Research Terms
60.) Dowding, J., Seal, S. and W. T. Self (2013) Cerium oxide nanoparticles accelerate the decay of peroxynitrite (ONOO-). Drug Deliv Transl Res. Accepted, In press
59.) Boullait, L., Self, W. T. and A. L. Sonenshein (2013) Proline-Dependent Regulation of Clostridium difficile Stickland Metabolism. J. Bacteriol. 195(4):844.
58.) Das, S., Singh, S., Singh, V., Joung, D., Dowding, J.M., Zhai, L., Khondaker, S.I., Self, W. T. and Sudipta Seal (2013) Oxygenated functional group density on grapheme oxide: Its effect on cell toxicity. Particle and Particle Systems Characterization. Accepted, In press.
57.) Rosario, Sarah and W. T. Self (2013) Selenoenzymes and selenium trafficking: an emerging target for therapeutics. (book chapter) in Metals in Cells. Edited by Valeria Cullota and Robert A. Scott. John Wiley & Sons, Ltd, Chichester, United Kingdon. Accepted, In press
56.) W. T. Self (2013) Formate Dehydrogenase. Encyclopedia of Metalloproteins. V.N. Uversky, R.H. Kretsinger, E.A. Permyakov (eds.), Encyclopedia of Metalloproteins, Springer. DOI 10.1007/978-1-4614-1533-6 In press
55.) W. T. Self (2013) Purine Hydroxylase. Encyclopedia of Metalloproteins. V.N. Uversky, R.H. Kretsinger, E.A. Permyakov (eds.), Encyclopedia of Metalloproteins, Springer. DOI 10.1007/978-1-4614-1533-6 In press
54.) W. T. Self (2013) Xanthine Dehydrogenase. Encyclopedia of Metalloproteins. V.N. Uversky, R.H. Kretsinger, E.A. Permyakov (eds.), Encyclopedia of Metalloproteins, Springer. DOI 10.1007/978-1-4614-1533-6 In press
53.) W. T. Self (2013) Nicotinic Acid Hydroxylase. Encyclopedia of Metalloproteins. V.N. Uversky, R.H. Kretsinger, E.A. Permyakov (eds.), Encyclopedia of Metalloproteins, Springer. DOI 10.1007/978-1-4614-1533-6 In press
52.) Self, W. T. (2012) Selenium proteins containing selenocysteine. (book chapter) in Encyclopedia of Inorganic and Bioinorganic Chemistry. Robert A. Scott, Editor. John Wiley & Sons, Ltd, Chichester, United Kingdom. ISBN: 9781119951438 DOI: 10.1002/9781119951438.eibc0199.pub2
51.) Das, S., Singh, S., Dowding, J. M., Oommen, S., Kumar, A., Sayle, T.X.T., Saraf, S., Patra, C. R., Vlahakis, N. E., Sayle, D. C., Self, W. T. and S. Seal (2012) The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments. Biomaterials 33(31): 7746-7755.
50.) Dowding, J. M., Dosani, T., Kumar, A., Seal, S. and W. T. Self (2012) Cerium oxide nanoparticles scavenge nitric oxide radical (·NO). Chem. Comm. 48: 4896-4898.
49.) Singh, V., Das, S., Kumar, A., Singh, S., Self, W. T. and S. Seal (2012) A facile synthesis of PLGA encapsulated cerium oxide nano particles: Release kinetics and biological activity. Nanoscale. 4: 2597-2605.
48.) Srivastava, M., Singh, S. and W. T. Self (2011) Exposure to Silver Nanoparticles Inhibits Selenoprotein Synthesis and the Activity of Thioredoxin Reductase. Environ. Health Persp. 120:56-61.
47.) Singh, S., Dosani, T., Karakoti, A., Kumar, A., Seal, S. and W. T. Self (2011) A phosphate-dependent shift in redox state of cerium oxide nanoparticles and its effects on catalytic properties. Biomaterials 32:6745-6753.
46.) Srivastava, M., Mallard, C., Burke, T., Hancock, L. E. and W. T. Self (2011) A selenium-dependent xanthine dehydrogenase triggers biofilm proliferation in Enterococcus faecalis through oxidant production. J. Bacteriol. 193(7):1643-52.
45.) Cho J-H, Bass, M., Babu, S., Dowding, J. M., Self, W. T. and S. Seal (2011) Up conversion luminescence of Yb3+–Er3+ codoped CeO2 nanocrystals with imaging applications. J. Luminescence 132(3):743-749.
