15 results on '"Kalita, Mausam"'
Search Results
2. Arabinofuranose‐derived positron‐emission tomography radiotracers for detection of pathogenic microorganisms.
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Kalita, Mausam, Parker, Matthew F.L., Luu, Justin M., Stewart, Megan N., Blecha, Joseph E., VanBrocklin, Henry F., Evans, Michael J., Flavell, Robert R., Rosenberg, Oren S., Ohliger, Michael A., and Wilson, David M.
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PATHOGENIC microorganisms , *RADIOACTIVE tracers , *DETECTION of microorganisms , *POSITRON emission tomography , *RADIOCHEMICAL purification - Abstract
PURPOSE: Detection of bacteria‐specific metabolism via positron emission tomography (PET) is an emerging strategy to image human pathogens, with dramatic implications for clinical practice. In silico and in vitro screening tools have recently been applied to this problem, with several monosaccharides including l‐arabinose showing rapid accumulation in Escherichia coli and other organisms. Our goal for this study was to evaluate several synthetically viable arabinofuranose‐derived 18F analogs for their incorporation into pathogenic bacteria. PROCEDURES: We synthesized four radiolabeled arabinofuranose‐derived sugars: 2‐deoxy‐2‐[18F]fluoro‐arabinofuranoses (d‐2‐18F‐AF and l‐2‐18F‐AF) and 5‐deoxy‐5‐[18F]fluoro‐arabinofuranoses (d‐5‐18F‐AF and l‐5‐18F‐AF). The arabinofuranoses were synthesized from 18F‐ via triflated, peracetylated precursors analogous to the most common radiosynthesis of 2‐deoxy‐2‐[18F]fluoro‐d‐glucose ([18F]FDG). These radiotracers were screened for their uptake into E. coli and Staphylococcus aureus. Subsequently, the sensitivity of d‐2‐18F‐AF and l‐2‐18F‐AF to key human pathogens was investigated in vitro. RESULTS: All 18F radiotracer targets were synthesized in high radiochemical purity. In the screening study, d‐2‐18F‐AF and l‐2‐18F‐AF showed greater accumulation in E. coli than in S. aureus. When evaluated in a panel of pathologic microorganisms, both d‐2‐18F‐AF and l‐2‐18F‐AF demonstrated sensitivity to most gram‐positive and gram‐negative bacteria. CONCLUSIONS: Arabinofuranose‐derived 18F PET radiotracers can be synthesized with high radiochemical purity. Our study showed absence of bacterial accumulation for 5‐substitued analogs, a finding that may have mechanistic implications for related tracers. Both d‐2‐18F‐AF and l‐2‐18F‐AF showed sensitivity to most gram‐negative and gram‐positive organisms. Future in vivo studies will evaluate the diagnostic accuracy of these radiotracers in animal models of infection. [ABSTRACT FROM AUTHOR]
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- 2020
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3. A Nanosensor for Ultrasensitive Detection of Oversulfated Chondroitin Sulfate Contaminant in Heparin.
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Kalita, Mausam, Balivada, Sivasai, Paritosh Swarup, Vimal, Mencio, Caitlin, Raman, Karthik, Desai, Umesh R., Troyer, Deryl, and Kuberan, Balagurunathan
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NANOSENSORS , *HEPARIN , *ANTICOAGULANTS , *CHONDROITIN , *CHONDROITIN sulfates - Abstract
Heparin has been extensively used as an anticoagulant for the last eight decades. Recently, the administration of a contaminated batch of heparin caused 149 deaths in several countries including USA, Germany, and Japan. The contaminant responsible for the adverse effects was identified as oversulfated chondroitin sulfate (OSCS). Here, we report a rapid, ultrasensitive method of detecting OSCS in heparin using a nanometal surface energy transfer (NSET) based gold-heparin-dye nanosensor. The sensor is an excellent substrate for heparitinase enzyme, as evidenced by ∼70% recovery of fluorescence from the dye upon heparitinase treatment. However, the presence of OSCS results in diminished fluorescence recovery from the nanosensor upon heparitinase treatment, as the enzyme is inhibited by the contaminant. The newly designed nanosensor can detect as low as 1 × 10-9 % (w/w) OSCS making it the most sensitive tool to date for the detection of trace amounts of OSCS in pharmaceutical heparins. [ABSTRACT FROM AUTHOR]
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- 2014
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4. Maleimide-Functionalized Photochromic Spirodihydroindolizines.
