Medicine and Health Sciences Commons^™

Bioactive Metabolites Of Omega-6 And Omega-3 Fatty Acids Are Associated With Inflammatory Cytokine Concentrations In Maternal And Infant Plasma At The Time Of Delivery, Rebecca Slotkowski, Matthew Van Ormer, Anum Akbar, Taija Hahka, Maranda Thompson, Rebekah Rapoza, Arzu Ulu, Melissa Thoene, Elizabeth Lyden, Maheswari Mukherjee, Ana G. Yuil-Valdes, Sathish Kumar Natarajan, Tara Nordgren, Corrine K. Hanson, Ann Anderson-Berry

Journal Articles: Pediatrics

Background & aims

Inflammation is necessary for a healthy pregnancy. However, unregulated or excessive inflammation during pregnancy is associated with severe maternal and infant morbidities, such as pre-eclampsia, abnormal infant neurodevelopment, or preterm birth. Inflammation is regulated in part by the bioactive metabolites of omega-6 (n-6) and omega-3 (n-3) fatty acids (FAs). N-6 FAs have been shown to promote pro-inflammatory cytokine environments in adults, while n-3 FAs have been shown to contribute to the resolution of inflammation; however, how these metabolites affect maternal and infant inflammation is still uncertain. The objective of this study was to predict the influence of …

Innate And Adaptive Immune System Consequences Of Post-Traumatic Stress Disorder, Tatlock H. Lauten, Tamara Natour, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

In the field of psychiatry, biological markers are rarely, if ever, used in the diagnosis of mental health disorders. Clinicians rely primarily on patient histories and behavioral symptoms to identify specific psychopathologies, which makes diagnosis highly subjective. Moreover, therapies for mental health disorders are aimed specifically at attenuating behavioral manifestations, which overlooks the pathophysiological indices of the disease. This is highly evident in posttraumatic stress disorder (PTSD) where inflammation and immune system perturbations are becoming increasingly described. Further, patients with PTSD possess significantly elevated risks of developing comorbid inflammatory diseases such as autoimmune and cardiovascular diseases, which are likely linked …

Systemic Inflammation Is Associated With Disease Extent And Survival In Oral Cavity Squamous Cell Carcinoma, Brendan Coutu, Dallin N. Christensen, Evan Ryan, Elizabeth Bradford Bell, Weining Zhen, Zafar Sayed

Graduate Medical Education Research Journal

Background: Although systemic immune-inflammation index (SII) correlates with patient survival in various solid malignancies limited information is available in the setting of oral cavity squamous cell carcinoma (OCSCC).

Methods: We retrospectively reviewed 222 patients who underwent a resection of curative intent for patients with OCSCC. SII was determined prior to surgical resection as platelet count × neutrophil count/lymphocyte count.

Results: At a median follow-up of 30.6 months, 2-year disease-free survival (DFS) and overall survival (OS) rates were 63.9% and 76.4%, respectively. A high SII (>1047) was associated with poor performance status and disease extent. A low SII was independently …

Something Smells Fishy: How Lipid Mediators Impact The Maternal-Fetal Interface And Neonatal Development, Maranda Thompson, Arzu Ulu, Maheswari Mukherjee, Ana G. Yuil-Valdes, Melissa K. Thoene, Matthew Van Ormer, Rebecca Slotkowski, Teri Mauch, Ann Anderson-Berry, Corrine K. Hanson, Tara M. Nordgren, Sathish Kumar Natarajan

Journal Articles: Pediatrics

Normal pregnancy relies on inflammation for implantation, placentation, and parturition, but uncontrolled inflammation can lead to poor maternal and infant outcomes. Maternal diet is one modifiable factor that can impact inflammation. Omega-3 and -6 fatty acids obtained through the diet are metabolized into bioactive compounds that effect inflammation. Recent evidence has shown that the downstream products of omega-3 and -6 fatty acids may influence physiology during pregnancy. In this review, the current knowledge relating to omega-3 and omega-6 metabolites during pregnancy will be summarized.

Agricultural Dust Derived Bacterial Extracellular Vesicle Mediated Inflammation Is Attenuated By Dha, Art J. Heires, Derrick R. Samuelson, Daniel Villageliu, Tara M. Nordgren, Debra J. Romberger

Journal Articles: Pulmonary & Critical Care Med

Dietary long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and their pro-resolving metabolites are protective against atherosclerotic disease, and ameliorate systemic inflammatory conditions including lupus erythematosus, psoriasis, and bronchial asthma. Organic bioaerosol inhalation is a common and injurious hazard associated with agricultural occupations such as work in swine concentrated animal feeding operations (CAFOs) and is known to increase the risk for developing respiratory conditions such as asthma and COPD. Nearly all cells secrete membrane-bound vesicles (extracellular vesicles, EVs) that have the capacity to transmit protein, nucleic acid, and lipid signaling mediators between cells. Using a polymer-based isolation technique (ExoQuick, PEG) followed …

Repeated Social Defeat Stress Induces An Inflammatory Gut Milieu By Altering The Mucosal Barrier Integrity And Gut Microbiota Homeostasis, Santosh K. Yadav, Rizwan Ahmad, Cassandra M. Moshfegh, Jagadesan Sankarasubramanian, Vineet A. Joshi, Safwan K. Elkhatib, Yashpal S. Chhonker, Goeffrey A. Talmon, Chittibabu Guda, Adam Case, Amar B. Singh

Journal Articles: Cellular & Integrative Physiology

Background

Posttraumatic stress disorder (PTSD) is a mental health condition triggered by exposure to traumatic events in an individual’s life. Patients with PTSD are also at a higher risk for comorbidities. However, it is not well understood how PTSD affects human health and/or promotes the risk for comorbidities. Nevertheless, patients with PTSD harbor a proinflammatory milieu and dysbiotic gut microbiota. Gut barrier integrity helps to maintain normal gut homeostasis and its dysregulation promotes gut dysbiosis and inflammation.

