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Articles 1 - 30 of 600

Full-Text Articles in Medical Physiology

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee Oct 2018

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR ...


Causality Analysis And Cell Network Modeling Of Spatial Calcium Signaling Patterns In Liver Lobules., Aalap Verma, Anil Noronha Antony, Babatunde A. Ogunnaike, Jan B. Hoek, Rajanikanth Vadigepalli Oct 2018

Causality Analysis And Cell Network Modeling Of Spatial Calcium Signaling Patterns In Liver Lobules., Aalap Verma, Anil Noronha Antony, Babatunde A. Ogunnaike, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Dynamics as well as localization of Ca2+ transients plays a vital role in liver function under homeostatic conditions, repair, and disease. In response to circulating hormonal stimuli, hepatocytes exhibit intracellular Ca2+ responses that propagate through liver lobules in a wave-like fashion. Although intracellular processes that control cell autonomous Ca2+ spiking behavior have been studied extensively, the intra- and inter-cellular signaling factors that regulate lobular scale spatial patterns and wave-like propagation of Ca2+ remain to be determined. To address this need, we acquired images of cytosolic Ca2+ transients in 1300 hepatocytes situated across several mouse liver lobules over a period of ...


High Fat Diet Upregulates Fatty Acid Oxidation And Ketogenesis Via Intervention Of Ppar-Γ., Kunal Sikder, Sanket Kumar Shukla, Neel Patel, Harpreet Singh, Khadija Rafiq Aug 2018

High Fat Diet Upregulates Fatty Acid Oxidation And Ketogenesis Via Intervention Of Ppar-Γ., Kunal Sikder, Sanket Kumar Shukla, Neel Patel, Harpreet Singh, Khadija Rafiq

Center for Translational Medicine Faculty Papers

BACKGROUND/AIMS: Systemic hyperlipidemia and intracellular lipid accumulation induced by chronic high fat diet (HFD) leads to enhanced fatty acid oxidation (FAO) and ketogenesis. The present study was aimed to determine whether activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) by surplus free fatty acids (FA) in hyperlipidemic condition, has a positive feedback regulation over FAO and ketogenic enzymes controlling lipotoxicity and cardiac apoptosis.

METHODS: 8 weeks old C57BL/6 wild type (WT) or PPAR-γ-/- mice were challenged with 16 weeks 60% HFD to induce obesity mediated type 2 diabetes mellitus (T2DM) and diabetic cardiomyopathy. Treatment course was followed by echocardiographic measurements ...


Changes In The Morphology Of Hypoglossal Motor Neurons In The Brainstem Of Developing Rats, Paul Allen Williams Jun 2018

Changes In The Morphology Of Hypoglossal Motor Neurons In The Brainstem Of Developing Rats, Paul Allen Williams

Loma Linda University Electronic Theses, Dissertations & Projects

The autonomic brainstem generates and modifies breathing rhythm by integrating inputs from chemo- and mechanosensors in the viscera while coordinating descending outputs from higher CNS structures. Hypoglossal motoneurons (XII MNs) receive inputs from respiratory premotor neurons in the medulla. Previous studies in rodents have demonstrated significant changes in breathing control during the first three weeks of life, with a sensitive period at 10 to 13 days post-birth (P10–P13) characterized by pronounced changes in neurotransmitters, receptors, excitation-inhibition balance, and breathing. However, age-dependent morphological changes of XII MNs during the first three weeks post-birth and especially during this sensitive period, have ...


Gene Delivery Of Adenoviral-Tmbim6 Vector Protects The Neonatal Brain After Hypoxic-Ischemic Injury, Desislava Doycheva Jun 2018

Gene Delivery Of Adenoviral-Tmbim6 Vector Protects The Neonatal Brain After Hypoxic-Ischemic Injury, Desislava Doycheva

Loma Linda University Electronic Theses, Dissertations & Projects

Neonatal hypoxia ischemia (HI) is an injury caused to the immature brain due to reduced cerebral blood flow which is associated with life-long neurological impairments. HI causes oxidative protein folding in the endoplasmic reticulum (ER), which results in ER stress. Generation of reactive oxygen species (ROS), from cytochrome P450 members (CYP) and NADPH-P450 reductases (NPR), in combination with activation of the unfolded protein response (UPR) are two major consequences of ER stress that cause oxidative damage and cell death. Herein we identified the role of Bax Inhibitor-1 (BI-1), an evolutionary conserved protein encoded by the Transmembrane Bax inhibitor Motif Containing ...


