31 research outputs found
The relationship between protein intake and source on factors associated with glycemic control in individuals with prediabetes and type 2 diabetes
Zinc and Traumatic Brain Injury: From Chelation to Supplementation
With a worldwide incidence rate of almost 70 million annually, traumatic brain injury (TBI) is a frequent cause of both disability and death. Our modern understanding of the zinc-regulated neurochemical, cellular, and molecular mechanisms associated with TBI is the result of a continuum of research spanning more than three decades. This review describes the evolution of the field beginning with the initial landmark work on the toxicity of excess neuronal zinc accumulation after injury. It further shows how the field has expanded and shifted to include examination of the cellular pools of zinc after TBI, identification of the role of zinc in TBI-regulated gene expression and neurogenesis, and the use of zinc to prevent cognitive and behavioral deficits associated with brain injury
Tracking stem cell migration and survival in brain injury: Current approaches and future prospects
In recent years, stem cell-mediated therapies have gained considerable ground as potential treatments for a wide variety of brain pathologies including traumatic brain injury, stroke and neurodegenerative diseases. Despite extensive preclinical studies, many of these therapies have not been fully translated into viable clinical approaches. This is partly due to our inability to reliably track and monitor transplanted stem cells longitudinally over long periods of time in vivo. In this review, we discuss the predominant histological cell tracing methodologies, such as immunohistochemistry, and fluorescent cellular dyes and proteins, and compare them to emerging cellular imaging technologies. We show that advances in magnetic resonance imaging (MRI) have resulted in opportunities to use this technology to further our understanding of stem cell characteristics and behaviors in vivo. While MRI may not completely replace conventional cell tracking methods in pre-clinical, mechanistic work, it is clear that it has the potential to function as a powerful diagnostic tool for tracking stem cell migration and survival as well as for evaluating the efficacy of stem cell-mediated therapies
Use of MRI, metabolomic, and genomic biomarkers to identify mechanisms of chemoresistance in glioma
Gliomas are the most common form of central nervous system tumor. The most prevalent form, glioblastoma multiforme, is also the most deadly with mean survival times that are less than 15 months. Therapies are severely limited by the ability of these tumors to develop resistance to both radiation and chemotherapy. Thus, new tools are needed to identify and monitor chemoresistance before and after the initiation of therapy and to maximize the initial treatment plan by identifying patterns of chemoresistance prior to the start of therapy. Here we show how magnetic resonance imaging, particularly sodium imaging, metabolomics, and genomics have all emerged as potential approaches toward the identification of biomarkers of chemoresistance. This work also illustrates how use of these tools together represents a particularly promising approach to understanding mechanisms of chemoresistance and the development individualized treatment strategies for patients
A Gold Nanoparticle Pentapeptide: Gene Fusion To Induce Therapeutic Gene Expression in Mesenchymal Stem Cells
Mesenchymal stem
cells (MSC) have been identified as having great
potential as autologous cell therapeutics to treat traumatic brain
injury and spinal injury as well as neuronal and cardiac ischemic
events. All future clinical applications of MSC cell therapies must
allow the MSC to be harvested, transfected, and induced to express
a desired protein or selection of proteins to have medical benefit.
For the full potential of MSC cell therapy to be realized, it is desirable
to systematically alter the protein expression of therapeutically
beneficial biomolecules in harvested MSC cells with high fidelity
in a single transfection event. We have developed a delivery platform
on the basis of the use of a solid gold nanoparticle that has been
surface modified to produce a fusion containing a zwitterionic, pentapeptide
designed from Bax inhibiting peptide (Ku70) to enhance cellular uptake
and a linearized expression vector to induce enhanced expression of
brain-derived neurotrophic factor (BDNF) in rat-derived MSCs. Ku70
is observed to effect >80% transfection following a single treatment
of femur bone marrow isolated rat MSCs with efficiencies for the delivery
of a 6.6 kbp gene on either a Au nanoparticle (NP) or CdSe/ZnS quantum
dot (QD). Gene expression is observed within 4 d by optical measurements,
and secretion is observed within 10 d by Western Blot analysis. The
combination of being able to selectively engineer the NP, to colocalize
biological agents, and to enhance the stability of those agents has
provided the strong impetus to utilize this novel class of materials
to engineer primary MSCs
Zinc deficiency regulates hippocampal gene expression and impairs neuronal differentiation
Improving Student Success in the Capstone Seminar: The Importance of a Prior Research Intensive Experience
Integrated and Passive 1,2,3-Triazolyl Groups in Fluorescent Indicators for Zinc(II) Ions: Thermodynamic and Kinetic Evaluations
In addition to being a covalent linker
in molecular conjugation
chemistry, the function of a 1,2,3-triazolyl moiety resulting from
the copper(I)-catalyzed azide–alkyne cycloaddition reaction
as a ligand for metal ions is receiving considerable attention. In
this work, we characterize the thermodynamic and kinetic effects of
incorporating a 1,2,3-triazolyl group in a multidentate ligand scaffold
on metal coordination in the context of fluorescent zinc(II) indicator
development. Ligands <b>L14</b>, <b>BrL14</b>, and <b>FL14</b> (1,4-isomers) contain the 1,4-disubstituted-1,2,3-triazolyl
group that is capable of binding with zinc(II) in conjunction with
a di(2-picolylamino) (DPA) moiety within a multidentate ligand scaffold.
Therefore, the 1,2,3-triazolyl in the 1,4-isomers is “integrated”
in chelation. The 1,5-isomers <b>L15</b>, <b>BrL15</b>, and <b>FL15</b> contain 1,2,3-triazolyls that are excluded
from participating in zinc(II) coordination. These 1,2,3-triazolyls
are “passive linkers”. Zinc(II) complexes of 2:1 (ligand/metal)
stoichiometry are identified in solution using <sup>1</sup>H NMR spectroscopy
and isothermal titration calorimetry (ITC) and, in one case, characterized
in the solid state. The 1:1 ligand/zinc(II) affinity ratio of <b>L14</b> over <b>L15</b>, which is attributed to the affinity
enhancement of a 1,2,3-triazolyl group to zinc(II) over that of the
solvent acetonitrile, is quantified at 18 (−1.7 kcal/mol at
298 K) using an ITC experiment. Fluorescent ligands <b>FL14</b> and <b>FL15</b> are evaluated for their potential in zinc(II)
sensing applications under pH neutral aqueous conditions. The 1,4-isomer <b>FL14</b> binds zinc(II) both stronger and faster than the 1,5-isomer <b>FL15</b>. Visualization of free zinc(II) ion distribution in live
HeLa cells is achieved using both <b>FL14</b> and <b>FL15</b>. The superiority of <b>FL14</b> in staining endogenous zinc(II)
ions in live rat hippocampal slices is evident. In summation, this
work is a fundamental study of 1,2,3-triazole coordination chemistry,
with a demonstration of its utility in developing fluorescent indicators