44.) Hirst, S. M., Karakoti, A., Singh, S., Self, W. T, Seal, S., and C. M. Reilly (2011) Bio-distribution and In Vivo Antioxidant Effects of Cerium Oxide Nanoparticles in Mice. Environ. Toxicol. DOI: 10.1002/tox.20704
43.) Karakoti, A., Singh, S., Dowding, J. M., Seal, S. and William T. Self* (2010) Redox-active Radical Scavenging Nanomaterials. Chem. Soc. Rev. 39, 4422–4432.
42.) Singh, S., Kumar, A., Karakoti, A., Seal, S. and W. T. Self (2010) Unveiling the mechanism of uptake and sub-cellular distribution of cerium oxide nanoparticles. Mol. Biosyst., 6, 1813-1820.
41.) Babu, S., Cho, J-H., Dowding, J., Heckert, E., Komanski, C., Soumen, D., Colon, J., Baker, C. H., Bass, M., Self, W. T. and S. Seal (2010) Multicolored redox active upconverter cerium oxide nanoparticle for bio-imaging and therapeutics. Chem. Comm., 46(37):6915-7.
40.) Pirmohamed, T., Dowding, J. M., Singh S., Wasserman, B., Heckert, E., Karakoti, A. S., King, J. E. S., Seal, S. and W. T. Self (2010) Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem. Comm., 46, 2736-2738.
39.) Vincent, A., Inerbaev, T., Babu, S., Karakoti, A., Self, W. T., Masunov, A., and Sudipta Seal (2010) Tuning Hydrated Nanoceria Surfaces: Experimental/Theoretical Investigations of Ion Exchange and Implications in Organic and Inorganic Interactions. Langmuir 26(10):7188-98.
38.) Wolfram M. Brück, W. M., Brück, T. B., Self, W. T., Reed, J. K., Nitecki, S. S. and Peter J. McCarthy (2010) Comparison of the anaerobic microbiota of deep water Geodia sp. and sandy sediments in the Florida straits The ISME Journal 4(5):686-99.
37.) Jackson-Rosario, S. and W. T. Self (2010) Targeting Selenium metabolism and selenoproteins: Novel avenues for drug discovery. Metallomics. 2:112-116.
36.) Self, W. T. (2010). “Selenium containing amino acids and selenoproteins”, In “Comprehensive Natural Products Chemistry II Chemistry and Biology (CONAP II), Mander, L., Lui, H.-W., Eds.; Elsevier: Oxford, 2010, Volume 5, pp. 121-148.
35.) Karakoti, A., Singh, S., Kumar, A., Malinska, M., Kuchibhatla, S., Wozniak, K., Self, W., and S. Seal (2009) PEGylated Nanoceria as Radical Scavenger with Tunable Redox Chemistry
J. Amer. Chem. Soc. 131 (40): 14144–14145.
34.) Schanen, B. C., Karakoti, A. S., Seal, S., Drake, D. R., Warren, W. L. and W. T. Self (2009) Exposure to Titanium Dioxide Nanomaterials Provokes Inflammation of an in Vitro Human Immune Construct. ACS Nano. 3 (9): 2523-2532.
33.) Jackson-Rosario, S. and W. T. Self (2009) Stannous salts inhibit selenium metabolism in the oral pathogen Treponema denticola. J. Bacteriol. 191(12): 4035-4040.
32.) Vincent, A., Babu, S, Heckert, E., Dowding, J., Hirst, S. M., Inerbaev, T. M., Self, W. T., Reilly, C. M., Masunov, A. M., and Sudipta Seal (2009) Protonated nanoparticle surface governing ligand tethering and cellular targeting. ACS Nano. 3 (5): 1203-1211.
31.) Jackson-Rosario, S., Cowart, D., Myers, A., Tarrien, R., Levine, R. L., Scott, R. and W. T. Self (2009). Auranofin disrupts selenium metabolism in Clostridium difficile by forming a stable Au-Se adduct: Identification and validation of a novel target for antimicrobial development. J. Biol. Inorg. Chem. May;14(4):507-19.
30.) Meno, S., Nelson, R., Hintze, K. J. and W. T. Self (2009). Exposure to monomethylarsonous acid (MMAIII) leads to altered selenoprotein synthesis in a primary human lung cell model. Toxicol. Appl. Pharm. 239(2):130-136.