The Role Of Glucocorticoid Signaling In Prostate Cancer Health Disparities, Leanne W. Burnham Jun 2018

The Role Of Glucocorticoid Signaling In Prostate Cancer Health Disparities, Leanne W. Burnham

Loma Linda University Electronic Theses, Dissertations & Projects

African-American men are more likely to develop aggressive prostate cancer (PCa) and die from the disease than other ethnic groups. Glucocorticoid signaling is a contributing biological factor to worse PCa prognosis, and is emerging as a key driver of PCa progression in the absence of androgens. The mechanism involves glucocorticoids binding to glucocorticoid receptor (GR) and bypassing the androgen receptor (AR) signaling pathway to activate AR-target genes that promote tumor aggressiveness and therapy-resistance. This is problematic as African-American men have hypersensitive GR signaling and chronically-elevated levels of glucocorticoids linked to cumulative stressful life events. To explore the role of glucocorticoid ...


Systematic Pan-Cancer Analysis Of Somatic Allele Frequency., Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A Crandall, Nathan Edwards, Anelia Horvath May 2018

Systematic Pan-Cancer Analysis Of Somatic Allele Frequency., Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A Crandall, Nathan Edwards, Anelia Horvath

Pharmacology and Physiology Faculty Publications

Imbalanced expression of somatic alleles in cancer can suggest functional and selective features, and can therefore indicate possible driving potential of the underlying genetic variants. To explore the correlation between allele frequency of somatic variants and total gene expression of their harboring gene, we used the unique data set of matched tumor and normal RNA and DNA sequencing data of 5523 distinct single nucleotide variants in 381 individuals across 10 cancer types obtained from The Cancer Genome Atlas (TCGA). We analyzed the allele frequency in the context of the variant and gene functional features and linked it with changes in ...


Disruption Of Neonatal Cardiomyocyte Physiology Following Exposure To Bisphenol-A., Manelle Ramadan, Meredith Sherman, Rafael Jaimes, Ashika Chaluvadi, Luther Swift, Nikki Gillum Posnack May 2018

Disruption Of Neonatal Cardiomyocyte Physiology Following Exposure To Bisphenol-A., Manelle Ramadan, Meredith Sherman, Rafael Jaimes, Ashika Chaluvadi, Luther Swift, Nikki Gillum Posnack

Pharmacology and Physiology Faculty Publications

Bisphenol chemicals are commonly used in the manufacturing of polycarbonate plastics, polyvinyl chloride plastics, resins, and thermal printing applications. Humans are inadvertently exposed to bisphenols through contact with consumer products and/or medical devices. Recent reports have shown a link between bisphenol-a (BPA) exposure and adverse cardiovascular outcomes; although these studies have been limited to adult subjects and models. Since cardiac physiology differs significantly between the developing and adult heart, we aimed to assess the impact of BPA exposure on cardiac function, using a neonatal cardiomyocyte model. Neonatal rat ventricular myocytes were monitored to assess cell viability, spontaneous beating rate ...


Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin May 2018

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research ...


Tissue Engineered Micro And Macrovasculature Utilizing Stromal Vascular Fraction., Joseph Samir Zakhari May 2018

Tissue Engineered Micro And Macrovasculature Utilizing Stromal Vascular Fraction., Joseph Samir Zakhari

Electronic Theses and Dissertations

This dissertation describes the use of stromal vascular fraction to tissue engineer 3D microvasculature and macrovasculature. Stromal vascular fraction is an easily isolatable cell source from adipose tissue depots. It has demonstrated remarkable potential both in vitro and in vivo for forming microcirculation capable of perfusion upon implantation. SVF is clinically utilized as a therapeutic cell source for anti-inflammation for osteoarthritis and is being studied for ischemic tissue application to stimulate revascularization. The work described herein is divided within four chapters. Chapter I provides an introductory overview and lists the aims and hypothesis for the dissertation. Chapter II describes experiments ...