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Shrestha, Tej B., Kalita, Mausam, Pokhrel, Megh Raj, Yao Liu, Troyer, Deryl L., Turro, Claudia, Bossmann, Stefan H., and Dürr, Heinz
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BETAINE , *ALKALOIDS , *CONFORMERS (Chemistry) , *PEPTIDES , *MALEIMIDES - Abstract
Two photochromic spirodihydroindolizine/betaine systems for tethering to peptides and proteins via a maleimide function have been prepared. The absorption spectra of the betaines are in the red region of the visible spectrum and in the near-IR spectral domain, which are suitable energies of light for future in vivo applications. The half-times of cyclization have been determined for both DHI/betaine systems. The findings are consistent with a thermal barrier of varying size between the transoid and cisoid conformers of the betaines. [ABSTRACT FROM AUTHOR]
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- 2013
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5. Direct Synthesis of Aqueous Quantum Dots through 4,4'-Bipyridine-Based Twin Ligand Strategy.
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Kalita, Mausam, Cingarapu, Sreeram, Roy, Santanu, Park, Seok Chan, Higgins, Daniel, Jankowiak, Ryszard, Kiabunde, Kenneth J., and Bossmann, Stefan H.
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BIPYRIDINE , *QUANTUM dots , *BIPYRIDINIUM compounds , *LIGANDS (Chemistry) , *EVAPORATION (Chemistry) , *CONDENSATION - Abstract
We report a new class of derivatized 4,4'-bipyridinium ligands for use in synthesizing highly fluorescent, extremely stable, water-soluble CdSe and CdTe quantum dots (QDs) for bioconjugation. We employed an evaporation-condensation technique, also known as solvated metal atom dispersion (SMAD), followed by a digestive ripening procedure. This method has been used to synthesize both metal nanoparticles and semiconductors in the gram scale wish several stabilizing ligands in various solvents. The SMAD technique comprised evaporation condensation and stabilization of CdSe or CdTe in tetsahydrofuran. The as-prepared product was then digestively ripened in both water and dimethyl formamide, leading to narrowing of the particle size distributions. The ligands were synthesized by nucleophilic substitution (SN2) reactions using 4,4'-bipyridine as a nucleophile. Confocal microscopy images revealed the orange color of the nanocrystalline QDs with diameters of ΙS nm. The size has been confirmed by using transmission electron microscopy. As a part of our strategy, 85% of the 4,4'bipyridinium salt was synthesized as propionic arid derivative and used to both stabilize the QDs in water and label basic amino acids and different biomarkers utilizing the carboxylic acid functional group. Fifteen percent of the 4,4'-bipyridinium salt was synthesized as N-propyl maleimide and used as a second ligand to label any protein containing the amino acid cysteine by means of a 1,4-Michael addition. [ABSTRACT FROM AUTHOR]
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- 2012
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6. Iron-Based Magnetic Nanosystems for Diagnostic Imaging and Drug Delivery: Towards Transformative Biomedical Applications.
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Bossmann, Stefan H., Payne, Macy M., Kalita, Mausam, Bristow, Reece M. D., Afshar, Ayda, and Perera, Ayomi S.
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DIAGNOSTIC imaging , *IRON oxide nanoparticles , *IRON , *DRUGS - Abstract
The advancement of biomedicine in a socioeconomically sustainable manner while achieving efficient patient-care is imperative to the health and well-being of society. Magnetic systems consisting of iron based nanosized components have gained prominence among researchers in a multitude of biomedical applications. This review focuses on recent trends in the areas of diagnostic imaging and drug delivery that have benefited from iron-incorporated nanosystems, especially in cancer treatment, diagnosis and wound care applications. Discussion on imaging will emphasise on developments in MRI technology and hyperthermia based diagnosis, while advanced material synthesis and targeted, triggered transport will be the focus for drug delivery. Insights onto the challenges in transforming these technologies into day-to-day applications will also be explored with perceptions onto potential for patient-centred healthcare. [ABSTRACT FROM AUTHOR]
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- 2022
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7. A glycan-based approach to therapeutic angiogenesis.
