Northeast Ohio Medical University, also known as NEOMED, and formerly known as the Northeastern Ohio Universities Colleges of Medicine and Pharmacy , is a community-based, public state university that offers M.D., B.S./M.D., Pharm.D., M.P.H., M.S., and Ph.D. degrees. Wikipedia.
Chiang J.Y.L.,Northeast Ohio Medical University
Comprehensive Physiology | Year: 2013
Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. © 2013 American Physiological Society.
Li T.,University of Kansas Medical Center |
Chiang J.Y.L.,Northeast Ohio Medical University
Current Opinion in Gastroenterology | Year: 2015
PURPOSE OF REVIEW: This review focuses on the latest understanding of the molecular mechanisms underlying the complex interactions between intestine and liver bile acid signaling, gut microbiota, and their impact on whole-body lipid, glucose and energy metabolism. RECENT FINDINGS: Hepatic bile acid synthesis is tightly regulated by the bile acid negative feedback mechanisms. Modulating the enterohepatic bile acid signaling greatly impacts the whole-body metabolic homeostasis. Recently, a positive feedback mechanism through intestine farnesoid X receptor (FXR) antagonism has been proposed to link gut microbiota to the regulation of bile acid composition and pool size. Two studies identified intestine Diet1 and hepatic SHP-2 as novel regulators of CYP7A1 and bile acid synthesis through the gut-liver FXR-fibroblast growth factor 15/19-FGF receptor four signaling axis. New evidence suggests that enhancing bile acid signaling in the distal ileum and colon contributes to the metabolic benefits of bile acid sequestrants and bariatric surgery. SUMMARY: Small-molecule ligands that target TGR5 and FXR have shown promise in treating various metabolic and inflammation-related human diseases. New insights into the mechanisms underlying the bariatric surgery and bile acid sequestrant treatment suggest that targeting the enterohepatic circulation to modulate gut-liver bile acid signaling, incretin production and microbiota represents a new strategy to treat obesity and type 2 diabetes. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Li T.,University of Kansas Medical Center |
Chiang J.Y.L.,Northeast Ohio Medical University
Pharmacological Reviews | Year: 2014
Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid-activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein-coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver. © 2014 by The American Society for Pharmacology and Experimental Therapeutics.
Lu Y.,Northeast Ohio Medical University
Neuroscience | Year: 2014
As the major excitatory neurotransmitter used in the vertebrate brain, glutamate activates ionotropic and metabotropic glutamate receptors (mGluRs), which mediate fast and slow neuronal actions, respectively. Important modulatory roles of mGluRs have been shown in many brain areas, and drugs targeting mGluRs have been developed for the treatment of brain disorders. Here, I review studies on mGluRs in the auditory system. Anatomical expression of mGluRs in the cochlear nucleus has been well characterized, while data for other auditory nuclei await more systematic investigations at both the light and electron microscopy levels. The physiology of mGluRs has been extensively studied using in vitro brain slice preparations, with a focus on the lower auditory brainstem in both mammals and birds. These in vitro physiological studies have revealed that mGluRs participate in neurotransmission, regulate ionic homeostasis, induce synaptic plasticity, and maintain the balance between excitation and inhibition in a variety of auditory structures. However, very few in vivo physiological studies on mGluRs in auditory processing have been undertaken at the systems level. Many questions regarding the essential roles of mGluRs in auditory processing still remain unanswered and more rigorous basic research is warranted. © 2014 IBRO.
