6 results on '"Loots, Gabriela G."'
Search Results
2. Synthetic antibacterial minerals: harnessing a natural geochemical reaction to combat antibiotic resistance
- Author
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Morrison, Keith D, Martin, Kelly A, Wimpenny, Josh B, and Loots, Gabriela G
- Subjects
Lung ,Prevention ,Vaccine Related ,Infectious Diseases ,Biodefense ,Antimicrobial Resistance ,Emerging Infectious Diseases ,Pneumonia ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Infection ,Animals ,Anti-Bacterial Agents ,Drug Resistance ,Bacterial ,Mice ,Microbial Sensitivity Tests ,Minerals ,NIH 3T3 Cells ,Silicates - Abstract
The overuse of antibiotics in clinical and livestock settings is accelerating the selection of multidrug resistant bacterial pathogens. Antibiotic resistant bacteria result in increased mortality and financial strain on the health care and livestock industry. The development of new antibiotics has stalled, and novel strategies are needed as we enter the age of antibiotic resistance. Certain naturally occurring clays have been shown to have antimicrobial properties and kill antibiotic resistant bacteria. Harnessing the activity of compounds within these clays that harbor antibiotic properties offers new therapeutic opportunities for fighting the potentially devastating effects of the post antibiotic era. However, natural samples are highly heterogenous and exhibit variable antibacterial effectiveness, therefore synthesizing minerals of high purity with reproducible antibacterial activity is needed. Here we describe for the first time synthetic smectite clay minerals and Fe-sulfide microspheres that reproduce the geochemical antibacterial properties observed in natural occurring clays. We show that these mineral formulations are effective at killing the ESKAPE pathogens (Enterococcus sp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter sp., Pseudomonas aeruginosa and Enterobacter sp.) by maintaining Fe2+ solubility and reactive oxygen species (ROS) production while buffering solution pH, unlike the application of metals alone. Our results represent the first step in utilizing a geochemical process to treat antibiotic resistant topical or gastrointestinal infections in the age of antibiotic resistance.
- Published
- 2022
3. Electric Fields at Breast Cancer and Cancer Cell Collective Galvanotaxis.
- Author
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Zhu, Kan, Hum, Nicholas R, Reid, Brian, Sun, Qin, Loots, Gabriela G, and Zhao, Min
- Abstract
Cancer growth interferes with local ionic environments, membrane potentials, and transepithelial potentials, resulting in small electrical changes in the tumor microenvironment. Electrical fields (EFs) have significant effects on cancer cell migration (galvanotaxis/electrotaxis), however, their role as a regulator of cancer progression and metastasis is poorly understood. Here, we employed unique probe systems to characterize the electrical properties of cancer cells and their migratory ability under an EF. Subcutaneous tumors were established from a triple-negative murine breast cancer cell line (4T1), electric currents and potentials of tumors were measured using vibrating probe and glass microelectrodes, respectively. Steady outward and inward currents could be detected at different positions on the tumor surface and magnitudes of the electric currents on the tumor surface strongly correlated with tumor weights. Potential measurements also showed the non-homogeneous intratumor electric potentials. Cancer cell migration was then surveyed in the presence of EFs in vitro. Parental 4T1 cells and metastatic sublines in isolation showed random migration in EFs of physiological strength, whereas cells in monolayer migrated collectively to the anode. Our data contribute to an improved understanding of breast cancer metastasis, providing new evidence in support of an electrical mechanism that promotes this phenomenon.
- Published
- 2020
4. Manipulation of the Gut Microbiome Alters Acetaminophen Biodisposition in Mice
- Author
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Malfatti, Michael A, Kuhn, Edward A, Murugesh, Deepa K, Mendez, Melanie E, Hum, Nicholas, Thissen, James B, Jaing, Crystal J, and Loots, Gabriela G
- Subjects
Ecological Applications ,Biomedical and Clinical Sciences ,Biological Sciences ,Microbiology ,Environmental Sciences ,Vaccine Related ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Acetaminophen ,Administration ,Oral ,Amoxicillin ,Ampicillin ,Animals ,Anti-Bacterial Agents ,Drug Interactions ,Gastrointestinal Microbiome ,Male ,Metabolomics ,Mice ,Mice ,Inbred C57BL ,Neomycin ,Tissue Distribution ,Urine - Abstract
The gut microbiota is a vast and diverse microbial community that has co-evolved with its host to perform a variety of essential functions involved in the utilization of nutrients and the processing of xenobiotics. Shifts in the composition of gut microbiota can disturb the balance of organisms which can influence the biodisposition of orally administered drugs. To determine how changes in the gut microbiome can alter drug disposition, the pharmacokinetics (PK), and biodistribution of acetaminophen were assessed in C57Bl/6 mice after treatment with the antibiotics ciprofloxacin, amoxicillin, or a cocktail of ampicillin/neomycin. Altered PK, and excretion profiles of acetaminophen were observed in antibiotic exposed animals. Plasma Cmax was significantly decreased in antibiotic treated animals suggesting decreased bioavailability. Urinary metabolite profiles revealed decreases in acetaminophen-sulfate metabolite levels in both the amoxicillin and ampicillin/neomycin treated animals. The ratio between urinary and fecal excretion was also altered in antibiotic treated animals. Analysis of gut microbe composition revealed that changes in microbe content in antibiotic treated animals was associated with changes in acetaminophen biodisposition. These results suggest that exposure to amoxicillin or ampicillin/neomycin can alter the biodisposition of acetaminophen and that these alterations could be due to changes in gut microbiome composition.
