.85%, studies on the barriers/challenges associated with OHSMSs accounted for 5.77%, analyses on the safety indicators of OHSMSs accounted for 2.88% and other types of studies accounted for 20.19%. This study further reveals that the implementation of OHSMSs is characterised by a dearth of proper communication, the non-utilisation of personal protective equipment (PPE), wrong postures and work activities, a dearth of training, physiological factors including burnout and stress, and a dearth of safety culture and orientation; in addition, matters relating to compliance with effective laws are significant safety challenges in the construction industry. However, the rationality for evaluating the benefits of OHSMSs, comprising their implementation, management and performance, as well as awareness of and barriers to OHSMSs, is challenging to authenticate because appropriate field, survey, organisational and clinical data concerning incident occurrences in the construction industry are lacking for comprehensive evaluations. Thus, this novel study presents our effort to narrow this gap by establishing a framework for increasing our understanding of the benefits of implementing OHSMSs and accident reduction

Phenethyisoquinoline alkaloids from the leaves of Androcymbium palaestinum

Thirteen compounds were isolated from the methanolic extract of the leaves of Androcymbium palaestinum Baker (Colchicaceae). Of these, three were new, two were new natural products, and eight were known. The new isolated compounds were (+)-1-demethylandrocine (5), (−)-andropalaestine (8), and (+)-2-demethyl-β-lumicolchicone (10), while the new natural products were (+)-O-methylkreysigine-N-oxide (3) and (+)-O,O-dimethylautumnaline (9). Moreover, two known compounds are reported for the first time from this species, specifically (−)-colchicine (11) and (−)-3-demethyldemecolcine (13). The structures of the isolated compounds were elucidated using a series of spectroscopic and spectrometric techniques, principally HRESIMS, 1D-NMR (1H and 13C NMR) and 2D-NMR (COSY, edited-HSQC, and HMBC). ECD spectroscopy was used for assigning the absolute configurations of compounds 3, 5, and 10. The cytotoxic activities of the isolated compounds were evaluated using the MDA-MB-435 (melanoma), MDA-MB-231 (breast), and OVCAR3 (ovary) cancer cell lines. Compound 11 was the most potent against all tested cell lines, with IC50 values of 12, 95 and 23 nM, respectively.This research was supported, in part, by the Deanship of Research, Jordan University of Science and Technology, Irbid, Jordan (Grant No. 258/2017) and the National Cancer Institute/National Institutes of Health, Bethesda, MD, USA via P01 CA125066. We thank Dr. L. Flores Bocanegra, J. M. Gallagher, Z. Y. Al Subeh, and Dr. N. D. Paguigan from UNCG for technical help and valuable suggestions. This work was performed in part at the Joint School of Nanoscience and Nanoengineering, a member of the Southeastern Nanotechnology Infrastructure Corridor (SENIC) and National Nanotechnology Coordinated Infrastructure (NNCI), which is supported by the National Science Foundation (Grant ECCS-1542174)

Designing an intellectual capital framework for newspapers: the case of Jordan

Designing an intellectual capital framework for newspapers: the case of Jorda