Creating Subnetworks from Transcriptomic Data on Central Nervous System Diseases Informed by a Massive Transcriptomic Network

Feng, Yaping,Syrkin-Nikolau, Judith A.,Wurtele, Eve S. Korean Society for Bioinformatics 2013 Interdisciplinary Bio Central (IBC) Vol.5 No.1

High quality publicly-available transcriptomic data representing relationships in gene expression across a diverse set of biological conditions is used as a context network to explore transcriptomics of the CNS. The context network, 18367Hu-matrix, contains pairwise Pearson correlations for 22,215 human genes across18,637 human tissue samples1. To do this, we compute a network derived from biological samples from CNS cells and tissues, calculate clusters of co-expressed genes from this network, and compare the significance of these to clusters derived from the larger 18367Hu-matrix network. Sorting and visualization uses the publicly available software, MetaOmGraph (http://www.metnetdb.org/MetNet_MetaOm-Graph.htm). This identifies genes that characterize particular disease conditions. Specifically, differences in gene expression within and between two designations of glial cancer, astrocytoma and glioblastoma, are evaluated in the context of the broader network. Such gene groups, which we term outlier-networks, tease out abnormally expressed genes and the samples in which this expression occurs. This approach distinguishes 48 subnetworks of outlier genes associated with astrocytoma and glioblastoma. As a case study, we investigate the relationships among the genes of a small astrocytoma-only subnetwork. This astrocytoma-only subnetwork consists of SVEP1, IGF1, CHRNA3, and SPAG6. All of these genes are highly coexpressed in a single sample of anaplastic astrocytoma tumor (grade III) and a sample of juvenile pilocytic astrocytoma. Three of these genes are also associated with nicotine. This data lead us to formulate a testable hypothesis that this astrocytoma outlier-network provides a link between some gliomas/astrocytomas and nicotine.

Identification and biosynthesis of acylphloroglucinols in <i>Hypericum gentianoides</i>

Crispin, Matthew C.,Hur, Manhoi,Park, Taeseong,Kim, Young Hwan,Wurtele, Eve Syrkin Blackwell Publishing Ltd 2013 Physiologia Plantarum Vol.148 No.3

<P>Species of the genus <I>Hypericum</I> contain a rich array of unusual polyketides, however, only a small proportion of the over 450 <I>Hypericum</I> species, other than the popular medicinal supplement St. John's Wort (<I>Hypericum perforatum</I>), have even been chemically characterized. <I>Hypericum gentianoides</I>, a small annual used medicinally by Cherokee Americans, contains bioactive acylphloroglucinols. Here, we identify acylphloroglucinol constituents of <I>H. gentianoides</I> and determine a potential pathway to their synthesis. Liquid chromatography/electrospray ionization‐mass spectrometry (LC/ESI‐MS) and HPLC‐UV indicate that the level of accumulation and profile of acylphloroglucinols in <I>H. gentianoides</I> vary little seasonally when grown in a greenhouse, but do vary with development and are highly dependent on the accession, highlighting the importance of the selection of plant material for study. We identify the chemical structures of the nine prevalent polyketides, based on LC/ESI‐MS and hybrid quadrupole orthogonal time‐of‐flight (Q‐TOF) mass spectrometry; these metabolites include one monomeric phlorisobutyrophenone (PIB) derivative and eight dimeric acylphloroglucinols. Q‐TOF spectrometry was used to identify eight additional PIB derivatives that were not detected by LC/ESI‐MS. These data lead us to propose that diacylphloroglucinols are synthesized via modification of PIB to yield diverse phloroglucinol and filicinic acids moieties, followed by dimerization of a phloroglucinol and a filicinic acid monomer to yield the observed complement of diacylphloroglucinols. The metabolomics data from <I>H. gentianoides</I> are accessible in plant metabolomics resource (PMR) (<url href='http://www.metnetdb.org/pmr'>http://www.metnetdb.org/pmr), a public metabolomics database with analysis software for plants and microbial organisms.</P>

Enhancement of Innate and Adaptive Immune Functions by Multiple Echinacea Species

