• Title/Summary/Keyword: New Jersey State

Search Result 86, Processing Time 0.028 seconds

Drosophila melanogaster as a Model for Studying Aspergillus fumigatus

  • AL-Maliki, Hadeel Saeed;Martinez, Suceti;Piszczatowski, Patrick;Bennett, Joan W.
    • Mycobiology
    • /
    • v.45 no.4
    • /
    • pp.233-239
    • /
    • 2017
  • Drosophila melanogaster is a useful model organism that offers essential insights into developmental and cellular processes shared with humans, which has been adapted for large scale analysis of medically important microbes and to test the toxicity of heavy metals, industrial solvents and other poisonous substances. We here give a brief review of the use of the Drosophila model in medical mycology, discuss the volatile organic compounds (VOCs) produced by the opportunistic human pathogen, Aspergillus fumigatus, and give a brief summary of what is known about the toxicity of some common fungal VOCs. Further, we discuss the use of VOC detection as an indirect indicator of fungal growth, including for early diagnosis of aspergillosis. Finally, we hypothesize that D. melanogaster has promise for investigating the role of VOCs synthesized by A. fumigatus as possible virulence factors.

Differential Expression and Stability of Endogenous Nuclear Factor E2-related Factor 2 (Nrf2) by Natural Chemopreventive Compounds in HepG2 Human Hepatoma Cells

  • Jeong, Woo-Sik;Keum, Young-Sam;Chen, Chi;Jain, Mohit R.;Shen, Guoxiang;Kim, Jung-Hwan;Li, Wenge;Kong, Ah-Ng Tony
    • BMB Reports
    • /
    • v.38 no.2
    • /
    • pp.167-176
    • /
    • 2005
  • Nuclear factor-E2-related factor 2 (Nrf2) is known as a key regulator of ARE-mediated gene expression and the induction of Phase II detoxifying enzymes and antioxidant enzymes, which is also a common property of many chemopreventive agents. In the present study, we investigated the regulatory role of different chemopreventive agents including sulforaphane (SUL), allyl isothiocyanate (AITC), indole-3-carbinol (I3C), and parthenolide (PTL), in the expression and degradation of Nrf2 and the induction of the antioxidant enzyme HO-1. SUL strongly induced Nrf2 protein expression and ARE-mediated transcription activation, retarded degradation of Nrf2 through inhibiting Keap1, and thereby activating the transcriptional expression of HO-1. AITC was also a potent inducer of Nrf2 protein expression, ARE-reporter gene and HO-1 but had little effect on delaying the degradation of Nrf2 protein. Although PTL and I3C could induce ARE reporter gene expression and Nrf2 to some extent, they were not as potent as SUL and AITC. However, PTL dramatically induced the HO-1 expression, which was comparable to SUL, while I3C had no effect. In addition, when treated with SUL and PTL, inhibition of proteasome by MG132 did not cause additional accumulation of Nrf2, suggesting the involvement of other degradation mechanism(s) in the presence of these compounds such as SUL and PTL. In summary, the results of our current study indicated that different chemopreventive compounds have different regulatory properties on the accumulation and degradation of Nrf2 as well as the induction of cellular antioxidant enzyme HO-1.

In vivo Pharmacokinetics, Activation of MAPK Signaling and Induction of Phase II/III Drug Metabolizing Enzymes/Transporters by Cancer Chemopreventive Compound BHA in the Mice

  • Hu, Rong;Shen, Guoxiang;Yerramilli, Usha Rao;Lin, Wen;Xu, Changjiang;Nair, Sujit;Kong, Ah-Ng Tony
    • Archives of Pharmacal Research
    • /
    • v.29 no.10
    • /
    • pp.911-920
    • /
    • 2006
  • Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

Regulation of Nrf2 Transactivation Domain Activity by p160 RAC3/SRC3 and Other Nuclear Co-Regulators

  • Lin, Wen;Shen, Guoxiang;Yuan, Xiaoling;Jain, Mohit R.;Yu, Siwang;Zhang, Aihua;Chen, J. Don;Kong, Ah-Ng Tony
    • BMB Reports
    • /
    • v.39 no.3
    • /
    • pp.304-310
    • /
    • 2006
  • Transcription factor NF-E2-related factor 2 (Nrf2) regulates the induction of Phase II detoxifying enzymes and antioxidant enzymes in response to many cancer chemopreventive compounds. In this study, we investigated the role of receptor associated coactivator (RAC3) or steroid receptor coactivator-3 (SRC3) and other nuclear co-regulators including CBP/p300 (CREB-binding protein), CARM1 (Coactivator-associated arginine methyltransferase), PRMT1 (Protein arginine methyl-transferase 1), and p/CAF (p300/CBP-associated factor) in the transcriptional activation of a chimeric Gal4-Nrf2-Luciferase system containing the transactivation domain (TAD) of Nrf2 in HepG2 cells. The results indicated that RAC3 up-regulated the transactivation activity of Gal4-Nrf2-(1-370) in a dose-dependent manner. The enhancement of transactivation domain activity of Gal4-Nrf2-(1-370) by RAC3 was dampened in the presence of dominant negative mutants of RAC3. Next we studied the effects of other nuclear co-regulators including CBP/p300, CARM1, PRMT1 and p/CAF, and the results showed that they had different level of positive effects on this transactivation domain activity of Gal4-Nrf2-(1-370). But importantly, synergistic effects of these co-regulators in the presence of RAC3/SRC3 on the transactivation activity of Gal4-Nrf2-(1-370) were observed. In summary, our present study showed for the first time that the 160 RAC3/SRC3 is involved in the functional transactivation of TAD of Nrf2 and that the other nuclear co-regulators such as CBP/p300, CARM1, PRMT1 and p/CAF can also transcriptionally activate this TAD of Nrf2 and that they could further enhance the transactivation activity mediated by RAC3/SRC3.