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Chua, Jie Shi, Tran, Vy M., Kalita, Mausam, Quintero, Maritza V., Antelope, Orlando, Muruganandam, Geethu, Saijoh, Yukio, and Kuberan, Balagurunathan
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GLYCANS , *NEOVASCULARIZATION , *VASCULAR endothelial growth factors , *GLYCOSAMINOGLYCANS , *ENDOTHELIAL cells , *THERAPEUTICS - Abstract
Angiogenesis, the sprouting of new blood vessels from existing vasculature, involves multiple complex biological processes, and it is an essential step for hemostasis, tissue healing and regeneration. Angiogenesis stimulants can ameliorate human disease conditions including limb ischemia, chronic wounds, heart disease, and stroke. The current strategies to improve the bioavailability of pro-angiogenic growth factors, including VEGF and FGF2, have remained largely unsuccessful. This study demonstrates that small molecules, termed click-xylosides, can promote angiogenesis in the in vitro matrigel tube formation assay and the ex ovo chick chorioallantoic membrane assay, depending on their aglycone moieties. Xyloside treatment enhances network connectivity and cell survivability, thereby, maintaining the network structures on matrigel culture for an extended period of time. These effects were achieved via the secreted xyloside-primed glycosaminoglycans (GAG) chains that in part, act through an ERK1/2 mediated signaling pathway. Through the remodeling of GAGs in the extracellular matrix of endothelial cells, the glycan approach, involving xylosides, offers great potential to effectively promote therapeutic angiogenesis. [ABSTRACT FROM AUTHOR]
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- 2017
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8. Radiosynthesis and initial preclinical evaluation of [11C]AZD1283 as a potential P2Y12R PET radiotracer.
- Author
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Jackson, Isaac M., Buccino, Pablo J., Azevedo, E. Carmen, Carlson, Mackenzie L., Luo, Audrey S.Z., Deal, Emily M., Kalita, Mausam, Reyes, Samantha T., Shao, Xia, Beinat, Corinne, Nagy, Sydney C., Chaney, Aisling M., Anders, David A., Scott, Peter J.H., Smith, Mark, Shen, Bin, and James, Michelle L.
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HIGH performance liquid chromatography , *RADIOACTIVE tracers , *POSITRON emission tomography , *RHESUS monkeys , *KNOCKOUT mice , *LIVER analysis - Abstract
Chronic neuroinflammation and microglial dysfunction are key features of many neurological diseases, including Alzheimer's Disease and multiple sclerosis. While there is unfortunately a dearth of highly selective molecular imaging biomarkers/probes for studying microglia in vivo , P2Y12R has emerged as an attractive candidate PET biomarker being explored for this purpose. Importantly, P2Y12R is selectively expressed on microglia in the CNS and undergoes dynamic changes in expression according to inflammatory context (e.g. , toxic versus beneficial/healing states), thus having the potential to reveal functional information about microglia in living subjects. Herein, we identified a high affinity, small molecule P2Y12R antagonist (AZD1283) to radiolabel and assess as a candidate radiotracer through in vitro assays and in vivo positron emission tomography (PET) imaging of both wild-type and total knockout mice and a non-human primate. First, we evaluated the metabolic stability and passive permeability of non-radioactive AZD1283 in vitro. Next, we radiolabeled [11C]AZD1283 with radioactive precursor [11C]NH 4 CN and determined stability in formulation and human plasma. Finally, we investigated the in vivo stability and kinetics of [11C]AZD1283 via dynamic PET imaging of naïve wild-type mice, P2Y12R knockout mouse, and a rhesus macaque. We determined the half-life of AZD1283 in mouse and human liver microsomes to be 37 and > 160 min, respectively, and predicted passive CNS uptake with a small amount of active efflux, using a Caco-2 assay. Our radiolabeling efforts afforded [11C]AZD1283 in an activity of 12.69 ± 10.64 mCi with high chemical and radiochemical purity (>99%) and molar activity of 1142.84 ± 504.73 mCi/μmol (average of n = 