Medical Sciences Commons^™

Β-Aminopropionitrile-Induced Aortic Aneurysm And Dissection In Mice, Hisashi Sawada, Zachary A. Beckner, Sohei Ito, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

The mechanistic basis for the formation of aortic aneurysms and dissection needs to be elucidated to facilitate the development of effective medications. β-Aminopropionitrile administration in mice has been used frequently to study the pathologic features and mechanisms of aortic aneurysm and dissection. This mouse model mimics several facets of the pathology of human aortic aneurysms and dissection, although many variables exist in the experimental design and protocols that must be resolved to determine its application to the human disease. In the present brief review, we have introduced the development of this mouse model and provided insights into understanding its pathologic …

Single-Cell Analysis Of Aneurysmal Aortic Tissue In Patients With Marfan Syndrome Reveals Dysfunctional Tgf-Β Signaling, Ashley Dawson, Yanming Li, Yang Li, Pingping Ren, Hernan G. Vasquez, Chen Zhang, Kimberly R. Rebello, Waleed Ageedi, Alon R. Azares, Aladdein Burchett Mattar, Mary Burchett Sheppard, Hong S. Lu, Joseph S. Coselli, Lisa A. Cassis, Alan Daugherty, Ying H. Shen, Scott A. Lemaire

Saha Cardiovascular Research Center Faculty Publications

The molecular and cellular processes leading to aortic aneurysm development in Marfan syndrome (MFS) remain poorly understood. In this study, we examined the changes of aortic cell populations and gene expression in MFS by performing single-cell RNA sequencing (scRNA seq) on ascending aortic aneurysm tissues from patients with MFS (n = 3) and age-matched non-aneurysmal control tissues from cardiac donors and recipients (n = 4). The expression of key molecules was confirmed by immunostaining. We detected diverse populations of smooth muscle cells (SMCs), fibroblasts, and endothelial cells (ECs) in the aortic wall. Aortic tissues from MFS showed alterations …

Manganese-Enhanced Magnetic Resonance Imaging: Overview And Central Nervous System Applications With A Focus On Neurodegeneration, Ryan A. Cloyd, Shon A. Koren, Jose F. Abisambra

Physiology Faculty Publications

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Glimepiride Administered In Chow Reversibly Impairs Glucose Tolerance In Mice, Dana M. Niedowicz, Sabire Özcan, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Sulfonylureas are a class of antidiabetes medications prescribed to millions of individuals worldwide. Rodents have been used extensively to study sulfonylureas in the laboratory. Here, we report the results of studies treating mice with a sulfonylurea (glimepiride) in order to understand how the drug affects glucose homeostasis and tolerance. We tested the effect of glimepiride on fasting blood glucose, glucose tolerance, and insulin secretion, using glimepiride sourced from a local pharmacy. We also examined the effect on glucagon, gluconeogenesis, and insulin sensitivity. Unexpectedly, glimepiride exposure in mice was associated with fasting hyperglycemia, glucose intolerance, and decreased insulin. There was no …

Editorial: Ion Channel Trafficking And Cardiac Arrhythmias, Marcel A. G. Van Der Heyden, Brian P. Delisle, Hugues Abriel

Physiology Faculty Publications

No abstract provided.

Myocyte [Na+]I Dysregulation In Heart Failure And Diabetic Cardiomyopathy, Sanda Despa

Pharmacology and Nutritional Sciences Faculty Publications

By controlling the function of various sarcolemmal and mitochondrial ion transporters, intracellular Na⁺ concentration ([Na⁺]_i) regulates Ca²⁺ cycling, electrical activity, the matching of energy supply and demand, and oxidative stress in cardiac myocytes. Thus, maintenance of myocyte Na⁺ homeostasis is vital for preserving the electrical and contractile activity of the heart. [Na⁺]_i is set by the balance between the passive Na⁺ entry through numerous pathways and the pumping of Na⁺ out of the cell by the Na⁺/K⁺-ATPase. This equilibrium is perturbed in heart failure, …

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …

Artificial Gravity As A Countermeasure To The Cardiovascular Deconditioning Of Spaceflight: Gender Perspectives, Joyce M. Evans, Charles F. Knapp, Nandu Goswami

Biomedical Engineering Faculty Publications

Space flight-induced physiological deconditioning resulting from decreased gravitational input, decreased plasma volume, and disruption of regulatory mechanisms is a significant problem in returning astronauts as well as in normal aging. Here we review effects of a promising countermeasure on cardiovascular systems of healthy men and women undergoing Earth-based models of space-flight. This countermeasure is produced by a centrifuge and called artificial gravity (AG). Numerous studies have determined that AG improves orthostatic tolerance (as assessed by various protocols) of healthy ambulatory men, of men deconditioned by bed rest or by immersion (both wet and dry) and, in one case, following spaceflight. …

Alcohol Consumption Promotes Colorectal Carcinoma Metastasis Via A Ccl5-Induced And Ampk-Pathway-Mediated Activation Of Autophagy, Haodong Zhao, Danlei Chen, Rui Cao, Shiqing Wang, Dandan Yu, Yakun Liu, Yu Jiang, Mei Xu, Jia Luo, Siying Wang

Pharmacology and Nutritional Sciences Faculty Publications

There is a definite relationship between alcohol consumption and colorectal cancer (CRC) development. We investigated effect of alcohol consumption on CRC patients’ progression and prognosis by utilizing epidemiological data and found patients with alcohol consumption increased risks of tumor-node-metastasis (TNM), organ metastasis and poorer prognosis. Because their tumor tissues displayed increased expression of C-C chemokine ligand 5 (CCL5), we hypothesized CCL5 might participate in cancer progression in such patients. Ethanol increased the secretion of CCL5 in two CRC cell lines, HT29 and DLD-1. Treatment with CCL5 directly increased migratory ability of these cells, whereas neutralization or knockdown of CCL5 can …

Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi

Neurology Faculty Publications

Background: We report a patient who developed lower facial muscle spasm at rest and bilateral facial synkinesis several months after treatment of Guillain–Barré syndrome (GBS); this finding, to our knowledge, is hitherto unreported.