- Published
- 2020
5. Functional and transcriptional characterization of complex neuronal co-cultures
- Author
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Enright, Heather A, Lam, Doris, Sebastian, Aimy, Sales, Ana Paula, Cadena, Jose, Hum, Nicholas R, Osburn, Joanne J, Peters, Sandra KG, Petkus, Bryan, Soscia, David A, Kulp, Kristen S, Loots, Gabriela G, Wheeler, Elizabeth K, and Fischer, Nicholas O
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Biomedical and Clinical Sciences ,Neurosciences ,Brain Disorders ,Biotechnology ,Neurodegenerative ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological ,Animals ,Astrocytes ,Cells ,Cultured ,Coculture Techniques ,Gene Expression Profiling ,Gene Regulatory Networks ,Lab-On-A-Chip Devices ,Neurogenesis ,Oligodendroglia ,Rats ,Sequence Analysis ,RNA ,Single-Cell Analysis ,Synaptophysin - Abstract
Brain-on-a-chip systems are designed to simulate brain activity using traditional in vitro cell culture on an engineered platform. It is a noninvasive tool to screen new drugs, evaluate toxicants, and elucidate disease mechanisms. However, successful recapitulation of brain function on these systems is dependent on the complexity of the cell culture. In this study, we increased cellular complexity of traditional (simple) neuronal cultures by co-culturing with astrocytes and oligodendrocyte precursor cells (complex culture). We evaluated and compared neuronal activity (e.g., network formation and maturation), cellular composition in long-term culture, and the transcriptome of the two cultures. Compared to simple cultures, neurons from complex co-cultures exhibited earlier synapse and network development and maturation, which was supported by localized synaptophysin expression, up-regulation of genes involved in mature neuronal processes, and synchronized neural network activity. Also, mature oligodendrocytes and reactive astrocytes were only detected in complex cultures upon transcriptomic analysis of age-matched cultures. Functionally, the GABA antagonist bicuculline had a greater influence on bursting activity in complex versus simple cultures. Collectively, the cellular complexity of brain-on-a-chip systems intrinsically develops cell type-specific phenotypes relevant to the brain while accelerating the maturation of neuronal networks, important features underdeveloped in traditional cultures.
- Published
- 2020
6. Tracking Tumor Colonization in Xenograft Mouse Models Using Accelerator Mass Spectrometry
- Author
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Hum, Nicholas R, Martin, Kelly A, Malfatti, Michael A, Haack, Kurt, Buchholz, Bruce A, and Loots, Gabriela G
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Biological Sciences ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Biotechnology ,Animals ,Carbon Isotopes ,Cell Tracking ,Disease Models ,Animal ,Humans ,Male ,Mass Spectrometry ,Mice ,Neoplasm Metastasis ,PC-3 Cells ,Prostatic Neoplasms ,Xenograft Model Antitumor Assays - Abstract
Here we introduce an Accelerator Mass Spectrometry (AMS)-based high precision method for quantifying the number of cancer cells that initiate metastatic tumors, in xenograft mice. Quantification of 14C per cell prior to injection into animals, and quantification of 14C in whole organs allows us to extrapolate the number of cancer cells available to initiate metastatic tumors. The 14C labeling was optimized such that 1 cancer cell was detected among 1 million normal cells. We show that ~1-5% of human cancer cells injected into immunodeficient mice form subcutaneous tumors, and even fewer cells initiate metastatic tumors. Comparisons of metastatic site colonization between a highly metastatic (PC3) and a non-metastatic (LnCap) cell line showed that PC3 cells colonize target tissues in greater quantities at 2 weeks post-delivery, and by 12 weeks post-delivery no 14C was detected in LnCap xenografts, suggesting that all metastatic cells were cleared. The 14C-signal correlated with the presence and the severity of metastatic tumors. AMS measurements of 14C-labeled cells provides a highly-sensitive, quantitative assay to experimentally evaluate metastasis and colonization of target tissues in xenograft mouse models. This approach can potentially be used to evaluate tumor aggressiveness and assist in making informed decisions regarding treatment.
- Published
- 2018
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