A5031576950- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- FOXO transcription factor regulation
- Glycosylation and Glycoproteins Research
- Inflammatory mediators and NSAID effects
- Cancer Immunotherapy and Biomarkers
- Osteoarthritis Treatment and Mechanisms
- Virus-based gene therapy research
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Proteoglycans and glycosaminoglycans research
- Pain Mechanisms and Treatments
- Immune Cell Function and Interaction
- Protease and Inhibitor Mechanisms
- Adipose Tissue and Metabolism
- vaccines and immunoinformatics approaches
- Musculoskeletal pain and rehabilitation
- Cancer Cells and Metastasis
- Immune cells in cancer
- T-cell and B-cell Immunology
- Antimicrobial Peptides and Activities
- Cancer Genomics and Diagnostics
- Lipid metabolism and biosynthesis
- Mercury impact and mitigation studies
- Xenotransplantation and immune response
Jesse Brown VA Medical Center
2011-2025
University of Illinois Chicago
2015-2025
University of Illinois Urbana-Champaign
2005-2022
Illinois College
2005-2010
National Veterinary Research Institute
2007
The Wistar Institute
1998-2003
Creighton University
2000
University of Pennsylvania
1997-1999
FoxO proteins are major targets of insulin action. To better define the role FoxO1 in mediating effects liver, we generated liver-specific receptor knockout (LIRKO) and IR/FoxO1 double (LIRFKO) mice. Here show that LIRKO mice severely resistant based on glucose, C-peptide levels, glucose tolerance tests, genetic deletion hepatic reverses these effects. 13C-glucose clamp studies indicate regulation both production (HGP) utilization is impaired mice, defects also restored LIRFKO corresponding...
Drosocin, pyrrhocoricin, and apidaecin, representing the short (18−20 amino acid residues) proline-rich antibacterial peptide family, originally isolated from insects, were shown to act on a target bacterial protein in stereospecific manner. Native pyrrhocoricin one of its analogues designed for this purpose protect mice challenge and, therefore, may represent alternatives existing antimicrobial drugs. Furthermore, mode action can be basis design completely novel set compounds, peptidic or...
Osteoarthritis (OA) is characterized by cartilage damage, inflammation, and pain. Vascular endothelial growth factor receptors (VEGFRs) have been associated with OA severity, suggesting that inhibitors targeting these alleviate pain (via VEGFR1) or degeneration VEGFR2). We developed a nanoparticle-based formulation of pazopanib (Votrient), an FDA-approved anticancer drug targets both VEGFR1 VEGFR2 (Nano-PAZII). demonstrate single intraarticular injection Nano-PAZII can effectively reduce...
The focus of this investigation was to examine the effects low concentrations organic mercuric compounds on human monocyte function and relate these apoptosis. Following exposure monocytes 0–5 μM MeHgCl, phagocytic capacity generate a respiratory burst, following PMA activation, were determined. We found that mercury-treated cells exhibited reduced activity. Exposure same mercury concentration range, also caused marked increase in cell death. To ascertain if death due apoptosis, number flow...
Metabolism is a highly integrated process that coordinately regulated between tissues and within individual cells. FoxO proteins are major targets of insulin action contribute to the regulation gluconeogenesis, glycolysis, lipogenesis in liver. However, mechanisms by which exert these diverse effects an fashion remain poorly understood. We report also important on intrahepatic lipolysis fatty acid oxidation via adipose triacylglycerol lipase (ATGL), mediates first step lipolysis, its...
To test probiotic therapy for osteoarthritis (OA), we administered Lactobacillus acidophilus (LA) by oral gavage (2×/week) after induction of OA partial medial meniscectomy (PMM). Pain was assessed von Frey filament and hot plate testing. Joint pathology pain markers were comprehensively analyzed in knee joints, spinal cords, dorsal root ganglia distal colon Safranin O/fast green staining, immunofluorescence microscopy RT-qPCR. LA acutely reduced inflammatory joint prevented further...
