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Full-Text Articles in Physiology

Potential Of Synthetic And Natural Compounds As Novel Histone Deacetylase Inhibitors For The Treatment Of Hematological Malignancies, Dilipkumar Pal, Khushboo Raj, Shyam Sundar Nandi, Surajit Sinha, Abhishek Mishra, Arijit Mondal, Ricardo Lagoa, Jack T. Burcher, Anupam Bishayee Jan 2023

Potential Of Synthetic And Natural Compounds As Novel Histone Deacetylase Inhibitors For The Treatment Of Hematological Malignancies, Dilipkumar Pal, Khushboo Raj, Shyam Sundar Nandi, Surajit Sinha, Abhishek Mishra, Arijit Mondal, Ricardo Lagoa, Jack T. Burcher, Anupam Bishayee

Journal Articles: Cellular & Integrative Physiology

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor …


The Effect Of Freeze-Thaw Events On Dna Integrity In The Gray Treefrog (Hyla Versicolor), Georgia Ficarra Jul 2021

The Effect Of Freeze-Thaw Events On Dna Integrity In The Gray Treefrog (Hyla Versicolor), Georgia Ficarra

Masters Theses & Specialist Projects

Freeze-tolerant gray treefrogs survive winter by producing natural cryoprotectants and accommodating ice formation within extracellular spaces. While frozen, gray treefrogs endure hyperglycemia, dehydration, and anoxia due to the halt of all bodily functions. Upon thawing, the frogs’ anoxic cells receive a rapid influx of oxygen, which can cause oxidative damage to vital macromolecules including DNA. Previous studies have suggested freeze-tolerant frogs avoid oxidative damage after freeze-thaw events by elevating antioxidant activity, but recent work has shown upregulated DNA repair encoding genes in post-freeze frogs. The objective of this thesis is to assess the cellular costs of freezing by measuring oxidative …


Association Of Oxidative Stress With Female Infertility - A Case Control Study, Faiza Alam, Taseer Ahmed Khan, Sofia Amjad, Rehana Rehman May 2019

Association Of Oxidative Stress With Female Infertility - A Case Control Study, Faiza Alam, Taseer Ahmed Khan, Sofia Amjad, Rehana Rehman

Department of Biological & Biomedical Sciences

Objective: To compare stress markers and reproductive hormones in fertile and infertile females, and to relate the markers with age, duration and cause of infertility, and body mass index..
Methods: The case-control study was conducted at Aga Khan University Hospital, Karachi, from March 2017 to February 2018. Females aged 16-50 years regardless of ethnic background were recruited from the Australian Concept Infertility Medical Centre, Karachi, and were equally divided into infertile cases group A, and fertile controls group B. Serum follicular stimulating hormone, luteinizing hormone, estradiol, glutathione reductase and cortisol were measured using enzyme-linked innmunosorbent assay. SPSS 19 …


Bovine Milk Extracellular Vesicles (Evs) Modification Elicits Skeletal Muscle Growth In Rats, Hailey A. Parry, Christopher Brooks Mobley, Petey W. Mumford, Matthew A. Romero, Cody T. Haun, Yufeng Zhang, Paul A. Roberson, Janos Zempleni, Arny A. Ferrando, Ivan J. Vechetti Jr., John J. Mccarthy, Kaelin C. Young, Michael D. Roberts, Andreas N. Kavazis Apr 2019

Bovine Milk Extracellular Vesicles (Evs) Modification Elicits Skeletal Muscle Growth In Rats, Hailey A. Parry, Christopher Brooks Mobley, Petey W. Mumford, Matthew A. Romero, Cody T. Haun, Yufeng Zhang, Paul A. Roberson, Janos Zempleni, Arny A. Ferrando, Ivan J. Vechetti Jr., John J. Mccarthy, Kaelin C. Young, Michael D. Roberts, Andreas N. Kavazis