Multi-Scale Fluid Flow Analysis Of The Cardiovascular System, Zaid Mahmood Apr 2018

Multi-Scale Fluid Flow Analysis Of The Cardiovascular System, Zaid Mahmood

Dissertations and Theses

The hypoplastic left heart syndrome (HLHS) is one of the rarest congenital heart diseases affecting infants. Out of 150 babies born, one baby suffers from congenital heart disease. Furthermore, nine percent out of those suffering from congenital heart disease specifically suffer from hypoplastic left heart syndrome (HLHS). To this end, the Fontan operation which is a procedure to generate a harmonic blood flow in single functioning ventricle patients has been executed to palliate HLHS patients. In this operation, the inferior vena cava (IVC) and the superior vena cava (SVC), carrying the low-oxygenated blood returning from the lower and upper body ...


Melatonin Attenuates Oxidative Stress And Modulates Inflammatory Response After Experimental Burn Trauma, Minka Hristova, Ganka Bekyarova, Milena Atanasova, Maria Tzaneva Mar 2018

Melatonin Attenuates Oxidative Stress And Modulates Inflammatory Response After Experimental Burn Trauma, Minka Hristova, Ganka Bekyarova, Milena Atanasova, Maria Tzaneva

Journal of Mind and Medical Sciences

Introduction. Thermal injury activates an inflammatory response. Melatonin possesses anti-oxidant and anti-inflammatory properties. The objective of the present work was to study melatonin effects on the inflammatory response under conditions of oxidative stress during the early stage of thermal injury.

Materials and methods. We used 24 white male rats of Wistar breed, randomly divided into three experimental groups. Group one was the control, group two was inflicted with burn trauma, and group three was inflicted with burn trauma, with melatonin application following the thermal injury. Melatonin was applied twice in doses of 10 g/kg b.m. immediately after the ...


The Mind-Body Problem; Three Equations And One Solution Represented By Immaterial-Material Data, Ion G. Motofei, David L. Rowland Mar 2018

The Mind-Body Problem; Three Equations And One Solution Represented By Immaterial-Material Data, Ion G. Motofei, David L. Rowland

Journal of Mind and Medical Sciences

Human life occurs within a complex bio-psycho-social milieu, a heterogeneous system that is integrated by multiple bidirectional interrelations existing between the abstract-intangible ideas and physical-chemical support of environment. The mind is thus placed between the abstract ideas/ concepts and neurobiological brain that is further connected to environment. In other words, the mind acts as an interface between the immaterial (abstract/ intangible) data and material (biological) support. The science is unable to conceives and explains an interaction between the immaterial and material domains (to understand nature of the mind), this question generating in literature the mind-body problem. We have published in ...


Physiological And Cognitive Factors Related To Human Performance During The Grand Canyon Rim-To-Rim Hike, Kristin Divis, Clifford Anderson-Bergman, Robert Abbott, Victoria Newton, Glory Emmanuel-Aviña Jan 2018

Physiological And Cognitive Factors Related To Human Performance During The Grand Canyon Rim-To-Rim Hike, Kristin Divis, Clifford Anderson-Bergman, Robert Abbott, Victoria Newton, Glory Emmanuel-Aviña

Journal of Human Performance in Extreme Environments

Exposure to extreme environments is both mentally and physically taxing, leading to suboptimal performance and even life-threatening emergencies. Physiological and cognitive monitoring could provide the earliest indicator of performance decline and inform appropriate therapeutic intervention, yet little research has explored the relationship between these markers in strenuous settings. The Rim-to-Rim Wearables at the Canyon for Health (R2RWATCH) study is a research project at Sandia National Laboratories funded by the Defense Threat Reduction Agency to identify which physiological and cognitive phenomena collected by non-invasive wearable devices are the most related to performance in extreme environments. In a pilot study, data were ...