3). Of note, we found [11C]AZD1283 to be highly stable in vitro , with >99% intact tracer present after 90 min of incubation in formulation and 60 min of incubation in human serum. PET imaging revealed negligible brain signal in healthy wild-type mice (n = 3) and a P2Y12 knockout mouse (0.55 ± 0.37%ID/g at 5 min post injection). Strikingly, high signal was detected in the liver of all mice within the first 20 min of administration (peak uptake = 58.28 ± 18.75%ID/g at 5 min post injection) and persisted for the remaining duration of the scan. Ex vivo gamma counting of mouse tissues at 60 min post-injection mirrored in vivo data with a mean %ID/g of 0.9% ± 0.40, 0.02% ± 0.01, and 106 ± 29.70% in the blood, brain, and liver, respectively (n = 4). High performance liquid chromatography (HPLC) analysis of murine blood and liver metabolite samples revealed a single radioactive peak (relative area under peak: 100%), representing intact tracer. Finally, PET imaging of a rhesus macaque also revealed negligible CNS uptake/binding in monkey brain (peak uptake = 0.37 Standard Uptake Values (SUV)). Despite our initial encouraging liver microsome and Caco-2 monolayer data, in addition to the observed high stability of [11C]AZD1283 in formulation and human serum, in vivo brain uptake was negligible and rapid accumulation was observed in the liver of both naïve wildtype and P2Y12R knockout mice. Liver signal appeared to be independent of both metabolism and P2Y12R expression due to the confirmation of intact tracer in this tissue for both wildtype and P2Y12R knockout mice. In Rhesus Macaque, negligible uptake of [11C]AZD1283 brain indicates a lack of potential for translation or its further investigation in vivo. P2Y12R is an extremely promising potential PET biomarker, and the data presented here suggests encouraging metabolic stability for this scaffold; however, the mechanism of liver uptake in mice should be elucidated prior to further analogue development. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2022
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9. A Hybrid Soft Solar Cell Based on the Mycobacterial Porin MspA Linked to a Sensitizer-Viologen Diad.
- Author
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Perera, Ayomi S., Subbaiyan, Navaneetha K., Kalita, Mausam, Wendel, Sebastian O., Samarakoon, Thilani N., D'Souza, Francis, and Bossmann, Stefan H.
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SOLAR cell design , *MYCOBACTERIAL diseases , *PORINS (Proteins) , *VIOLOGENS , *DYE-sensitized solar cells - Abstract
A prototype of a nano solar cell containing the mycobacterial channel protein MspA has been successfully designed. MspA, an octameric transmembrane channel protein from Mycobacterium smegmatis, is one of the most stable proteins known to date. Eight Ruthenium(II) aminophenanthroline-viologen maleimide Diads (Ru-Diads) have been successfully bound to the MspA mutant MspAA96C via cysteine-maleimide bonds. MspA is known to form double layers in which it acts as nanoscopic surfactant. The nanostructured layer that is formed by (Ru-Diad)8MspA at the TiO2 electrode is photochemically active. The resulting "protein nano solar cell" features an incident photon conversion efficiency of 1% at 400 nm. This can be regarded as a proof-of-principle that stable proteins can be successfully integrated into the design of solar cells. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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10. O-52 - Application of Machine Learning Driven Computational Approaches for Novel CNS PET Tracer Development.
- Author
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Jackson, Isaac, Luo, Audrey, Webb, Eric, Zhang, Bo, Guo, Allan, Nagy, Sydney, Shao, Xia, Kuo, Renesmee, Carlson, Mackenzie, Alam, Israt, Rodriguez, Angelie Rivera, Winton, Wade, Stauff, Jenelle, Kalita, Mausam, Scott, Peter, and James, Michelle Louise
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MACHINE learning - Published
- 2023
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11. Xyloside Primed Glycosaminoglycans Alter Hair Bundle Micromechanical Coupling and Synaptic Transmission: Pharmacokinetics.
