1,525 research outputs found

    A Novel Mechanism of PPARĪ³ Regulation of TGFĪ²1: Implication in Cancer Biology

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    Peroxisome proliferator-activated receptor-Ī³ (PPARĪ³) and retinoic acid X-receptor (RXR) heterodimer, which regulates cell growth and differentiation, represses the TGFĪ²1 gene that encodes for the protein involved in cancer biology. This review will introduce the novel mechanism associated with the inhibition of the TGFĪ²1 gene by PPARĪ³ activation, which regulates the dephosphorylation of Zf9 transcription factor. Pharmacological manipulation of TGFĪ²1 by PPARĪ³ activators can be applied for treating TGFĪ²1-induced pathophysiologic disorders such as cancer metastasis and fibrosis. In this article, we will discuss the opposing effects of TGFĪ² on tumor growth and metastasis, and address the signaling pathways regulated by PPARĪ³ for tumor progression and suppression

    Nicotiana benthamiana protein, NbPCIP1, interacting with Potato virus X coat protein plays a role as susceptible factor for viral infection

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    AbstractThe interactions of viral coat protein (CP) and host factors play an important role in viral replication and/or host defense mechanism. In this study, we constructed Nicotiana benthamiana cDNA library to find host factors interacting with Potato virus X (PVX) CP. Using yeast two-hybrid assay, we screened 3.3Ɨ106 independent yeast transformants from N. benthamiana cDNA library and identified six positive clones. One positive clone, named PVX CP-interacting protein 1 (NbPCIP1), is a plant-specific protein with homologue in N. tabacum (GenBank accession no. AB04049). We confirmed the PVX CPā€“NbPCIP1 interaction using yeast-two hybrid assay in yeast, proteinā€“protein binding assay in vitro, and bimolecular fluorescent complementation assay in planta. Quantitative real-time RT-PCR analysis showed that the mRNA level of NbPCIP1 increased in PVX-infected N. benthamiana plants as compared to that of healthy plants. The green fluorescent protein (sGFP)-fused NbPCIP1 (NbPCIP1-sGFP) was localized in ER or ER-associated granular-like structure of cells. When we co-express NbPCIP1-sGFP and red fluorescent protein (RFP)-fused PVX CP (PVX CP-RFP), which were introduced by transiently expressing these proteins in N. benthamiana protoplasts and epidermal cells, however, we observed the co-localization of these proteins in the inclusion body-like complex in areas surrounding nucleus. Transient over-expression and transgene silencing of NbPCIP1 assay analysis indicated that NbPCIP1 plays a critical role in viral replication during PVX infection in host plant

    Development of a high yield purification process for the production of influenza virus vaccines

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    Production of influenza virus in animal cells has emerged as an alternative to conventional platforms such as egg-based production system. Animal cells, especially MDCK and VERO cell lines, are widely used as the primary production cell for influenza virus vaccine because of their high susceptibility to infection with various influenza viruses. Recently, a robust and reliable purification process was successfully developed for the production of quadri-valent HA proteins (from two strains of the type A virus and two strains of the type B virus) by using animal cell-based production system in Green Cross Corp., Korea. The UF/DF process, Benzonase treatment at high temperature as well as column chromatography strategy was optimized to maximize the final HA production yields. Benzonase treatment was conducted to reduce in hcDNA (host cell DNA) because hcDNA was main impurity for cell-based influenza virus vaccine. A simple and stable UF/DF process has been tested with membrane molecular weight cutoffs of 100 and 300 kDa as well as 0.2 and 0.45 um microfiltration membrane. Anion exchange chromatography (AEC) and size exclusion chromatography (SEC) were selected for acceptable reduction in hcDNA and HCP. AEC was used to separate hcDNA from virus at a salt concentration of 0.5 M sodium chloride. The HA yield through AEC & SEC combination process was sufficiently achieved under specific purification process condition. Overall, the amount of residual hcDNA was reduced to an acceptable level (10ng/dose) and the increased HA yield was maintained throughout the whole process. The performance, productivity and scalability of the purification process were successfully demonstrated in over 30 GMP batches using 4 different influenza virus strains

    Synergistic Uric Acid-Lowering Effects of the Combination of Chrysanthemum indicum

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    Chrysanthemum indicum Linne flower (CF) and Cinnamomum cassia (L.) J. Persl bark (CB) extracts have served as the main ingredients in several prescriptions designed to treat hyperuricemia and gout in traditional Chinese and Korean medicine. However, little is known about the combination effects of a CF and CB (CC) mixture on hyperuricemia. In our study, we investigated the antihyperuricemic effects of CC mixture and the mechanisms underlying these effects in normal and potassium oxonate- (PO-) induced hyperuricemic rats. The CC mixture significantly decreased uric acid levels in normal and PO-induced hyperuricemic rats and showed the enhanced hypouricemic effect compared to CF or CB alone. Furthermore, the CC mixture increased renal uric acid excretion in PO-induced hyperuricemic rat. We found that CC mixture and its major components, chlorogenic acid, 3,4-dicaffeoylquinic acid (isochlorogenic acid), coumarin, cinnamaldehyde, trans-cinnamic acid, and o-methoxycinnamaldehyde, inhibit the activity of xanthine oxidase (XOD) in vitro. The CC mixture exerts antihyperuricemic effects accompanied partially by XOD activity inhibition. Therefore, the CC mixture may have potential as a treatment for hyperuricemia and gout

    Nitric oxide induces MUC5AC mucin in respiratory epithelial cells through PKC and ERK dependent pathways