Physiology Faculty Publications

The current study investigated how bovine milk extracellular vesicles (EVs) affected rotarod performance and biomarkers of skeletal muscle physiology in young, growing rats. Twenty-eight-day Fisher 344 rats were provided an AIN-93G-based diet for 4 weeks that either remained unadulterated [EVs and RNA-sufficient (ERS; n = 12)] or was sonicated [EVs and RNA-depleted (ERD; n = 12)]. Prior to (PRE) and on the last day of the intervention (POST), animals were tested for maximal rotarod performance. Following the feeding period, the gastrocnemius muscle was analyzed at the histological, biochemical, and molecular levels and was also used to measure mitochondrial function and …


Exercise Training Prevents The Perivascular Adipose Tissue-Induced Aortic Dysfunction With Metabolic Syndrome, Evan Devallance, Kayla W. Branyan, Kent C. Lemaster, Ray Anderson, Kent L. Marshall, I. Mark Olfert, David M. Smith, Eric E. Kelly, Randy W. Bryner, Jefferson C. Frisbee, Paul D. Chantler Jan 2019

Exercise Training Prevents The Perivascular Adipose Tissue-Induced Aortic Dysfunction With Metabolic Syndrome, Evan Devallance, Kayla W. Branyan, Kent C. Lemaster, Ray Anderson, Kent L. Marshall, I. Mark Olfert, David M. Smith, Eric E. Kelly, Randy W. Bryner, Jefferson C. Frisbee, Paul D. Chantler

Faculty & Staff Scholarship

The aim of the study was to determine the effects of exercise training on improving the thoracic perivascularadipose tissue (tPVAT) phenotype (inflammation, oxidative stress, and proteasome function) in metabolic syn-drome and its subsequent actions on aortic function.Methods:Lean and obese (model of metabolic syndrome) Zucker rats (n=8/group) underwent 8-weeks ofcontrol conditions or treadmill exercise (70% of max speed, 1 h/day, 5 days/week). At the end of the inter-vention, the tPVAT was removed and conditioned media was made. The cleaned aorta was attached to a forcetransducer to assess endothelium-dependent and independent dilation in the presence or absence of tPVAT-conditioned media. tPVAT gene …


Novel Antioxidant Properties Of Doxycycline, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Jacob D. Mcgowan, Carlos D. Hunter, Sarah L. Schlichte, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Matthew C. Zimmerman, Daniel R. Anderson Jan 2018

Novel Antioxidant Properties Of Doxycycline, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Jacob D. Mcgowan, Carlos D. Hunter, Sarah L. Schlichte, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Matthew C. Zimmerman, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen …


On The Origin Of Superoxide Dismutase: An Evolutionary Perspective Of Superoxide-Mediated Redox Signaling., Adam J. Case Jan 2017

On The Origin Of Superoxide Dismutase: An Evolutionary Perspective Of Superoxide-Mediated Redox Signaling., Adam J. Case

Journal Articles: Cellular & Integrative Physiology

The field of free radical biology originated with the discovery of superoxide dismutase (SOD) in 1969. Over the last 5 decades, a plethora of research has been performed in species ranging from bacteria to mammals that has elucidated the molecular reaction, subcellular location, and specific isoforms of SOD. However, while humans have only begun to study this class of enzymes over the past 50 years, it has been estimated that these enzymes have existed for billions of years, and may be some of the original enzymes found in primitive life. As life evolved over this expanse of time, these enzymes …


Increased Mitochondrial Superoxide In The Brain, But Not Periphery, Sensitizes Mice To Angiotensin Ii-Mediated Hypertension., Adam J. Case, Jun Tian, Matthew C. Zimmerman Nov 2016

Increased Mitochondrial Superoxide In The Brain, But Not Periphery, Sensitizes Mice To Angiotensin Ii-Mediated Hypertension., Adam J. Case, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Angiotensin II (AngII) elicits the production of superoxide (O2(•-)) from mitochondria in numerous cell types within peripheral organs and in the brain suggesting a role for mitochondrial-produced O2(•-) in the pathogenesis of hypertension. However, it remains unclear if mitochondrial O2(•-) is causal in the development of AngII-induced hypertension, or if mitochondrial O2(•-) in the absence of elevated AngII is sufficient to increase blood pressure. Further, the tissue specific (i.e. central versus peripheral) redox regulation of AngII hypertension remains elusive. Herein, we hypothesized that increased mitochondrial O2(•-) in the absence of pro-hypertensive stimuli, such as AngII, elevates baseline systemic mean arterial …