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Holman, Holly A., Tran, Vy M., Nguyen, Lynn Y., Arungundram, Sailaja, Kalita, Mausam, Kuberan, Balagurunathan, and Rabbitt, Richard D.
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XYLOSIDE , *GLYCOSAMINOGLYCANS , *MICROELECTROMECHANICAL systems , *PHARMACOKINETICS , *CONFOCAL microscopy - Abstract
Glycosaminoglycans (GAGs) are ubiquitous in the inner ear, and disorders altering their structure or production often result in debilitating hearing and balance deficits. The specific mechanisms responsible for loss of haircell function are not well understood. We recently reported that introduction of a novel BODIPY conjugated xyloside (BX) into the endolymph primes fluorescent GAGs in vivo [6, 15]. Confocal and two-photon fluorescence imaging revealed rapid turnover and assembly of a glycocalyx enveloping the kinocilia and extending into the cupula, a structure that presumably serves as a mechanical link between the hair bundle and the cupula. Extracellular fluorescence was also observed around the basolateral surface of hair cells and surrounding afferent nerve projections into the crista. Single unit afferent recordings during mechanical hair bundle stimulation revealed temporary interruption of synaptic transmission following BX administration followed by recovery, demonstrating an essential role for GAGs in function of the hair cell synapse. In the present work we present a pharmacokinetic model to quantify the time course of BX primed GAG production and turnover in the ear. [ABSTRACT FROM AUTHOR]
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- 2016
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12. Xyloside Primed Glycosaminoglycans Alter Hair Bundle Micromechanical Coupling and Synaptic Transmission: Pharmacokinetics.
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Holman, Holly A., Tran, Vy M., Nguyen, Lynn Y., Arungundram, Sailaja, Kalita, Mausam, Kuberan, Balagurunathan, and Rabbitt, Richard D.
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GLYCOSAMINOGLYCANS , *XYLOSIDE , *HAIR cells , *MICROMECHANICS , *NEURAL transmission , *PHARMACOKINETICS - Abstract
Glycosaminoglycans (GAGs) are ubiquitous in the inner ear, and disorders altering their structure or production often result in debilitating hearing and balance deficits. The specific mechanisms responsible for loss of haircell function are not well understood. We recently reported that introduction of a novel BODIPY conjugated xyloside (BX) into the endolymph primes fluorescent GAGs in vivo [6, 15]. Confocal and two-photon fluorescence imaging revealed rapid turnover and assembly of a glycocalyx enveloping the kinocilia and extending into the cupula, a structure that presumably serves as a mechanical link between the hair bundle and the cupula. Extracellular fluorescence was also observed around the basolateral surface of hair cells and surrounding afferent nerve projections into the crista. Single unit afferent recordings during mechanical hair bundle stimulation revealed temporary interruption of synaptic transmission following BX administration followed by recovery, demonstrating an essential role for GAGs in function of the hair cell synapse. In the present work we present a pharmacokinetic model to quantify the time course of BX primed GAG production and turnover in the ear. [ABSTRACT FROM AUTHOR]
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- 2015
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13. Nanoplatforms for highly sensitive fluorescence detection of cancer-related proteases.
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Wang, Hongwang, Udukala, Dinusha N., Samarakoon, Thilani N., Basel, Matthew T., Kalita, Mausam, Abayaweera, Gayani, Manawadu, Harshi, Malalasekera, Aruni, Robinson, Colette, Villanueva, David, Maynez, Pamela, Bossmann, Leonie, Riedy, Elizabeth, Barriga, Jenny, Wang, Ni, Li, Ping, Higgins, Daniel A., Zhu, Gaohong, Troyer, Deryl L., and Bossmann, Stefan H.