Optimization Of Wavelength Selection For Multispectral Image Acquisition: A Case Study Of Atrial Ablation Lesions, Huda Asfour, S. Guan, Narine Muselimyan, Luther M. Swift, Murray Loew, Narine Sarvazyan Jan 2018

Optimization Of Wavelength Selection For Multispectral Image Acquisition: A Case Study Of Atrial Ablation Lesions, Huda Asfour, S. Guan, Narine Muselimyan, Luther M. Swift, Murray Loew, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

In vivo autofluorescence hyperspectral imaging of moving objects can be challenging due to motion artifacts and to the limited amount of acquired photons. To address both limitations, we selectively reduced the number of spectral bands while maintaining accurate target identification. Several downsampling approaches were applied to data obtained from the atrial tissue of adult pigs with sites of radiofrequency ablation lesions. Standard image qualifiers such as the mean square error, the peak signal-to-noise ratio, the structural similarity index map, and an accuracy index of lesion component images were used to quantify the effects of spectral binning, an increased spectral distance ...


Rhythm: An Open Source Imaging Toolkit For Cardiac Panoramic Optical Mapping, Christopher Gloschat, Kedar Aras, Shubnam Gupta, N. Rokhana Faye, Hanyu Zhang, Matthew W. Kay, Igor R Efimov, +Several Additional Authors Jan 2018

Rhythm: An Open Source Imaging Toolkit For Cardiac Panoramic Optical Mapping, Christopher Gloschat, Kedar Aras, Shubnam Gupta, N. Rokhana Faye, Hanyu Zhang, Matthew W. Kay, Igor R Efimov, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Fluorescence optical imaging techniques have revolutionized the field of cardiac electrophysiology and advanced our understanding of complex electrical activities such as arrhythmias. However, traditional monocular optical mapping systems, despite having high spatial resolution, are restricted to a two-dimensional (2D) field of view. Consequently, tracking complex three-dimensional (3D) electrical waves such as during ventricular fibrillation is challenging as the waves rapidly move in and out of the field of view. This problem has been solved by panoramic imaging which uses multiple cameras to measure the electrical activity from the entire epicardial surface. However, the diverse engineering skill set and substantial resource ...


Sympatho-Excitatory Response To Pulmonary Chemosensitive Spinal Afferent Activation In Anesthetized, Vagotomized Rats, Julia A. Shanks, Zhiqiu Xia, Steven J. Lisco, George J. Rozanski, Harold D. Schultz, Irving H. Zucker, Han-Jun Wang Jan 2018

Sympatho-Excitatory Response To Pulmonary Chemosensitive Spinal Afferent Activation In Anesthetized, Vagotomized Rats, Julia A. Shanks, Zhiqiu Xia, Steven J. Lisco, George J. Rozanski, Harold D. Schultz, Irving H. Zucker, Han-Jun Wang

Journal Articles: Cellular & Integrative Physiology

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application ...


S-Nitrosation Of Protein Phosphatase 1 Mediates Alcohol-Induced Ciliary Dysfunction, Michael E. Price, Adam J. Case, Jacqueline A. Pavlik, Jane M. Devasure, Todd A. Wyatt, Matthew C. Zimmerman, Joseph H. Sisson Jan 2018

S-Nitrosation Of Protein Phosphatase 1 Mediates Alcohol-Induced Ciliary Dysfunction, Michael E. Price, Adam J. Case, Jacqueline A. Pavlik, Jane M. Devasure, Todd A. Wyatt, Matthew C. Zimmerman, Joseph H. Sisson

Journal Articles: Cellular & Integrative Physiology

Alcohol use disorder (AUD) is a strong risk factor for development and mortality of pneumonia. Mucociliary clearance, a key innate defense against pneumonia, is perturbed by alcohol use. Specifically, ciliated airway cells lose the ability to increase ciliary beat frequency (CBF) to β-agonist stimulation after prolonged alcohol exposure. We previously found that alcohol activates protein phosphatase 1 (PP1) through a redox mechanism to cause ciliary dysfunction. Therefore, we hypothesized that PP1 activity is enhanced by alcohol exposure through an S-nitrosothiol-dependent mechanism resulting in desensitization of CBF stimulation. Bronchoalveolar S-nitrosothiol (SNO) content and tracheal PP1 activity was increased in wild-type (WT ...