Effect Of Hydrogen Peroxide On The Biosynthesis Of Heme And Proteins: Potential Implications For The Partitioning Of Glu-TrnaGlu Between These Pathways, Carolina Farah, Gloria Levicán, Michael Ibba, Omar Orellana Dec 2014

Effect Of Hydrogen Peroxide On The Biosynthesis Of Heme And Proteins: Potential Implications For The Partitioning Of Glu-TrnaGlu Between These Pathways, Carolina Farah, Gloria Levicán, Michael Ibba, Omar Orellana

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Glutamyl-tRNA (Glu-tRNAGlu) is the common substrate for both protein translation and heme biosynthesis via the C5 pathway. Under normal conditions, an adequate supply of this aminoacyl-tRNA is available to both pathways. However, under certain circumstances, Glu-tRNAGlu can become scarce, resulting in competition between the two pathways for this aminoacyl-tRNA. In Acidithiobacillus ferrooxidans, glutamyl-tRNA synthetase 1 (GluRS1) is the main enzyme that synthesizes Glu-tRNAGlu. Previous studies have shown that GluRS1 is inactivated in vitro by hydrogen peroxide (H2O2). This raises the question as to whether H2O2 negatively affects …


Absence Of Manganese Superoxide Dismutase Delays P53-Induced Tumor Formation., Adam J. Case, Frederick E. Domann Jan 2014

Absence Of Manganese Superoxide Dismutase Delays P53-Induced Tumor Formation., Adam J. Case, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidant enzyme that is down-regulated in a majority of cancers. Due to this observation, as well as MnSOD's potent antioxidant enzymatic activity, MnSOD has been suggested as a tumor suppressor for over 30 years. However, testing this postulate has proven difficult due to the early post-natal lethality of the MnSOD constitutive knock-out mouse. We have previously used a conditional tissue-specific MnSOD knock-out mouse to study the effects of MnSOD loss on the development of various cell types, but long-term cancer development studies have not been performed. We hypothesized the complete loss of …


Voluntary Exercise Protects Against Methamphetamine-Induced Oxidative Stress In Brain Microvasculature And Disruption Of The Blood--Brain Barrier, Michal Toborek, Melissa J. Seelbach, Cetewayo S. Rashid, Ibolya E. András, Lei Chen, Minseon Park, Karyn A. Esser Jun 2013

Voluntary Exercise Protects Against Methamphetamine-Induced Oxidative Stress In Brain Microvasculature And Disruption Of The Blood--Brain Barrier, Michal Toborek, Melissa J. Seelbach, Cetewayo S. Rashid, Ibolya E. András, Lei Chen, Minseon Park, Karyn A. Esser

Physiology Faculty Publications

BACKGROUND: There is no effective therapeutic intervention developed targeting cerebrovascular toxicity of drugs of abuse, including methamphetamine (METH). We hypothesize that exercise protects against METH-induced disruption of the blood--brain barrier (BBB) by enhancing the antioxidant capacity of cerebral microvessels and modulating caveolae-associated signaling. Mice were subjected to voluntary wheel running for 5 weeks resembling the voluntary pattern of human exercise, followed by injection with METH (10 mg/kg). The frequency, duration, and intensity of each running session were monitored for each mouse via a direct data link to a computer and the running data are analyzed by Clock labTM Analysis software. …


The Effects Of Repeated Anaerobic Bouts On Immune Parameters, James C. Sivley Aug 2009

The Effects Of Repeated Anaerobic Bouts On Immune Parameters, James C. Sivley

Masters Theses & Specialist Projects

To date, the exercise-induced immune response in has only been evaluated in subjects performing aerobic exercise. The primary purpose of this study is to determine if repeated bouts of anaerobic exercise will induce a similar immune response in human subjects as exhibited by aerobic exercise. Secondary to immune function, an analysis of performance from trial to trial will be made. Nine males between the ages of 18-25 were selected on a volunteer basis to participate in this study. Subjects performed Wingate tests set in 3 series with 120 seconds between trials within series and 405 seconds between series for an …