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NANOMEDICAL research , *PROTEOLYTIC enzymes , *FLUORESCENCE , *FLUORESCENT dyes , *CANCER cells - Abstract
Numerous proteases are known to be necessary for cancer development and progression including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins. The goal of this research is to develop an Fe/Fe3O4 nanoparticle-based system for clinical diagnostics, which has the potential to measure the activity of cancer-associated proteases in biospecimens. Nanoparticle-based “light switches” for measuring protease activity consist of fluorescent cyanine dyes and porphyrins that are attached to Fe/Fe3O4 nanoparticles via consensus sequences. These consensus sequences can be cleaved in the presence of the correct protease, thus releasing a fluorescent dye from the Fe/Fe3O4 nanoparticle, resulting in highly sensitive (down to 1 × 10−16 mol l−1 for 12 proteases), selective, and fast nanoplatforms (required time: 60 min). [ABSTRACT FROM AUTHOR]
- Published
- 2014
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14. Channel Blocking of MspARevisited.
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Perera, Ayomi S., Wang, Hongwang, Basel, Matthew T., Pokhrel, Megh Raj, Gamage, Pubudu Siyambalagoda, Kalita, Mausam, Wendel, Sebastian, Sears, Bryan, Welideniya, Dhanushi, Liu, Yao, Turro, Claudia, Troyer, Deryl L., and Bossmann, Stefan H.
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MYCOBACTERIUM smegmatis , *ELECTROLYTES , *CELL membranes , *TUBERCULOSIS treatment , *RUTHENIUM compounds , *HIGH performance liquid chromatography - Abstract
Porin A from Mycobacterium smegmatis(MspA) is a highly stable, octameric channel protein, which actsas the main transporter of electrolytes across the cell membrane.MspA features a narrow, negatively charged constriction zone, allowingstable binding of various analytes thereby blocking the channel. Investigationof channel blocking of mycobacterial porins is of significance indeveloping alternate treatment methods for tuberculosis. The conceptthat ruthenium(II)quaterpyridinium complexes have the capability toact as efficient channel blockers for MspA and related porins, emergedafter very high binding constants were measured by high-performanceliquid chromatography and steady-state luminescence studies. Consequently,the interactions between the ruthenium(II) complex RuC2 moleculesand MspA, leading to RuC2@MspA assemblies, have been studied utilizingtime-resolved absorption/emission, atomic force microscopy, dynamiclight scattering, ζ potential measurements, and isothermal titrationcalorimetry. The results obtained provide evidence for the formationof clusters/large aggregates of RuC2 and MspA. The results are ofinterest with respect to utilizing prospective channel blockers inporins. The combination of results from conceptually different techniquesshed some light onto the chemical nature of MspA–channel blockerinteractions thus contributing to the development of a paradigm forchannel blocking. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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15. Stem cell-based photodynamic therapy.
- Author
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Shrestha, Tej B., Seo, Gwi M., Basel, Matthew T., Kalita, Mausam, Wang, Hongwang, Villanueva, David, Pyle, Marla, Balivada, Sivasai, Rachakatla, Raja Shekar, Shinogle, Heather, Thapa, Prem S., Moore, David, Troyer, Deryl L., and Bossmann, Stefan H.
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NEURAL stem cells , *LUCIFERASES , *PHOTODYNAMIC therapy , *LUNG cancer , *LABORATORY mice , *PROTOPORPHYRINS - Abstract
We have transfected murine neural stem cells (NSCs) and rat umbilical cord matrix-derived stem cells (RUCMSCs) with a plasmid expressing gaussia luciferase (gLuc). These cells are engineered to secrete the luciferase. We have used gLuc containing supernatant from culturing the NSCs to perform in vitro photodynamic therapy of murine melanoma cells (B16F10), and RUCMSCs to perform in vivo PDT of lung melanomas in C57BL/6 mice. The treatment system was comprised of aminolevulic acid as a prodrug for the synthesis of the photosensitizer protoporphyrin IX, gaussia luciferase, and its’ substrate coelenterazine. A significant reduction of the number of live melanoma cells in vitro and a borderline significant retardation of tumour growth in vivo was observed after coelenterazine-mediated PDT. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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