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    BACKGROUND: Nitric oxide (NO) is generally increased during inflammatory airway diseases. This increased NO stimulates the secretion of mucin from the goblet cell and submucosal glands but the mechanism is still unknown precisely. In this study, we investigated potential signaling pathways involving protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) in the NO-induced MUC5AC mucin gene and protein expression in A549 cells. METHODS: Nitric oxide was donated to the A549 cells by NOR-1. MUC5AC mucin levels were assayed by enzyme-linked immunosorbent assay (ELISA). MUC5AC promoter activity was determined by measuring luciferase activity after the lysing the transfected cells. Activation of PKC isoforms were measured by assessing the distribution of the enzyme between cytosolic and membrane fractions using immunoblotting. Immunoblotting experiments using a monoclonal antibody specific to PKC isoforms were performed in the cytosol and membrane fractions from A549 cells. Western blot analysis for pERK and p38 were performed using the corresponding antibodies from the cell lysates after donating NO to the A549 cells by NOR-1. RESULTS: The transcriptional activity of MUC5AC promoter was maximal at the concentration of 0.1 mM NOR-1 for 1 hour incubation in transfected A549 cells. (Ā±)-(E)-methyl-2-((E)-hydroxyimino)-5-nitro-6-methoxy-3-hexenamide (NOR-1) markedly displaced the protein kinase C (PKC)Ī± and PKCĪ“ from the cytosol to the membrane. Furthermore, the PKC-Ī±,Ī²inhibitors, GƖ6976 (10 nM) and PKCĪ“ inhibitors, rottlerin (4 Ī¼M) inhibited the NOR-1 induced migration of PKCĪ± and PKCĪ“ respectively. NOR-1 also markedly increased the MUC5AC promoter activity and mRNA expression, mucin synthesis and ERK1/2 phosphorylation. The PKC inhibitors also inhibited the NOR-1 induced MUC5AC mRNA and MUC5AC protein synthesis by inhibiting the activation of PKCĪ± and PKCĪ“ with ERK1/2 pathways. CONCLUSION: Exogenous NO induced the MUC5AC mucin gene and protein through the PKCĪ± and PKCĪ“ ā€“ ERK pathways in A549 cells. Inhibition of PKC attenuated NO-mediated MUC5AC mucin synthesis. In view of this findings, PKC inhibitors might be useful in the treatment of bronchial asthma and chronic bronchitis patients where NO and mucus are increased in the bronchial airways

    Environmental and health impacts of using food waste as animal feed: a comparative analysis of food waste management options.

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    The disposal of food waste is a large environmental problem. In the United Kingdom (UK), approximately 15 million tonnes of food are wasted each year, mostly disposed of in landfill, via composting, or anaerobic digestion (AD). European Union (EU) guidelines state that food waste should preferentially be used as animal feed though for most food waste this practice is currently illegal, because of disease control concerns. Interest in the potential diversion of food waste for animal feed is however growing, with a number of East Asian states offering working examples of safe food waste recycling - based on tight regulation and rendering food waste safe through heat treatment. This study investigates the potential benefits of diverting food waste for pig feed in the UK. A hybrid, consequential life cycle assessment (LCA) was conducted to compare the environmental and health impacts of four technologies for food waste processing: two technologies of South Korean style-animal feed production (as a wet pig feed and a dry pig feed) were compared with two widespread UK disposal technologies: AD and composting. Results of 14 mid-point impact categories show that the processing of food waste as a wet pig feed and a dry pig feed have the best and second-best scores, respectively, for 13/14 and 12/14 environmental and health impacts. The low impact of food waste feed stems in large part from its substitution of conventional feed, the production of which has substantial environmental and health impacts. While the re-legalisation of the use of food waste as pig feed could offer environmental and public health benefits, this will require support from policy makers, the public, and the pig industry, as well as investment in separated food waste collection which currently occurs in only a minority of regions.E.K.H.J.zE was funded by BBSRC grant BB/J014540/1. R.S. was funded by the Islamic Development Bank and Cambridge Overseas Trust.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.jclepro.2016.05.04

    An Analysis of Location of Needle Entry Point and Palpated PSIS in S1 Nerve Root Block

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    BACKGROUND: The first sacral nerve root block (S1NRB) is a common procedure in pain clinic for patients complaining of low back pain with radiating pain. It can be performed in the office based setting without C-arm. The previously suggested method of locating the needle entry point begins with identifying the posterior superior iliac spine (PSIS). Then a line is drawn between two points, one of which is 1.5 cm medial to the PSIS, and the other of which is 1.5 cm lateral and cephalad to the ipsilateral cornu. After that, one point on the line, which is 1.5 cm cephalad to the level of the PSIS, is considered as the needle entry point. The purpose of this study was to analyze the location of needle entry point and palpated PSIS in S1NRB. METHODS: Fifty patients undergoing C-arm guided S1NRB in the prone position were examined. The surface anatomical relationships between the palpated PSIS and the needle entry point were assessed. RESULTS: The analysis revealed that the transverse and vertical distance between the needle entry point and PSIS were 28.7 Ā± 8.8 mm medially and 3.5 Ā± 14.0 mm caudally, respectively. The transverse distance was 27.8 Ā± 8.3 mm medially for male and 29.5 Ā± 9.3 mm medially for female. The vertical distance was 1.0 Ā± 14.1 mm cranially for male and 8.1 Ā± 12.7 mm caudally for female. CONCLUSIONS: The needle entry point in S1NRB is located on the same line or in the caudal direction from the PSIS in a considerable number of cases. Therefore previous recommended methods cannot be applied to many cases.ope
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