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Special Issue "Pharmaceuticals and Nutraceuticals by Molecular Farming"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 May 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Chang Won Choi (Website)

Department of Biology & Medicinal Science, Pai Chai University, 155-40 Baejae-ro, Seo-Gu, Daejeon 35345, Korea
Phone: +82-42-520-5617
Fax: +82-70-4362-6308
Interests: plant-derived biomedicines; plant-made pharmaceuticals; molecular farming; recombinant proteins; plant metabolic engineering; hypoglycaemic; hypolipidemic; antioxidants; antiviral

Special Issue Information

Dear Colleagues,

Molecular farming (MF), in terms of production scale and economy, product safety, ease of storage, and distribution, is superior to any other current commercial alternative. Despite MF’s promising benefits, the commercialization of MF-derived products is lagging behind due to uncertainty and safety issues. A particularly troubling issue concerns the adaptation of good manufacturing practice regulations for transgenic organisms. Although MF is not yet routinely commercialized, interest and investment in MF are extending rapidly. Ultimately, MF will progress and become a core commercial development in biotechnology.

This Special Issue aims to provide high quality research concerning novel gene expression in target organisms, MF’s industrial and preclinical/clinical applications, and MF’s environmental impacts. Possible topics cover research at both the basic and applied sciences levels, and concern yeast, fungi, algae, insects, plants, fish or mammals. Possible products include biopharmaceuticals, nutraceuticals, vaccines, metabolites, and proteins for industrial purposes. I wish to thank all authors for their contributions to this Special Issue.

Dr. Chang Won Choi
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs).


Keywords

  • molecular farming
  • transgenic organisms
  • industrial, preclinical/clinical applications
  • environmental impacts
  • yeast, fungi, algae, insects, plants, fish, mammals, biopharmaceuticals, nutraceuticals, vaccines, metabolites, proteins for industrial purposes

Related Special Issue

Published Papers (6 papers)