Influence Of Resistance Training On Vascular Function, Hemodynamic, And Perceived Exertion Responses To Fixed Submaximal Workloads In Patients With Coronary Disease, Kerstin Grafe Jan 2018

Influence Of Resistance Training On Vascular Function, Hemodynamic, And Perceived Exertion Responses To Fixed Submaximal Workloads In Patients With Coronary Disease, Kerstin Grafe

Master's Theses and Doctoral Dissertations

PURPOSE: To determine the impact of superimposed resistance training (RT) in aerobically trained coronary patients on systolic blood pressure (SBP), heart rate (HR), rating of perceived exertion (RPE; 6–20 scale), and rate pressure product (RPP) at fixed submaximal workloads following a 12-week RT intervention. Additionally, pre-and post-RT measures of brachial artery reactivity, an index of endothelial function, were obtained. METHODS: Fifteen low risk coronary patients (13 men, 2 women; mean ± SD age = 66.1 ± 5.1 yrs) completed a progressive 12-week RT program that complemented their regular aerobic training regimen. Prior to training, SBP, HR, RPP, and RPE were ...


Loss Of The Intellectual Disability And Autism Gene Cc2d1a And Its Homolog Cc2d1b Differentially Affect Spatial Memory, Anxiety, And Hyperactivity, Marta Zamarbide, Adam Oaks, Heather Pond, Julia Adelman, M. Chiara Manzini Jan 2018

Loss Of The Intellectual Disability And Autism Gene Cc2d1a And Its Homolog Cc2d1b Differentially Affect Spatial Memory, Anxiety, And Hyperactivity, Marta Zamarbide, Adam Oaks, Heather Pond, Julia Adelman, M. Chiara Manzini

Pharmacology and Physiology Faculty Publications

Hundreds of genes are mutated in non-syndromic intellectual disability (ID) and autism spectrum disorder (ASD), with each gene often involved in only a handful of cases. Such heterogeneity can be daunting, but rare recessive loss of function (LOF) mutations can be a good starting point to provide insight into the mechanisms of neurodevelopmental disease. Biallelic LOF mutations in the signaling scaffold CC2D1Acause a rare form of autosomal recessive ID, sometimes associated with ASD and seizures. In parallel, we recently reported that Cc2d1a-deficient mice present with cognitive and social deficits, hyperactivity and anxiety. In Drosophila, loss of the only ...


Translating Genetic And Preclinical Findings Into Autism Therapies, Maria Chahrour, Robin Kleiman, M Chiara Manzini Dec 2017

Translating Genetic And Preclinical Findings Into Autism Therapies, Maria Chahrour, Robin Kleiman, M Chiara Manzini

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic ...


Endothelin-1 And Hypoxic Vascular Remodeling In Ovine Fetal Cerebral Arteries, Jinjutha Silpanisong Dec 2017

Endothelin-1 And Hypoxic Vascular Remodeling In Ovine Fetal Cerebral Arteries, Jinjutha Silpanisong

Loma Linda University Electronic Theses, Dissertations & Projects

Intrauterine hypoxia resulting from decreased maternal oxygen uptake, insufficient oxygen carrying capacity, or compromised oxygen delivery to the fetus jeopardizes fetal oxygen delivery, detrimentally affecting growth and development of the immature vasculature. Hypoxia transiently increases Hypoxia Inducible Factor-1α (HIF- 1α), which complexes with HIF-1β to form the active HIF-1 dimer that can affect transcription. This temporary rise in HIF-1 can promote gene transcription of ligands such as Vascular Endothelial Growth Factor (VEGF) and Endothelin-1 (ET-1), which rises and falls with HIF levels. The absence of chronic elevation of these ligands prompted the question of how long-term effects of hypoxia is ...


Targeting Cancer Stem Cells In Recurrent Lung Cancer, Karen T. Udoh Nov 2017

Targeting Cancer Stem Cells In Recurrent Lung Cancer, Karen T. Udoh

Posters-at-the-Capitol

Lung cancer is the leading cause of cancer mortality in the world. Five-year survivability still remains dismal due to drug resistance. The development of drug resistance with cisplatin or platinum/taxane combination chemotherapies has led patients to suffer from recurrent lung cancer. These chemotherapy treatments target cancer cells but leave behind cancer stem cells. Cancer stem cells (CSCs) are stem-like tumor cells that have the potential to differentiate, self-renew, and proliferate. This allows the cancer to relapse even after initial elimination of the tumor. We hypothesize that Verrucarin J will inhibit cell proliferation in lung cancer cells and CSCs by ...