Zili Zhai,Yi Liu,Lankun Wu,David S. Senchina,Eve S. Wurtele,Patricia A. Murphy,Marian L. Kohut,Joan E. Cunnick 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.3

Echinaceapreparations are commonly used as nonspecific immunomodulatory agents. Alcohol extracts fromthree widely used Echinaceaspecies, Echinacea angustifolia, Echinacea pallida, and Echinacea purpurea, were investigatedfor immunomodulating properties. The three Echinaceaspecies demonstrated a broad difference in concentrations of indi-vidual lipophilic amides and hydrophilic caffeic acid derivatives. Mice were gavaged once a day (for 7 days) with one of theEchinaceaextracts (130 mg/kg) or vehicle and immunized with sheep red blood cells (sRBC) 4 days prior to collection ofimmune cells for multiple immunological assays. The three herb extracts induced similar, but differential, changes in the per-centage of immune cell populations and their biological functions, including increased percentages of CD49. and CD19.lymphocytes in spleen and natural killer cell cytotoxicity. Antibody response to sRBC was significantly increased equally byextracts of all three Echinacea species. Concanavalin A-stimulated splenocytes from E. angustifolia- and E. pallida-treatedmice demonstrated significantly higher T cell proliferation. In addition, the Echinaceatreatment significantly altered the cy-tokine production by mitogen-stimulated splenic cells. The three herbal extracts significantly increased interferon-. produc-tion, but inhibited the release of tumor necrosis factor-. and interleukin (IL)-1.. Only E. angustifolia- and E. pallida-treatedmice demonstrated significantly higher production of IL-4 and increased IL-10 production. Taken together, these findingsdemonstrated that Echinaceais a wide-spectrum immunomodulator that modulates both innate and adaptive immune responses.In particular, E. angustifoliaor E. pallidamay have more anti-inflammatory potential.

Evaluation of the Polyphenol Content and Antioxidant Properties of Methanol Extracts of the Leaves, Stem, and Root Barks of Moringa oleifera Lam.

Sunday E. Atawodi,Joy C. Atawodi,Gabriel A. Idakwo,Beate Pfundstein,Roswitha Haubner,Gerd Wurtele,Helmut Bartsch,Robert W. Owen 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.3

Medicinal plants have been shown to have both chemopreventive and/or therapeutic effects on cancer and other diseases related to oxidative damage. Moringa oleifera Lam., known in the Hausa and Igala languages of Nigeria as “Zogale” and “Gergedi,” respectively, and drumstick in English, is a plant that is used both as food and in folkloric medicine in Nigeria and elsewhere. Different parts of the plant were analyzed for polyphenol content as well as in vitro antioxidant potential. The methanol extract of the leaves of M. oleifera contained chlorogenic acid, rutin, quercetin glucoside, and kaempferol rhamnoglucoside, whereas in the root and stem barks, several procyanidin peaks were detected. With the xanthine oxidase model system, all the extracts exhibited strong in vitro antioxidant activity, with 50% inhibitory concentration (IC50) values of 16, 30, and 38μL for the roots, leaves, and stem bark, respectively. Similarly, potent radical scavenging capacity was observed when extracts were evaluated with the 2-deoxyguanosine assay model system, with IC50 values of 40, 58, and 72μL for methanol extracts of the leaves, stem, and root barks, respectively. The high antioxidant/radical scavenging effects observed for different parts of M. oleifera appear to provide justification for their widespread therapeutic use in traditional medicine in different continents. The possibility that this high antioxidant/radical scavenging capacity may impact on the cancer chemopreventive potential of the plant must be considered.