Creep and Shrinkage of High Performance/High Strength Concrete

  • Suksawang, N.;Nassif, H.;Mohamed, A.;Hwang, Eui-Seung
    • Proceedings of the Korea Concrete Institute Conference
    • /
    • 2006.05b
    • /
    • pp.529-532
    • /
    • 2006
  • This paper presents results from creep and shrinkage tests performed on different High Strength Concrete (HSC) mixes (with compressive strengths up to 90 MPa). Results were compared with those from various Code prediction models. The effects of pozzolanic materials on the creep and shrinkage were also investigated. Results show that while fly ash increases the compressive creep of concrete, silica fume decreases it. Moreover, current creep and shrinkage prediction models need to be revised for the HSC mixture.

  • PDF

Performance Analysis of an ATM MUX with a New Space Priority Mechanism under ON-OFF Arrival Processes

  • Bang, Jongho;Ansari, Nirwan;Tekinay, Sirin
    • Journal of Communications and Networks
    • /
    • v.4 no.2
    • /
    • pp.128-135
    • /
    • 2002
  • We propose a new space priority mechanism, and analyze its performance in a single Constant Bit Rate (CBR) server. The arrival process is derived from the superposition of two types of traffics, each in turn results from the superposition of homogeneous ON-OFF sources that can be approximated by means of a two-state Markov Modulated Poisson Process (MMPP). The buffer mechanism enables the Asynchronous Transfer Mode (ATM) layer to adapt the quality of the cell transfer to the Quality of Service (QoS) requirements and to improve the utilization of network resources. This is achieved by "Selective-Delaying and Pushing-ln"(SDPI) cells according to the class they belong to. The scheme is applicable to schedule delay-tolerant non-real time traffic and delay-sensitive real time traffic. Analytical expressions for various performance parameters and numerical results are obtained. Simulation results in term of cell loss probability conform with our numerical analysis.

Modulation of Activator Protein-1 (AP-1) and MAPK Pathway by Flavonoids in Human Prostate Cancer PC3 Cells

  • Gopalakrishnan, Avanthika;Xu, Chang-Jiang;Nair, Sujit S.;Chen, Chi;Hebbar, Vidya;Kong, Ah-Ng Tony
    • Archives of Pharmacal Research
    • /
    • v.29 no.8
    • /
    • pp.633-644
    • /
    • 2006
  • In last couple of decades the use of natural compounds like flavonoids as chemopreventive agents has gained much attention. Our current study focuses on identifying chemopreventive flavonoids and their mechanism of action on human prostate cancer cells. Human prostate cancer cells (PC3), stably transfected with activator protein 1 (AP-1) luciferase reporter gene were treated with four main classes of flavonoids namely flavonols, flavones, flavonones, and isoflavones. The maximum AP-1 luciferase induction of about 3 fold over control was observed with $20\;{\mu}M$ concentrations of quercetin, chrysin and genistein and $50\;{\mu}M$ concentration of kaempferol. At higher concentrations, most of the flavonoids demonstrated inhibition of AP-1 activity. The MTS assay for cell viability at 24 h showed that even at a very high concentration $(500\;{\mu}M)$, cell death was minimal for most of the flavonoids. To determine the role of MAPK pathway in the induction of AP-1 by flavonoids, Western blot of phospho MAPK proteins was performed. Four out of the eight flavonoids namely kaempferol, apigenin, genistein and naringenin were used for the Western Blot analysis. Induction of phospho-JNK and phospho-ERK activity was observed after two hour incubation of PC3-AP1 cells with flavonoids. However no induction of phospho-p38 activity was observed. Furthermore, pretreating the cells with specific inhibitors of JNK reduced the AP-1 luciferase activity that was induced by genistein while pretreatment with MEK inhibitor reduced the AP-1 luciferase activity induced by kaempferol. The pharmacological inhibitors did not affect the AP-1 luciferase activity induced by apigenin and naringenin. These results suggest the possible involvement of JNK pathway in genistein induced AP-1 activity while the ERK pathway seems to play an important role in kaempferol induced AP-1 activity.

Health Effects of Small Volatile Compounds from East Asian Medicinal Mushrooms

  • Pennerman, Kayla K.;Yin, Guohua;Bennett, Joan Wennstrom
    • Mycobiology
    • /
    • v.43 no.1
    • /
    • pp.9-13
    • /
    • 2015
  • Medicinal fungi, taken whole or as various forms of extracts, have been used to alleviate, cure or prevent human ailments since pre-historic times. In particular, Asian cultures have incorporated a variety of mushrooms into their medical practices. Chemically pure, bioactive metabolites from fungi have been a mainstay of modern pharmacological research and in addition to antibiotics, include anticancer agents, immunosuppressants, enzyme inhibitors, antagonist and agonists of hormones, and a variety of psychotropic substances. However, to date not many studies have focused on the possible health benefits of odorant volatile organic compounds (i.e., gas phase compounds). An analysis of these compounds for their health related effects will expand the range of compounds available for the treatment of chronic and acute diseases. This review highlights phenolic acids and monoterpenes from Asian medicinal mushrooms (AMMs), which not only produce pleasant odors but also have antioxidant and antibacterial effects. Odorant bioactive volatile phase compounds from medicinal mushrooms remain an essentially untapped source for future medicines, and AMMs remain a promising resource for future pharmacological research.