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Research

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Open AccessArticle Mycophenolate Antagonizes IFN-γ-Induced Catagen-Like Changes via β-Catenin Activation in Human Dermal Papilla Cells and Hair Follicles
Int. J. Mol. Sci. 2014, 15(9), 16800-16815; doi:10.3390/ijms150916800
Received: 20 June 2014 / Revised: 23 August 2014 / Accepted: 3 September 2014 / Published: 22 September 2014
Cited by 3 | PDF Full-text (1565 KB) | HTML Full-text | XML Full-text
Abstract
Recently, various immunosuppressant drugs have been shown to induce hair growth in normal hair as well as in alopecia areata and androgenic alopecia; however, the responsible mechanism has not yet been fully elucidated. In this study, we investigate the influence of mycophenolate [...] Read more.
Recently, various immunosuppressant drugs have been shown to induce hair growth in normal hair as well as in alopecia areata and androgenic alopecia; however, the responsible mechanism has not yet been fully elucidated. In this study, we investigate the influence of mycophenolate (MPA), an immunosuppressant, on the proliferation of human dermal papilla cells (hDPCs) and on the growth of human hair follicles following catagen induction with interferon (IFN)-γ. IFN-γ was found to reduce β-catenin, an activator of hair follicle growth, and activate glycogen synthase kinase (GSK)-3β, and enhance expression of the Wnt inhibitor DKK-1 and catagen inducer transforming growth factor (TGF)-β2. IFN-γ inhibited expression of ALP and other dermal papillar cells (DPCs) markers such as Axin2, IGF-1, and FGF 7 and 10. MPA increased β-catenin in IFN-γ-treated hDPCs leading to its nuclear accumulation via inhibition of GSK3β and reduction of DKK-1. Furthermore, MPA significantly increased expression of ALP and other DPC marker genes but inhibited expression of TGF-β2. Therefore, we demonstrate for the first time that IFN-γ induces catagen-like changes in hDPCs and in hair follicles via inhibition of Wnt/β-catenin signaling, and that MPA stabilizes β-catenin by inhibiting GSK3β leading to increased β-catenin target gene and DP signature gene expression, which may, in part, counteract IFN-γ-induced catagen in hDPCs. Full article
(This article belongs to the Special Issue Pharmaceuticals and Nutraceuticals by Molecular Farming)
Open AccessArticle Synergistic Effect of Combinatorial Treatment with Curcumin and Mitomycin C on the Induction of Apoptosis of Breast Cancer Cells: A cDNA Microarray Analysis
Int. J. Mol. Sci. 2014, 15(9), 16284-16301; doi:10.3390/ijms150916284
Received: 27 May 2014 / Revised: 19 August 2014 / Accepted: 3 September 2014 / Published: 15 September 2014
Cited by 6 | PDF Full-text (1347 KB) | HTML Full-text | XML Full-text
Abstract
In order to explore the synergistic mechanisms of combinatorial treatment using curcumin and mitomycin C (MMC) for breast cancer, MCF-7 breast cancer xenografts were conducted to observe the synergistic effect of combinatorial treatment using curcumin and MMC at various dosages. The synergistic [...] Read more.
In order to explore the synergistic mechanisms of combinatorial treatment using curcumin and mitomycin C (MMC) for breast cancer, MCF-7 breast cancer xenografts were conducted to observe the synergistic effect of combinatorial treatment using curcumin and MMC at various dosages. The synergistic mechanisms of combinatorial treatment using curcumin and MMC on the inhibition of tumor growth were explored by differential gene expression profile, gene ontology (GO), ingenuity pathway analysis (IPA) and Signal–Net network analysis. The expression levels of selected genes identified by cDNA microarray expression profiling were validated by quantitative RT-PCR (qRT-PCR) and Western blot analysis. Effect of combinatorial treatment on the inhibition of cell growth was observed by MTT assay. Apoptosis was detected by flow cytometric analysis and Hoechst 33258 staining. The combinatorial treatment of 100 mg/kg curcumin and 1.5 mg/kg MMC revealed synergistic inhibition on tumor growth. Among 1501 differentially expressed genes, the expression of 25 genes exhibited an obvious change and a significant difference in 27 signal pathways was observed (p < 0.05). In addition, Mapk1 (ERK) and Mapk14 (MAPK p38) had more cross-interactions with other genes and revealed an increase in expression by 8.14- and 11.84-fold, respectively during the combinatorial treatment by curcumin and MMC when compared with the control. Moreover, curcumin can synergistically improve tumoricidal effect of MMC in another human breast cancer MDA-MB-231 cells. Apoptosis was significantly induced by the combinatorial treatment (p < 0.05) and significantly inhibited by ERK inhibitor (PD98059) in MCF-7 cells (p < 0.05). The synergistic effect of combinatorial treatment by curcumin and MMC on the induction of apoptosis in breast cancer cells may be via the ERK pathway. Full article
(This article belongs to the Special Issue Pharmaceuticals and Nutraceuticals by Molecular Farming)
Open AccessArticle Expression of Aspergillus nidulans phy Gene in Nicotiana benthamiana Produces Active Phytase with Broad Specificities
Int. J. Mol. Sci. 2014, 15(9), 15571-15591; doi:10.3390/ijms150915571
Received: 7 February 2014 / Revised: 9 July 2014 / Accepted: 22 August 2014 / Published: 3 September 2014
PDF Full-text (2450 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A full-length phytase gene (phy) of Aspergillus nidulans was amplified from the cDNA library by polymerase chain reaction (PCR), and it was introduced into a bacterial expression vector, pET-28a. The recombinant protein (rPhy-E, 56 kDa) was overexpressed in the insoluble [...] Read more.
A full-length phytase gene (phy) of Aspergillus nidulans was amplified from the cDNA library by polymerase chain reaction (PCR), and it was introduced into a bacterial expression vector, pET-28a. The recombinant protein (rPhy-E, 56 kDa) was overexpressed in the insoluble fraction of Escherichia coli culture, purified by Ni-NTA resin under denaturing conditions and injected into rats as an immunogen. To express A. nidulans phytase in a plant, the full-length of phy was cloned into a plant expression binary vector, pPZP212. The resultant construct was tested for its transient expression by Agrobacterium-infiltration into Nicotiana benthamiana leaves. Compared with a control, the agro-infiltrated leaf tissues showed the presence of phy mRNA and its high expression level in N. benthamiana. The recombinant phytase (rPhy-P, 62 kDa) was strongly reacted with the polyclonal antibody against the nonglycosylated rPhy-E. The rPhy-P showed glycosylation, two pH optima (pH 4.5 and pH 5.5), an optimum temperature at 45~55 °C, thermostability and broad substrate specificities. After deglycosylation by peptide-N-glycosidase F (PNGase-F), the rPhy-P significantly lost the phytase activity and retained 1/9 of the original activity after 10 min of incubation at 45 °C. Therefore, the deglycosylation caused a significant reduction in enzyme thermostability. In animal experiments, oral administration of the rPhy-P at 1500 U/kg body weight/day for seven days caused a significant reduction of phosphorus excretion by 16% in rat feces. Besides, the rPhy-P did not result in any toxicological changes and clinical signs. Full article
(This article belongs to the Special Issue Pharmaceuticals and Nutraceuticals by Molecular Farming)
Open AccessArticle Resveratrol Induces the Expression of Interleukin-10 and Brain-Derived Neurotrophic Factor in BV2 Microglia under Hypoxia
Int. J. Mol. Sci. 2014, 15(9), 15512-15529; doi:10.3390/ijms150915512
Received: 15 May 2014 / Revised: 8 August 2014 / Accepted: 26 August 2014 / Published: 2 September 2014
Cited by 13 | PDF Full-text (5032 KB) | HTML Full-text | XML Full-text
Abstract
Microglia are the resident macrophages of the central nervous system (CNS) and play an important role in neuronal recovery by scavenging damaged neurons. However, overactivation of microglia leads to neuronal death that is associated with CNS disorders. Therefore, regulation of microglial activation [...] Read more.
Microglia are the resident macrophages of the central nervous system (CNS) and play an important role in neuronal recovery by scavenging damaged neurons. However, overactivation of microglia leads to neuronal death that is associated with CNS disorders. Therefore, regulation of microglial activation has been suggested to be an important target for treatment of CNS diseases. In the present study, we investigated the beneficial effect of resveratrol, a natural phenol with antioxidant effects, in the microglial cell line, BV2, in a model of hypoxia injury. Resveratrol suppressed the mRNA expression of the pro-inflammatory molecule, tumor necrosis factor-α, and promoted the mRNA expression of the anti-inflammatory molecule, interleukin-10, in BV2 microglia under hypoxic conditions. In addition, resveratrol inhibited the activation of the transcription factor, nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), which is upstream in the control of inflammatory reactions in hypoxia-injured BV2 microglia. Moreover, resveratrol promoted the expression of brain-derived neurotrophic factor (BDNF) in BV2 microglia under hypoxic stress. Overall, resveratrol may promote the beneficial function of microglia in ischemic brain injury. Full article
(This article belongs to the Special Issue Pharmaceuticals and Nutraceuticals by Molecular Farming)
Open AccessArticle Enhancement of Chlorogenic Acid Production in Hairy Roots of Platycodon grandiflorum by Over-Expression of An Arabidopsis thaliana Transcription Factor AtPAP1
Int. J. Mol. Sci. 2014, 15(8), 14743-14752; doi:10.3390/ijms150814743
Received: 30 May 2014 / Revised: 17 July 2014 / Accepted: 22 July 2014 / Published: 22 August 2014
Cited by 1 | PDF Full-text (860 KB) | HTML Full-text | XML Full-text
Abstract
To improve the production of chlorogenic acid (CGA) in hairy roots of Platycodon grandiflorum, we induced over-expression of Arabidopsis thaliana transcription factor production of anthocyanin pigment (AtPAP1) using an Agrobacterium rhizogenes-mediated transformation system. Twelve hairy root lines showing over-expression of [...] Read more.
To improve the production of chlorogenic acid (CGA) in hairy roots of Platycodon grandiflorum, we induced over-expression of Arabidopsis thaliana transcription factor production of anthocyanin pigment (AtPAP1) using an Agrobacterium rhizogenes-mediated transformation system. Twelve hairy root lines showing over-expression of AtPAP1 were generated. In order to investigate the regulation of AtPAP1 on the activities of CGA biosynthetic genes, the expression levels of seven P. grandiflorum CGA biosynthetic genes were analyzed in the hairy root line that had the greatest accumulation of AtPAP1 transcript, OxPAP1-1. The introduction of AtPAP1 increased the mRNA levels of all examined CGA biosynthetic genes and resulted in a 900% up-regulation of CGA accumulation in OxPAP1-1 hairy roots relative to controls. This suggests that P. grandiflorum hairy roots that over-express the AtPAP1 gene are a potential alternative source of roots for the production of CGA. Full article
(This article belongs to the Special Issue Pharmaceuticals and Nutraceuticals by Molecular Farming)