The objective of our study was to define the mechanism by which MeHgCl induces human T-cell apoptosis. We asked question: does mercury disrupt Δψmand induce a mitochondrial permeability transition state? Using two fluorescent reagents, JC-1 and DiOC6(3), we demonstrated that exposure resulted in decrease Δψm.Since decline Δψmcan disturb pHi,we employed SNARF-1 assess pHi;results indicate treatment reduced pHifrom 7.0 6.5. Consistent with these observations, noted uncoupled electron transfer...
Pain is the major reason that patients suffering from osteoarthritis (OA) seek medical care.We found vascular endothelial growth factors (VEGFs) mediate signaling in OA pain pathways.To determine specific contributions of VEGFs and their receptors (VEGFRs) to joint pathology transmission during progression, we studied intra-articular (IA) injections VEGF ligands into murine knee joints.Only for activation VEGFR1, but not VEGFR2, induced allodynia within 30 min.Interventions by inhibitors...
<title>Abstract</title> Treatment by exogenous, bioactive, recombinant human N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) markedly reduced the number and volume of pulmonary melanomas in C57BL/6J mice inoculated intravenously with B16F10 melanoma cells. ARSB treatment induced apoptosis A375 cells increase expression E3 ubiquitin ligase constitutive photomorphogenic protein 1 (COP1), an inhibitor ultraviolet B-stimulated signaling <sup>5–12</sup>. The corresponding inhibitory...
Abstract The E3 ubiquitin ligase Constitutive Photomorphogenesis (COP)-1 inhibits UVB-induced light activation in plants by interaction with UV Receptor (UVR)8 and effects on hypocotyl elongation (HY)5-induced growth. UVB is recognized as a causative factor human melanomas, this the first identification of role COP1 inhibition melanoma growth correlation between UVB-stimulated melanomas. Following tail-vein injection 200, 000 B16F10 cells 14-week-old female C57BL/6J mice, intravenous...
Discogenic low back pain (DLBP) is extremely common and costly. Effective treatments are lacking due to DLBP's unknown pathogenesis. Currently, there no in vivo mouse models of DLBP, which restricts research this field. The aim study was establish a reliable DLBP model that captures the pathological changes disc allows longitudinal testing. generated by puncturing lumbar discs (L4/5, L5/6, L6/S1) removing nucleus pulposus using microscalpel under microscope. Histology, molecular pathways,...
Tropomyosin receptor kinase A (TrkA/NTRK1) is a high-affinity for nerve growth factor (NGF), potent pain mediator. NGF/TrkA signaling elevates synovial sensory neuronal distributions in the joints and causes osteoarthritis (OA) pain. We investigated mechanisms of transmission as to whether peripheral neurons are linked cellular plasticity dorsal root ganglia (DRG) critical OA hyperalgesia. Sensory neuron-specific deletion TrkA was achieved by tamoxifen injection 4-week-old...
Abstract Although degenerative disc disease (DDD) and related low back pain (LBP) are growing public health problems, the underlying mechanisms remain unclear. An increase in vascular endothelial growth factor (VEGF) levels DDD has been reported. This study aimed to examine role of VEGF receptors (VEGFRs) DDD, using a mouse model DDD. Progressive was induced by anterior stabbing lumbar intervertebral discs wild type (WT) VEGFR‐1 tyrosine‐kinase deficient mice ( vegfr‐1 TK−/ − ). Pain...
Liver-specific disruption of the type 2 deiodinase gene (Alb-D2KO) results in resistance to both diet-induced obesity and liver steatosis mice. Here, we report that this is explained by an ∼60% reduction zinc-finger protein-125 (Zfp125) expression. Zfp125 a Foxo1-inducible transcriptional repressor causes lipid accumulation AML12 mouse hepatic cell line mice reducing secretion triglycerides hepatocyte efflux cholesterol. acts repressing 18 genes involved lipoprotein structure, binding,...
Multiple beneficial cardiovascular effects of HDL depend on sphingosine-1-phosphate (S1P). S1P associates with by binding to apolipoprotein M (ApoM). Insulin resistance is a major driver dyslipidemia and risk. However, the mechanisms linking alterations in insulin signaling plasma lipoprotein metabolism are incompletely understood. The insulin-repressible FoxO transcription factors mediate key hepatic action glucose metabolism. This work tested whether regulates HDL-S1P aimed identify...