Evaluation of the Polyphenol Composition and Antioxidant Activity of African Variety of Dacryodes edulis (G.Don) H.J Lam Fruit

S.E. Atawodi,J.C. Atawodi,P. Idakwo,B. Pfundstein,R. Haubner,G. Wurtele,B. Spiegelhalder,H. Bartsch,R.W. Owen 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.6

Polyphenols are abundant micronutrients in our diet that have been credited with chemoprevention of diseases associated with oxidative stress. In this study, we investigated the whole ripened fruit of Dacryodes edulis (G.Don) H.J Lam, a multipurpose tree growing in West and Central Africa and other countries bordering the Gulf of Guinea, for polyphenol content as well as its antioxidant/radical scavenging capacity. Analysis of the methanol extract of the fruit by high-performance liquid chromatography coupled to an ultraviolet dual-array detector and mass-selective detector revealed the presence of catechol (9.27mg/kg), gallate (10.40mg/kg), methylgallate (0.88mg/kg), ellagic acid (3.10mg/kg), quercetin (0.21mg/kg), and quercetin rhamnoside (0.76mg/kg). The extract showed very high antioxidant potential (50% inhibitory concentration [IC50]=14μL), but a rather weak radical scavenging activity (IC50=357μL), when tested in vitro with the xanthine oxidase and 2-deoxyguanosine assay model systems, respectively. These results suggest that consumption of D. edulis could contribute to prevention of diseases that are related to oxidative stress.

Polyphenol Composition and Antioxidant Potential of Hibiscus esculentus L. Fruit Cultivated in Nigeria

S.E. Atawodi,J.C. Atawodi,G.A. Idakwo,B. Pfundstein,R. Haubner,G. Wurtele,B. Spiegelhalder,H. Bartsch,R.W. Owen 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.6

Consumption of certain fruits and vegetables is now widely associated with chemoprevention of degenerative diseases like cancer and cardiovacsular disorders because of their antioxidant components. Polyphenols, a heterogeneous group of compounds, are one of these constituents. Hibiscus esculentus L. (Family Malvaceae), commonly referred to as okro, okra, or lady's finger, is an important component of diet in Nigeria and other countries in sub-Saharan Africa. In this article, we describe the polyphenol composition and antioxidant potential of H. esculentus of Nigerian origin. Quercetin glucoside (quercetrin) and an unidentified flavonoid were detected. In vitro antioxidant assay of methanol extract of the fruits showed potent antioxidant/radical scavenging activities with 50% inhibitory concentration values of 25 and 43μL when analyzed by the xanthine oxidase and 2-deoxyguanosine methods, respectively. These data suggest that H. esculentus, popular especially during the rainy season in Nigeria and many tropical West, Central, and Eastern African countries, is a good contributor to the antioxidant status and disease chemoprevention of people in these countries.

Patterns of Metabolite Changes Identified from Large-Scale Gene Perturbations in Arabidopsis Using a Genome-Scale Metabolic Network

Kim, Taehyong,Dreher, Kate,Nilo-Poyanco, Ricardo,Lee, Insuk,Fiehn, Oliver,Lange, Bernd Markus,Nikolau, Basil J.,Sumner, Lloyd,Welti, Ruth,Wurtele, Eve S.,Rhee, Seung Y. American Society of Plant Biologists 2015 Plant Physiology Vol.167 No.4

<P><I>Global patterns of metabolic responses upon single gene perturbations are specific to gene functions, but they are coordinated with characteristics of the perturbed genes.</I></P><P>Metabolomics enables quantitative evaluation of metabolic changes caused by genetic or environmental perturbations. However, little is known about how perturbing a single gene changes the metabolic system as a whole and which network and functional properties are involved in this response. To answer this question, we investigated the metabolite profiles from 136 mutants with single gene perturbations of functionally diverse Arabidopsis (<I>Arabidopsis thaliana</I>) genes. Fewer than 10 metabolites were changed significantly relative to the wild type in most of the mutants, indicating that the metabolic network was robust to perturbations of single metabolic genes. These changed metabolites were closer to each other in a genome-scale metabolic network than expected by chance, supporting the notion that the genetic perturbations changed the network more locally than globally. Surprisingly, the changed metabolites were close to the perturbed reactions in only 30% of the mutants of the well-characterized genes. To determine the factors that contributed to the distance between the observed metabolic changes and the perturbation site in the network, we examined nine network and functional properties of the perturbed genes. Only the isozyme number affected the distance between the perturbed reactions and changed metabolites. This study revealed patterns of metabolic changes from large-scale gene perturbations and relationships between characteristics of the perturbed genes and metabolic changes.</P>