Chen Y.-R.,Northeast Ohio Medical University |
Zweier J.L.,Northeast Ohio Medical University |
Zweier J.L.,Ohio State University
Circulation Research | Year: 2014
Mitochondrial reactive oxygen species (ROS) have emerged as an important mechanism of disease and redox signaling in the cardiovascular system. Under basal or pathological conditions, electron leakage for ROS production is primarily mediated by the electron transport chain and the proton motive force consisting of a membrane potential (ΔΨ) and a proton gradient (ΔpH). Several factors controlling ROS production in the mitochondria include flavin mononucleotide and flavin mononucleotide-binding domain of complex I, ubisemiquinone and quinone-binding domain of complex I, flavin adenine nucleotide-binding moiety and quinone-binding pocket of complex II, and unstable semiquinone mediated by the Q cycle of complex III. In mitochondrial complex I, specific cysteinyl redox domains modulate ROS production from the flavin mononucleotide moiety and iron-sulfur clusters. In the cardiovascular system, mitochondrial ROS have been linked to mediating the physiological effects of metabolic dilation and preconditioning-like mitochondrial ATP-sensitive potassium channel activation. Furthermore, oxidative post-translational modification by glutathione in complex I and complex II has been shown to affect enzymatic catalysis, protein-protein interactions, and enzyme-mediated ROS production. Conditions associated with oxidative or nitrosative stress, such as myocardial ischemia and reperfusion, increase mitochondrial ROS production via oxidative injury of complexes I and II and superoxide anion radical-induced hydroxyl radical production by aconitase. Further insight into cellular mechanisms by which specific redox post-translational modifications regulate ROS production in the mitochondria will enrich our understanding of redox signal transduction and identify new therapeutic targets for cardiovascular diseases in which oxidative stress perturbs normal redox signaling. © 2013 American Heart Association, Inc.
Barr R.G.,Northeast Ohio Medical University
Journal of Ultrasound in Medicine | Year: 2012
Breast elastography is a new sonographic technique that provides additional characterization information on breast lesions over conventional sonography and mammography. This technique provides information on the strain or hardness of a lesion, similar to a clinical palpation examination. Two techniques are now available for clinical use: strain (compression-based elastography) and shear wave elastography. Initial evaluation of these techniques in clinical trials suggests that they may substantially improve the characterization of breast lesions as benign or malignant. This improvement may substantially reduce the number of benign biopsies performed. Elastography can be performed by several methods and is now available from several manufactures. This article reviews the basics of this technique, how to perform the examination, image interpretation, and artifacts. Although easy to perform, technique is critical to obtain adequate images for interpretation. This primer will highlight the technique and point out common pitfalls. ©2012 by the American Institute of Ultrasound in Medicine.
Northeast Ohio Medical University | Date: 2013-03-14
The present invention relates to a methods for extending the period of filtering bleb survival and/or providing for long term bleb survival following Glaucoma Filtration Surgery by delivering an ALK-5 inhibitor to a wound area (the surgical site) of a patients eye. More particularly, the present invention relates to a method for the controlled delivery of an ALK-5 inhibitor to patients eye using a thermo-sensitive polymer formulation, wherein the ALK-5 inhibitor is first contained in the polymer formulation at a temperature sufficient to maintain the formulation as a liquid and then applied to the eye wound opening, wherein the formulation turns to a gel. The use of the thermo-sensitive gel with ALK-5 inhibitor contained therein, provides for longer term bleb survival following Glaucoma Filtration Surgery (GFS) on a patients eye. Thus, the present invention is particularly effective in inhibiting ocular fibrotic wound response following GFS.
Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 344.38K | Year: 2015
Bats are the only mammals capable of powered flight. Bats are also unusual among mammals because their wing bones bend during flight. Some bones bend to almost 90 degrees and do not fracture. However, little is known about how the materials that make up bat bones allow this unusual bending, or the genes that control the deposition and maintenance of this bone tissue. By studying the structure and genetic underpinnings of bat bones compared to terrestrial mammals, this work will show how bone cells work together to create this unusual bone. By building a bat-like bone matrix in a petri dish, it may be possible to get a bioprint of a synthetic material that can bend like bat bones without breaking. Workshops for pre-Kindergarten to high school students about how the bat got its wings have so far reached over 200 students in Northeastern Ohio and this outreach will be continued. Additionally, students around the world will benefit from a newly created educational website. Beyond these workshops, high school, undergraduate, and graduate students working as part of this project will receive interdisciplinary training in molecular, biomechanical, and nanostructural biological techniques.
By identifying the mechanisms required to create a resilient extracellular bone matrix in vivo and in vitro, this study is expected to expand our understanding of how bone performance is adjusted by constituent molecular processes and microstructure. We integrate RNA expression and mechanical performance in a flexible bone by undertaking structural and biomechanical analyses (nano-scale to whole bone), as well as in vivo and in vitro molecular assays of limb bone cells of volant and non-volant mammals. Specifically, this result could show how mammalian bone cells can synthesize a bat-like matrix in a 2D culture environment, and eventually allow the synthesis of a specialized 3D matrix in vivo. Overall this study will allow for multiple fields of research to understand and capitalize on what evolution selected as the key mechanisms needed to make an unusually flexible bone.
