Medicine and Health Sciences Commons^™

Dna Methylation Signatures Of Chronic Low-Grade Inflammation Are Associated With Complex Diseases, Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler, Cavin K. Ward-Caviness, Brian H. Chen, Tianxiao Huan, Kelly Bakulski, Elias L. Salfati, Whi-Empc Investigators, Giovanni Fiorito, Charge Epigenetics Of Coronary Heart Disease, Simone Wahl, Katharina Schramm, Jin Sha, Dena G. Hernandez, Allan C. Just, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10^–7) in the discovery panel …

Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor

Electronic Theses & Dissertations

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Epidemiology And Impact Of Campylobacter Infection In Children In 8 Low-Resource Settings: Results From The Mal-Ed Study, Shahida Qureshi, Aneeta Hotwani, Sadia Shakoor, (Mal-Ed) Network Investigators, Imran Ahmed, Didar Alam, Syed Asad Ali, Zulfiqar Ahmed Bhutta, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Background: Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in low-resource settings. In a multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of Campylobacter infection in the first 2 years of life.
Methods: Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter Stool and blood samples were assayed for markers of intestinal permeability and inflammation.
Results: A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter We describe a high …

Glycemic Variability Predicts Inflammation In Adolescents With Type 1 Diabetes, Robert P. Hoffman, Amanda S. Dye, Hong Huang, John A. Bauer

Pediatrics Faculty Publications

Background: Adolescents with type 1 diabetes (T1D) have increased risk of cardiovascular disease as well as elevations in biomarkers of systemic inflammation, plasma protein oxidation and vascular endothelial injury. It is unclear whether hyperglycemia itself, or variations in blood glucose are predictors of these abnormalities.

Methods: This study was designed to determine the relationship of inflammatory (C-reactive protein, CRP), oxidative (total anti-oxidative capacity, TAOC) and endothelial injury (soluble intracellular adhesion molecule 1, sICAM1) markers to glycemic control measures from 3 days of continuous glucose monitoring (CGM) and to hemoglobin A_1c (HbA_1c), and HbA_1c×duration area under …

A Murine Model Of Inflammation-Induced Cerebral Microbleeds, Rachita K. Sumbria, Mher Mahoney Grigoryan, Vitaly Vasilevko, Tatiana B. Krasieva, Miriam Scadeng, Alexandra K. Dvornikova, Annlia Paganini-Hill, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to …

West Nile Virus And Pattern Recognition Receptors, Jordan Boswell, Verma Saguna, Phd, Chih-Yun Lai

Journal of Health Disparities Research and Practice

West Nile Virus (WNV), RNA virus is a member of the flaviviridae family that causes flu like symptoms in infected individuals, however in 1-2% cases, it causes severe neurological diseases such as encephalitis. There is no antiviral or vaccine approved so far to prevent WNV disease, therefore research to understand immune pathology is very important.

Pattern Recognition Receptors (PRR) are proteins that are expressed by cells to detect virus infection and play an important role in the innate immune system. When a PRR such as Toll-Like Receptors (TLR) and Nod-Like Receptors (NLR) detects a replicating virus, signals are sent out …

Hdac6 Inhibition Prevents Tnf-Α-Induced Caspase 3 Activation In Lung Endothelial Cell And Maintains Cell-Cell Junctions, Jinyan Yu, Mengshi Ma, Zhongsen Ma, Jian Fu

Center for Research on Environmental Disease Faculty Publications

Pro-inflammatory mediators such as TNF-α induce caspase activation in endothelial cells, which leads to degradation of cellular proteins, induction of apoptotic signaling, and endothelial cell dysfunction. New therapeutic agents that can inhibit caspase activation may provide protection against inflammatory injury to endothelial cells. In the present study, we examined the effects of selective histone deacetylase 6 (HDAC6) inhibition on TNF-α induced caspase 3 activation and cell-cell junction dysfunction in lung endothelial cells. We also assessed the protective effects of HDAC6 inhibition against lung inflammatory injury in a mouse model of endotoxemia. We demonstrated that selective HDAC6 inhibition or knockdown of …

Treatment Of Obesity: Weight Loss And Bariatric Surgery, Bruce M. Wolfe, Elizaveta Walker, Robert H. Eckel

Elizaveta Walker

The Effect Of Sleep Quality And High Intensity Physical Activity On Inflammation And Cardiovascular Disease Risk Factors In College Students, Catherine Abraham

Honors Scholar Theses

Background: Inflammation is the common denominator in chronic conditions such as obesity, diabetes, and depression. While adequate physical activity and optimal sleep quality may help maintain normal inflammation levels, evidence is somewhat conflicting. Aim: This cross-sectional observational study aimed to assess how sleep quality and high intensity physical activity associated with cardiovascular disease (CVD) risk factors and inflammatory biomarkers in a sample of young adults (n=106, ages 18-25 years). Methods: Laboratory-based assessments included lifestyle behaviors (sleep quality, Pittsburgh Sleep Quality Index; self-reported frequency/intensity of physical activity; Healthy Behavior Index derived from reported preference for diet and physical activity), CVD risk …

Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg

Senior Honors Theses

The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease because …

Adiposity Is Associated With Early Reduction In Bone Mass In Pediatric Inflammatory Bowel Disease, Nithya Setty-Shah, Louise S. Maranda, Benjamin U. Nwosu

Benjamin U. Nwosu

Background: The effect of adiposity on bone mass in the early phases of inflammatory bowel disease (IBD) in children and adolescents is unclear.