Review

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Open AccessReview Nutritionally Enhanced Food Crops; Progress and Perspectives
Int. J. Mol. Sci. 2015, 16(2), 3895-3914; doi:10.3390/ijms16023895
Received: 22 December 2014 / Accepted: 4 February 2015 / Published: 11 February 2015
Cited by 11 | PDF Full-text (699 KB) | HTML Full-text | XML Full-text
Abstract
Great progress has been made over the past decade with respect to the application of biotechnology to generate nutritionally improved food crops. Biofortified staple crops such as rice, maize and wheat harboring essential micronutrients to benefit the world’s poor are under development [...] Read more.
Great progress has been made over the past decade with respect to the application of biotechnology to generate nutritionally improved food crops. Biofortified staple crops such as rice, maize and wheat harboring essential micronutrients to benefit the world’s poor are under development as well as new varieties of crops which have the ability to combat chronic disease. This review discusses the improvement of the nutritional status of crops to make a positive impact on global human health. Several examples of nutritionally enhanced crops which have been developed using biotechnological approaches will be discussed. These range from biofortified crops to crops with novel abilities to fight disease. The review concludes with a discussion of hurdles faced with respect to public perception, as well as directions of future research and development for nutritionally enhanced food crops. Full article
(This article belongs to the Special Issue Pharmaceuticals and Nutraceuticals by Molecular Farming)

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