29.) Seal, S., Self, W. T., McGinnis, J. and A.S. Karakoti. (2009) “Nanoparticles for Novel Healthcare Therapeutics” in New Materials and Technologies for Healthcare, Edited by Larry L. Hench and Julian R. Jones, Imperial College Press, London and Singapore
28.) Heckert, E., Seal, S. and W. T. Self (2008). Fenton-like reaction catalyzed by the rare earth inner transition metal cerium. Environ Sci Technol. (42) 5014-5019.
27.) Talbot, S. R., Nelson, R. and W. T. Self (2008). Arsenic trioxide (ATO) and auranofin inhibit selenoprotein synthesis: Implications for chemotherapy for acute promyelocytic leukemia (APL) Brit Journal of Pharmacology 154: 940-948.
26.) Heckert, E., Karakoti, A., Seal, S. and W. T. Self (2008). The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials. 29(18):2705-9.
25.) Ganyc, D. and W. T. Self (2008). High affinity selenium uptake in a keratinocyte model. FEBS Letters 582(2):299-304.
UCF researchers have invented a cerium oxide-based coating with anti-inflammatory/anti-oxidant properties that may delay or prevent osteolysis by reducing inflammation and the presence of free radicals while restoring the environment's electrochemical balance.
Although joint replacement surgeries have made remarkable progress, 10-15 percent of surgeries still fail due to high levels of free radicals, chronic inflammation from joint particles or debris generation through wear, and osteolysis (bone loss), or electrochemical dissolution/corrosion, requiring a growing number of revision surgeries. These types of operations are 40 percent more costly than primary total hip and knee arthroplasties, and more than $1 billion are spent on these procedures each year in the United States alone.
University of Central Florida researchers have developed new methods for using puupehenone compounds to possibly treat illnesses caused by Clostridium bacterial strains, such as C. difficile. Puupehenone is a marine natural product excreted by some species of sponges and coral as a defense mechanism. The UCF invention may also be effective against antibiotic-resistant strains of Clostridium.
Already resistant to multiple kinds of antibiotics, C. difficile kills 30,000-40,000 people a year in the United States. The pathogen inflames the colon, causing life-threatening diarrhea. Infections typically occur after antibiotic use and affect mostly elderly patients, those at long-term care facilities and hospitals and people with weakened immune systems.
The invention focuses on puupehenone's antimicrobial properties and methods for using concentrations of puupehenone-based compounds to kill, reduce or inhibit the cell growth of Clostridium bacterial strains, such as C. difficile, C. perfingens, C. tetani and C. botulinum. It includes methods for administering a therapeutically effective amount of a puupehenone compound (or a derivative) to those with a Clostridium infection or who are at risk of developing a Clostridium infection.
The invention developed by researchers at the University of Central Florida and the University of Toledo consists of new compound derivatives to treat Clostridioides difficile (C. difficile), Mycobacterium tuberculosis (M. tuberculosis) and Enterococcus faecalis (E. faecalis) infections. The derivatives are related to the known compounds (+)-Puupehenone and (+)-ent-Chromazonarol, both naturally occurring products. The new compound derivatives 1) inhibit both the growth and toxin production of C. difficile and 2) inhibit the growth and survival of both replicating and dormant M. tuberculosis in vitro.
Partnering Opportunity
The research team is seeking partners for licensing and/or research collaboration.
UCF scientists have discovered a method of doping nanoceria and other therapeutically valuable nanoparticles with rare earth metals for bioimaging and drug development applications. Nanoparticles are increasingly being used in the biological sciences for various therapeutic and research purposes. Nanoceria, for example, is a potentially powerful "nano-therapeutic." It has been shown to provide neurological protection, guard from radiation damage and it also exhibits Reactive Oxygen Species (ROS) scavenging properties. Little is known about where these nanoparticles locate within the human body. They are difficult to detect due to their small size and ability to traverse within affected cells. For these reasons, the need to track, locate and understand these nanoparticles within cells and biological systems are growing. It is possible to dope these nanoparticles with tags that will absorb UV light and emit in the visible spectrum, but there are several downsides to this. UV light has a high potential of damaging or even killing the very cells which are being studied. Additionally, these cells are prone to fluoresce themselves when exposed to UV light, distorting results.
Technical Details
After doping a therapeutic candidate using this technique, the compound will absorb infrared light and emit visible light through the process of up-conversion. This allows for easier identification, tracking and evaluation of the nanoparticle's functionality.
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