Publications by authors named "Justin X Zhong"

5 Publications

  • Page 1 of 1

Transthyretin amyloid fibrils alter primary fibroblast structure, function, and inflammatory gene expression.

Am J Physiol Heart Circ Physiol 2021 07 21;321(1):H149-H160. Epub 2021 May 21.

Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois.

Age-related wild-type transthyretin amyloidosis (wtATTR) is characterized by systemic deposition of amyloidogenic fibrils of misfolded transthyretin (TTR) in the connective tissue of many organs. In the heart, this leads to cardiac dysfunction, which is a significant cause of age-related heart failure. The hypothesis tested is that TTR affects cardiac fibroblasts in ways that may contribute to fibrosis. When primary cardiac fibroblasts were cultured on TTR-deposited substrates, the F-actin cytoskeleton was disorganized, focal adhesion formation was decreased, and nuclear shape was flattened. Fibroblasts had faster collective and single-cell migration velocities on TTR-deposited substrates. In addition, fibroblasts cultured on microposts with TTR deposition had reduced attachment and increased proliferation above untreated. Transcriptomic and proteomic analyses of fibroblasts grown on glass covered with TTR showed significant upregulation of inflammatory genes after 48 h, indicative of progression in TTR-based diseases. Together, results suggest that TTR deposited in tissue extracellular matrix may affect the structure, function, and gene expression of cardiac fibroblasts. As therapies for wtATTR are cost-prohibitive and only slow disease progression, better understanding of cellular maladaptation may elucidate novel therapeutic targets. Transthyretin (TTR) cardiac amyloidosis involves deposition of fibrils of misfolded TTR in the aging human heart, leading to cardiac dysfunction and heart failure. Our novel in vitro studies show that TTR fibrils alter primary cardiac fibroblast cytoskeletal and nuclear structure and focal adhesion formation. Furthermore, both fibrillar and tetrameric TTR significantly increased cellular migration velocity and caused upregulation of inflammatory genes determined by transcriptomic RNA and protein analysis. These findings may suggest new therapeutic approaches.
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http://dx.doi.org/10.1152/ajpheart.00073.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321815PMC
July 2021

Synthetic networks with tunable responsiveness, biodegradation, and molecular recognition for precision medicine applications.

Sci Adv 2019 09 27;5(9):eaax7946. Epub 2019 Sep 27.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.

Formulations and devices for precision medicine applications must be tunable and multiresponsive to treat heterogeneous patient populations in a calibrated and individual manner. We engineered modular poly(acrylamide-co-methacrylic acid) copolymers, cross-linked into multiresponsive nanogels with either a nondegradable or degradable disulfide cross-linker, that were customized via orthogonal chemistries to target biomarkers of an individual patient's disease or deliver multiple therapeutic modalities. Upon modification with functional small molecules, peptides, or proteins, these nanomaterials delivered methylene blue with environmental responsiveness, transduced visible light for photothermal therapy, acted as a functional enzyme, or promoted uptake by cells. In addition to quantifying the nanogels' composition, physicochemical characteristics, and cytotoxicity, we used a QCM-D method for characterizing nanomaterial degradation and a high-throughput assay for cellular uptake. In conclusion, we generated a tunable nanogel composition for precision medicine applications and new quantitative protocols for assessing the bioactivity of similar platforms.
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http://dx.doi.org/10.1126/sciadv.aax7946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764836PMC
September 2019

Tunable poly(methacrylic acid-co-acrylamide) nanoparticles through inverse emulsion polymerization.

J Biomed Mater Res A 2018 06 6;106(6):1677-1686. Epub 2018 Mar 6.

McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas.

Environmentally responsive biomaterials have played key roles in the design of biosensors and drug delivery vehicles. Their physical response to external stimuli, such as temperature or pH, can transduce a signal or trigger the release of a drug. In this work, we designed a robust, highly tunable, pH-responsive nanoscale hydrogel system. We present the design and characterization of poly(methacrylic acid-co-acrylamide) hydrogel nanoparticles, crosslinked with methylenebisacrylamide, through inverse emulsion polymerization. The effects of polymerization parameters (i.e., identities and concentrations of monomer and surfactant) and polymer composition (i.e., weight fraction of ionic and crosslinking monomers) on the nanoparticles' bulk and environmentally responsive properties were determined. We generated uniform, spherical nanoparticles which, through modulation of crosslinking, exhibit a volume swelling of 1.77-4.07, relative to the collapsed state in an acidic environment. We believe our system has potential as a base platform for the targeted, injectable delivery of hydrophilic therapeutics. With equal importance, however, we hope that our systematic analysis of the individual impacts of polymerization and purification conditions on nanoparticle composition, morphology, and performance can be used to expedite the development of alternate hydrophilic nanomaterials for a range of biomedical applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1677-1686, 2018.
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http://dx.doi.org/10.1002/jbm.a.36371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116730PMC
June 2018

Student award for outstanding research winner in the Ph.D. category for the 2017 society for biomaterials annual meeting and exposition, april 5-8, 2017, Minneapolis, Minnesota: Characterization of protein interactions with molecularly imprinted hydrogels that possess engineered affinity for high isoelectric point biomarkers.

J Biomed Mater Res A 2017 06 25;105(6):1565-1574. Epub 2017 Feb 25.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas.

Molecularly imprinted polymers (MIPs) with selective affinity for protein biomarkers could find extensive utility as environmentally robust, cost-efficient biomaterials for diagnostic and therapeutic applications. In order to develop recognitive, synthetic biomaterials for prohibitively expensive protein biomarkers, we have developed a molecular imprinting technique that utilizes structurally similar, analogue proteins. Hydrogel microparticles synthesized by molecular imprinting with trypsin, lysozyme, and cytochrome c possessed an increased affinity for alternate high isoelectric point biomarkers both in isolation and plasma-mimicking adsorption conditions. Imprinted and non-imprinted P(MAA-co-AAm-co-DEAEMA) microgels containing PMAO-PEGMA functionalized polycaprolactone nanoparticles were net-anionic, polydisperse, and irregularly shaped. MIPs and control non-imprinted polymers (NIPs) exhibited regions of Freundlich and BET isotherm adsorption behavior in a range of non-competitive protein solutions, where MIPs exhibited enhanced adsorption capacity in the Freundlich isotherm regions. In a competitive condition, imprinting with analogue templates (trypsin, lysozyme) increased the adsorption capacity of microgels for cytochrome c by 162% and 219%, respectively, as compared to a 122% increase provided by traditional bulk imprinting with cytochrome c. Our results suggest that molecular imprinting with analogue protein templates is a viable synthetic strategy for enhancing hydrogel-biomarker affinity and promoting specific protein adsorption behavior in biological fluids. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1565-1574, 2017.
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http://dx.doi.org/10.1002/jbm.a.36029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103214PMC
June 2017
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