Finasteride As A Model For Personalized Medicine, Ion G. Motofei, David L. Rowland, Ioana Păunică, Octavian C. Tănăsescu, Petrişor Banu, Stana Păunică Oct 2017

Finasteride As A Model For Personalized Medicine, Ion G. Motofei, David L. Rowland, Ioana Păunică, Octavian C. Tănăsescu, Petrişor Banu, Stana Păunică

Journal of Mind and Medical Sciences

The side effects of Finasteride are currently a subject of controversy. Some studies report minor or acceptable adverse effects, which decrease after a variable period of time so that they do not necessitate terminating Finasteride administration. However, several clinical and neuro-endocrine studies show that some adverse effects persist indefinitely in the form of post-Finasteride syndrome, even after the drug cessation. This paper presents a possible explanation for these inconsistent findings. First, the study design of either informing or not informing patients prior therapy about possible adverse effects can influence the incidence and magnitude of reported adverse effects. Second, structural and ...


Direct Antioxidant Properties Of Methotrexate: Inhibition Of Malondialdehyde-Acetaldehyde-Protein Adduct Formation And Superoxide Scavenging., Matthew C. Zimmerman, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Carlos D. Hunter, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Daniel R. Anderson Oct 2017

Direct Antioxidant Properties Of Methotrexate: Inhibition Of Malondialdehyde-Acetaldehyde-Protein Adduct Formation And Superoxide Scavenging., Matthew C. Zimmerman, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Carlos D. Hunter, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Methotrexate (MTX) is an immunosuppressant commonly used for the treatment of autoimmune diseases. Recent observations have shown that patients treated with MTX also exhibit a reduced risk for the development of cardiovascular disease (CVD). Although MTX reduces systemic inflammation and tissue damage, the mechanisms by which MTX exerts these beneficial effects are not entirely known. We have previously demonstrated that protein adducts formed by the interaction of malondialdehyde (MDA) and acetaldehyde (AA), known as MAA-protein adducts, are present in diseased tissues of individuals with rheumatoid arthritis (RA) or CVD. In previously reported studies, MAA-adducts were shown to be highly immunogenic ...


Peptidyl-Prolyl Isomerase 1 Regulates Ca(2+) Handling By Modulating Sarco(Endo)Plasmic Reticulum Calcium Atpase And Na(2+)/Ca(2+) Exchanger 1 Protein Levels And Function, V Sacchi, B Wang, D Kubli, A Martinez, J Jin, R Alvarez, N Hariharan, C Glembotski, T Uchida, J Malter, Y Yang, P Gross, C Zhang, S Houser, Marcello Rota, M Sussman Oct 2017

Peptidyl-Prolyl Isomerase 1 Regulates Ca(2+) Handling By Modulating Sarco(Endo)Plasmic Reticulum Calcium Atpase And Na(2+)/Ca(2+) Exchanger 1 Protein Levels And Function, V Sacchi, B Wang, D Kubli, A Martinez, J Jin, R Alvarez, N Hariharan, C Glembotski, T Uchida, J Malter, Y Yang, P Gross, C Zhang, S Houser, Marcello Rota, M Sussman

NYMC Faculty Publications

BACKGROUND: Aberrant Ca(2+) handling is a prominent feature of heart failure. Elucidation of the molecular mechanisms responsible for aberrant Ca(2+) handling is essential for the development of strategies to blunt pathological changes in calcium dynamics. The peptidyl-prolyl cis-trans isomerase peptidyl-prolyl isomerase 1 (Pin1) is a critical mediator of myocardial hypertrophy development and cardiac progenitor cell cycle. However, the influence of Pin1 on calcium cycling regulation has not been explored. On the basis of these findings, the aim of this study is to define Pin1 as a novel modulator of Ca(2+) handling, with implications for improving myocardial contractility ...