Agency: NSF | Branch: Continuing grant | Program: | Phase: Physiolg Mechansms&Biomechancs | Award Amount: 284.21K | Year: 2012
The juvenile stage of life can be particularly perilous. Immature animals must survive in the same environments as adults despite smaller body size, weaker muscles and other growth-related limitations on physical ability. Because, by definition, juveniles have yet to reproduce, one should expect strong selection for mechanisms that could potentially offset these age-related limits on physical performance, allowing individuals to reach adulthood, reproduce, and thus maintain evolutionary fitness. The proposed research will combine measures of musculoskeletal growth, physical performance, and survivorship in eastern cottontail rabbits (Sylvilagus floridanus) to explicitly test broad-scale hypotheses about the adaptive nature of mammalian growth and development. Eastern cottontails are independent of their mothers by three weeks of age and experience high predation pressure during the first year of life, making them an ideal species in which to address these issues. The fundamental data collected in this study will provide a greater understanding of how natural selection operates on musculoskeletal growth and development in response to predation, providing novel insight into the process of evolution itself.
This research is organized into three specific aims. First, researchers will collect detailed measures of musculoskeletal growth in eastern cottontails, including detailed data on muscle and bone strength. Second, the investigators will generate quantitative measures of physical performance ability (i.e., acceleration and sprinting capacities) in juvenile and adult rabbits. Finally, radio-tracking data will be combined with ecological data on home range size, habitat quality and predation risk to empirically document survivorship in juvenile rabbits. These data will allow the researchers to holistically examine associations among musculoskeletal anatomy, physical performance and evolutionary fitness, as required to formally test the adaptive significance of the traits thought to promote juvenile survival.
This project will create interdisciplinary collaborations among the three institutions involved, helping to foster a network of research and training in northeastern Ohio. Funding will also provide opportunities for undergraduates to learn in vivo biomechanical and field ecology methods. Such opportunities are rare and constitute a major educational resource for students. Skeletal materials gathered during this project will be donated to local museums and schools, providing valuable public educational and research tools. Finally, the survivorship estimates generated during this research can be used to inform the policy decisions of the Ohio Department of Natural Resources in order to establish acceptable numbers for hunting and trapping throughout Ohio.
Agency: NSF | Branch: Standard Grant | Program: | Phase: Biological Anthropology | Award Amount: 258.99K | Year: 2016
The majority of primate species are partially or completely tree-dwelling (arboreal), and they often captivate observers with their ability to walk and run with ease over narrow, steep, and bending branches. The goal of this project is to investigate the mechanics of quadrupedal locomotion (movement on four limbs) in wild primates moving in their natural environments, to provide a deeper understanding of primate arboreal athleticism. Past studies of primate quadrupedal mechanics have largely come from laboratory-based research, but in this study researchers will use advanced and durable video technologies that permit high-resolution measures of locomotion in the wild. The results of this project will further our understanding of locomotor adaptations that are thought to be central to the evolution of our early primate ancestors. The project will support undergraduate and graduate student training, and will enhance K-12 STEM education and public outreach through high school programs and collaborations with established science outreach programs at UT Austin. Findings from this project will be relevant to primate conservation efforts, science education, and community outreach at the field location.
This project will test hypotheses about the proximate and ultimate determinants of primate locomotor adaptation through analysis of ten free-ranging New World monkey species at the Tiputini Biodiversity Station in Ecuador. The investigators will document the locomotor kinematics of quadrupedal primates moving in their natural habitats using multi-camera, high-speed, high-resolution videography, sampling arboreal locomotion on a range of substrates and quantifying standard kinematic spatiotemporal variables. The morphology of the arboreal locomotor substrates will be quantified using novel methods, with specific measurements including substrate diameter, three-dimensional substrate orientation, substrate height above the ground, and substrate compliance. By analyzing the determinants of kinematic variation in an explicit phylogenetic framework, researchers will explore historical, allometric, and functional influences on primate quadrupedalism. This research will add to existing laboratory and field data, breaking new ground by lending ecological validity to standard metrics of gait performance and increasing the precision of standard field measurements of kinematics and substrate variation. The comparative phylogenetic framework will allow field testing of functional associations between kinematic features and aspects of substrate variation that have been previously demonstrated only in laboratory studies. Such knowledge is critical to understanding the adaptive context in which the distinctive aspects of primate quadrupedalism evolved.