Phenomenology Shown: Bilateral synkinesis, facial muscles spasm at rest, bilateral postparalytic facial syndrome.

Educational Value: Aberrant regeneration of nerve fibers post GBS, resulting in facial muscles spasm at rest, bilateral synkinesis.

Comparison Of Serum And Cervical Cytokine Levels Throughout Pregnancy Between Preterm And Term Births, Kristin Ashford, Niraj R. Chavan, Amanda T. Wiggins, Molly Malany Sayre, Andrea Mccubbin, Agatha S. Critchfield, John O'Brien

Nursing Faculty Publications

Objective To assess differences in cytokine levels in cervicovaginal fluid (CVF) and serum across trimesters between women with preterm births (PTBs) and full-term births.

Study Design This multicenter study enrolled 302 women with a singleton gestation. CVF and serum cytokines, interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-8, were measured. Women with at least one cytokine assessment and noted PTB status in their medical record were retained in the study (N = 272). Data were analyzed using mixed modeling (main effects of PTBs and time/trimester).

Results For the CVF …

Amperometric Self-Referencing Ceramic Based Microelectrode Arrays For D-Serine Detection, Diana Campos-Beltrán, Åsa Konradsson-Geuken, Jorge E. Quintero, Lisa Marshall

Neuroscience Faculty Publications

D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO). We demonstrate in vitro D-serine recordings with a …

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …

Adropin: An Endocrine Link Between The Biological Clock And Cholesterol Homeostasis, Sarbani Ghoshal, Joseph R. Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S. Leon, D.C. Rao, James S. Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V. Nuñez, Kimber L. Stanhope, Deborah A. Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P. Weiss, Alisha R. Coffey, Brian J. Bennett, Praveen Sethupathy, Thomas P. Burris, Peter J. Havel, Andrew A. Butler

Physiology Faculty Publications

Objective

Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function.

Methods

Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models.

Results

In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = …

A Plasma Telomeric Cell-Free Dna Level In Unaffected Women With Brca1 Or/And Brca2 Mutations: A Pilot Study, Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N. Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He, Hiromi Tanaka

Internal Medicine Faculty Publications

Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls …

Epigenetic Impact Of Endocrine Disrupting Chemicals On Lipid Homeostasis And Atherosclerosis: A Pregnane X Receptor-Centric View, Robert N. Helsley, Changcheng Zhou

Pharmacology and Nutritional Sciences Faculty Publications

Despite the major advances in developing diagnostic techniques and effective treatments, atherosclerotic cardiovascular disease (CVD) is still the leading cause of mortality and morbidity worldwide. While considerable progress has been achieved to identify gene variations and environmental factors that contribute to CVD, much less is known about the role of “gene–environment interactions” in predisposing individuals to CVD. Our chemical environment has significantly changed in the last few decades, and there are more than 100,000 synthetic chemicals in the market. Recent large-scale human population studies have associated exposure to certain chemicals including many endocrine disrupting chemicals (EDCs) with increased CVD risk, …

Activin Receptor Type 2a (Acvr2a) Functions Directly In Osteoblasts As A Negative Regulator Of Bone Mass, Brian C. Goh, Vandana Singhal, Angelica J. Herrera, Ryan E. Tomlinson, Soohyun Kim, Marie-Claude Faugere, Emily L. Germain-Lee, Thomas L. Clemens, Se-Jin Lee, Douglas J. Digirolamo

Internal Medicine Faculty Publications

Bone and skeletal muscle mass are highly correlated in mammals, suggesting the existence of common anabolic signaling networks that coordinate the development of these two anatomically adjacent tissues. The activin signaling pathway is an attractive candidate to fulfill such a role. Here, we generated mice with conditional deletion of activin receptor (ACVR) type 2A, ACVR2B, or both, in osteoblasts, to determine the contribution of activin receptor signaling in regulating bone mass. Immunohistochemistry localized ACVR2A and ACVR2B to osteoblasts and osteocytes. Primary osteoblasts expressed activin signaling components, including ACVR2A, ACVR2B, and ACVR1B (ALK4) and demonstrated increased levels of phosphorylated Smad2/3 upon …

Hypersensitivity Of Vagal Pulmonary Afferents Induced By Tumor Necrosis Factor Alpha In Mice, Ruei-Lung Lin, Qihai Gu, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα), a pro-inflammatory cytokine, plays a significant role in the pathogenesis of allergic asthma. Inhalation of TNFα also induces airway hyperresponsiveness in healthy human subjects, and the underlying mechanism is not fully understood. A recent study reported that TNFα caused airway inflammation and a sustained elevation of pulmonary chemoreflex responses in mice, suggesting a possible involvement of heightened sensitivity of vagal pulmonary C-fibers. To investigate this possibility, the present study aimed to investigate the effect of a pretreatment with TNFα on the sensitivity of vagal pulmonary afferents in anesthetized mice. After TNFα (10 μg/ml, 0.03 ml) …

Tgf-Β Signaling: New Insights Into Aortic Aneurysms, Sean E. Thatcher

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.