Retinoic Acid Pathway Inhibition To Expand Human Hematopoietic Progenitor Cells With Islet Regenerative Capacity, Ruth Elgamal Sep 2017

Retinoic Acid Pathway Inhibition To Expand Human Hematopoietic Progenitor Cells With Islet Regenerative Capacity, Ruth Elgamal

Electronic Thesis and Dissertation Repository

Cellular therapy to induce islet regeneration is emerging as a novel treatment strategy for diabetes. Umbilical cord blood (UCB)-derived hematopoietic stem/progenitor cells (HSPC) isolated by high aldehyde dehydrogenase activity (ALDHhi) reduce hyperglycemia after transplantation into streptozotocin (STZ)-treated NOD/SCID mice. However, UCB-derived ALDHhi cells are rare and expansion without the loss of regenerative function is required. We hypothesized that BMS 493, an inverse retinoic acid receptor agonist, will prevent HSPC differentiation of HSPC during expansion, generating more ALDHhi cells for therapy. ALDHhi cells expanded for 6 days with BMS 493 showed a 2 ...


Temporal Changes In Cortical And Hippocampal Expression Of Genes Important For Brain Glucose Metabolism Following Controlled Cortical Impact Injury In Mice, June Zhou, Mark Burns, Linda Huynh, Sonia Villapol, Daniel D. Taub, Juan M. Saavedra, Marc R. Blackman Sep 2017

Temporal Changes In Cortical And Hippocampal Expression Of Genes Important For Brain Glucose Metabolism Following Controlled Cortical Impact Injury In Mice, June Zhou, Mark Burns, Linda Huynh, Sonia Villapol, Daniel D. Taub, Juan M. Saavedra, Marc R. Blackman

Pharmacology and Physiology Faculty Publications

Traumatic brain injury (TBI) causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group) underwent sham or unilateral controlled cortical impact (CCI) injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after ...


Overexpressed Somatic Alleles Are Enriched In Functional Elements In Breast Cancer., Paula Restrepo, Mercedeh Movassagh, Nawaf Alomran, Christian Miller, Muzi Li, Chris Trenkov, Yulian Manchev, Sonali Bahl, Stephanie Warnken, Liam Spurr, Tatiyana Apanasovich, Keith Crandall, Nathan Edwards, Anelia Horvath Aug 2017

Overexpressed Somatic Alleles Are Enriched In Functional Elements In Breast Cancer., Paula Restrepo, Mercedeh Movassagh, Nawaf Alomran, Christian Miller, Muzi Li, Chris Trenkov, Yulian Manchev, Sonali Bahl, Stephanie Warnken, Liam Spurr, Tatiyana Apanasovich, Keith Crandall, Nathan Edwards, Anelia Horvath

Pharmacology and Physiology Faculty Publications

Asymmetric allele content in the transcriptome can be indicative of functional and selective features of the underlying genetic variants. Yet, imbalanced alleles, especially from diploid genome regions, are poorly explored in cancer. Here we systematically quantify and integrate the variant allele fraction from corresponding RNA and DNA sequence data from patients with breast cancer acquired through The Cancer Genome Atlas (TCGA). We test for correlation between allele prevalence and functionality in known cancer-implicated genes from the Cancer Gene Census (CGC). We document significant allele-preferential expression of functional variants in CGC genes and across the entire dataset. Notably, we find frequent ...


Carotid Body-Mediated Chemoreflex Drive In The Setting Of Low And High Output Heart Failure., Rodrigo Del Rio, David C. Andrade, Camilo Toledo, Hugo S. Diaz, Claudia Lucero, Alexis Arce-Alvarez, Noah J. Marcus, Harold D. Schultz Aug 2017

Carotid Body-Mediated Chemoreflex Drive In The Setting Of Low And High Output Heart Failure., Rodrigo Del Rio, David C. Andrade, Camilo Toledo, Hugo S. Diaz, Claudia Lucero, Alexis Arce-Alvarez, Noah J. Marcus, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

Enhanced carotid body (CB) chemoreflex function is strongly related to cardiorespiratory disorders and disease progression in heart failure (HF). The mechanisms underlying CB sensitization during HF are not fully understood, however previous work indicates blood flow per se can affect CB function. Then, we hypothesized that the CB-mediated chemoreflex drive will be enhanced only in low output HF but not in high output HF. Myocardial infarcted rats and aorto-caval fistulated rats were used as a low output HF model (MI-CHF) and as a high output HF model (AV-CHF), respectively. Blood flow supply to the CB region was decreased only in ...