Aims: To determine the role of adiposity on bone mass in the first 3 years of diagnosis of IBD.

Hypothesis: Increased adiposity will be associated with increased bone mass in both the controls and IBD subjects.

Setting: University tertiary institution.

Methods: Height-adjusted bone mineral density (BMD) z-scores of 25 subjects, age 13.97 ± 2.70y, diagnosed with IBD for < 4 years were compared to 24 controls, age 13.65 ± 2.60y. Overweight was defined as BMI of ≥85^th but <95^th percentile, and obesity as BMI ≥95^thpercentile. Severity of IBD was determined by the Pediatric …

Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type …

Why Is Postoperative Atrial Fibrillation Difficult To Prevent And Treat: Potential Roles Of Unrecognized Magnesium Deficiency And Release Of Ceramide And Platelet-Activating Factor, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Jose Luis Perez-Albela, Bella T. Altura

Touro College of Osteopathic Medicine (Middletown) Publications and Research

Heart failure is a major cause of morbidity and mortality whose costs impose staggering health-care costs and often lengthy hospitalizations. Post-operative atrial fibrillation (POAF) represents a leading cause for heart failure, particularly after cardiac and lung surgeries. Although PAOF is a common cardiac arrhythmia, it is impossible to predict. As the worldwide population is aging, the incidence and prevalence of PAOF is growing. Identifying mechanisms for PAOF is attracting a considerable amount of research with no agreement on the mechanism(s). Our research on the heart and cardiovascular system, over the past 50-plus years, leads us to believe that major causes …

The Anti-Inflammatory Caspase-12 Gene Does Not Influence Sle Phenotype In African-Americans, Trista Fuchs, Jennifer A. Kelly, Emily Simon, Kathy L. Sivils, Evan Hermel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

No abstract provided.

Post-Tbi Hippocampal Neurogenesis In Different Tbi Models, Kaushal S. Patel

Theses and Dissertations

Traumatic brain injury (TBI) leads to short-term and long-term consequences that can cause many different life-long disorders. Studies of TBI have generally focused on the acute stage; however, it is now becoming important to investigate chronic responses following TBI as clinical reports of dementia and cognitive impairments have been linked to a history of TBI. Recent data have established that cognitive function is associated with hippocampal neurogenesis. Chronic injury induced changes in the brain may affect this endogenous process. Chronic responses following TBI include cell death pathways and inflammatory responses that are persistent in the brain for months to years …

Caspase-12, Rheumatoid Arthritis, And The Dog That Didn’T Bark, Evan Hermel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

CASPASE-12 (CASP12) has an anti-inflammatory function during infection. To determine and if CASP12 could protect against inflammatory disease, we investigated the distribution of CASP12 alleles in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 homozygous patients had lower baseline joint narrowing and total disease scores. However, there was no significant difference for distribution of CASP12 genotypes between AA controls and patients with RA, or any other clinical criteria for this disease. CASP12 homozygosity appears to be, at best a subtle protective factor for some aspects of RA in AA patients. This raises an intriguing issue as to how this protein would …

Caspase-12 And Lupus: The Curious Case Of The Dog That Didn’T Bark, Evan Hermel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

CASPASE-12 (CASP12) has an anti-inflammatory function during infection, and is a risk factor for sepsis in African-Americans (AA). To determine if CASP12 could be protective for systemic lupus erythematosus (SLE) in AA, we genotyped AA SLE patients and controls. We found that, at best, there was a weak association between CASP12 genotype with the absence of anti-dsDNA autoantibodies in SLE patients. No effect was seen upon serum interleukin-1 beta levels, nor was any other protective effect noted for the CASP12 genotype, whether upon association with SLE, or any of the 11 American College of Rheumatology classification criteria. We concluded that …

Ppap2b Expression Limits Lesion Formation In Murine Models Of Atherosclerosis, Paul A. Mueller

Theses and Dissertations--Physiology

Coronary artery disease (CAD) is the leading cause of death in both men and women worldwide and is defined as a narrowing of the coronary arteries due to accumulation of atherosclerotic plaques. Genome-wide association studies have identified risk loci within the gene PPAP2B that confers increased risk of developing CAD. Evidence suggests these aforementioned SNPs are regulating PPAP2B expression in a cis-manner through the interruption of transcription factor binding sites. PPAP2B encodes the lipid phosphate phosphatase 3 enzyme that plays a key role in degrading bioactive lysophosphatidic acid (LPA). LPA has a plethora of effects on vascular tissue and is …

Genotoxic Effects Of Magnesium Deficiency In The Cardiovascular System And Their Relationships To Cardiovascular Diseases And Atherogenesis, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Bella T. Altura

The School of Health Sciences Publications and Research

The authors present evidence for a novel, new hypothesis whereby magnesium deficiency (MgD) acts as a genotoxic agent which probably causes numerous, hertofore, unrecognized consequences, even over a short-term, on the physiological, molecular and biochemical machinery of cardiovascular tissues and cells. The end result of these genotoxic effects of MgD probably plays important roles in the etiology and generation of diverse cardiovascular diseases, atherosclerosis, inflammation, and strokes via alterations in the epigenome of cardiovascular tissues and cells. The importance of adequate water-borne and dietary levels of Mg is emphasized.