Methods

We used a mouse model of repeated social defeat stress (RSDS), a preclinical model of PTSD. Behavioral studies, metagenomics analysis of the …

Elevated Crp And Tnf-Α Levels Are Associated With Blunted Neural Oscillations Serving Fluid Intelligence, Sarah M. Dietz, Mikki Schantell, Rachel K. Spooner, Megan E. Sandal, Amirsalar Mansouri, Yasra Arif, Hannah J. Okelberry, Jason A. John, Ryan Glesinger, Pamela E. May, Elizabeth Heinrichs-Graham, Adam J. Case, Matthew C. Zimmerman, Tony W. Wilson

Journal Articles: Cellular & Integrative Physiology

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf.

METHODS: Seventy adults between the ages of 20-66 years …

The Role Of Calprotectin In T-Lymphocyte Driven Inflammation In A Mouse Model Of Psychological Trauma, Cassandra Moshfegh

Theses & Dissertations

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that affects nearly 45 million Americans. This mental disorder is characterized by behavioral symptoms such as learned helplessness, hyperarousal, withdrawal, and flashbacks. The deleterious effects of PTSD are far-reaching and go beyond behavioral dysfunction, as these individuals are at a three-fold higher risk of comorbid inflammatory diseases. Autonomic, metabolic, and cardiovascular diseases plague these individuals later in their lifetime, however, the mechanistic link connecting psychological trauma to this systemic peripheral immunological dysfunction remains elusive. T-lymphocyte-induced inflammation plays a significant role in all these disease pathologies. Previous work from our laboratory demonstrated …

Omega-6 And Omega-3 Fatty Acid-Derived Oxylipins From The Lipoxygenase Pathway In Maternal And Umbilical Cord Plasma At Delivery And Their Relationship With Infant Growth, Maranda Thompson, Arzu Ulu, Ana G. Yuil-Valdes, Maheswari Mukherjee, Melissa K. Thoene, Matthew Van Ormer, Rebecca Slotkowski, Elizabeth Lyden, Ann Anderson-Berry, Corrine K. Hanson, Tara M. Nordgren, Sathish Kumar Natarajan

Journal Articles: Pediatrics

Omega-3 and omega-6 fatty acids are important for neonatal development and health. One mechanism by which omega-3 and omega-6 fatty acids exert their effects is through their metabolism into oxylipins and specialized pro-resolving mediators. However, the influence of oxylipins on fetal growth is not well understood. Therefore, the objective of this study was to identify oxylipins present in maternal and umbilical cord plasma and investigate their relationship with infant growth. Liquid chromatography-tandem mass spectrometry was used to quantify oxylipin levels in plasma collected at the time of delivery. Spearman's correlations highlighted significant correlations between metabolite levels and infant growth. They …

Neutrophil Signaling During Myocardial Infarction Wound Repair, Michael J. Daseke, Upendra Chalise, Mediha Becirovic-Agic, Jeffrey D. Salomon, Leah M. Cook, Adam J. Case, Merry L. Lindsey

Journal Articles: Cellular & Integrative Physiology

Neutrophils are key effector cells of the innate immune system, serving as a first line of defense in the response to injury and playing essential roles in the wound healing process. Following myocardial infarction (MI), neutrophils infiltrate into the infarct region to propagate inflammation and begin the initial phase of cardiac wound repair. Pro-inflammatory neutrophils release proteases to degrade extracellular matrix (ECM), a necessary step for the removal of necrotic myocytes as a prelude for scar formation. Neutrophils transition their phenotype over time to regulate MI inflammation resolution and stabilize scar formation. Neutrophils contribute to the evolution from inflammation to …

The Effect Of Emdogain Periodontal Regenerative Material On Inflammation In Periodontal Maintenance Patients, Jessica M. Gradoville

Theses & Dissertations

The purpose of this double-blinded, randomized, controlled clinical trial was to determine if local application of enamel matrix protein derivative (Emdogain:EMD), combined with minimally-invasive papilla reflection is effective in reducing inflammation in periodontal pockets in patients on periodontal maintenance therapy (PMT).Fifty patients diagnosed with advanced chronic periodontitis presenting with a 6-9mm interproximal probing depth were included in the trial. Experimental (EMD; n=24) and control (saline, n=26) therapies were randomly allocated. Roots were treated with mini-flaps and root planing assisted with endoscope evaluation before EMD or saline application. Inflammation was assessed by bleeding on probing (BOP) at baseline, 6-, and 12-months …

Ovalbumin-Sensitized Mice Have Altered Airway Inflammation To Agriculture Organic Dust, Kristi J. Warren, John D. Dickinson, Amy J. Nelson, Todd A. Wyatt, Debra J. Romberger, Jill A. Poole

Journal Articles: Internal Medicine

Agriculture exposures are associated with reducing the risk of allergy and asthma in early life; yet, repeated exposures later in life are associated with chronic bronchitis and obstructive pulmonary diseases. The objective of this study was to investigate the airway inflammatory response to organic dust extract (ODE) in mice with established ovalbumin (OVA)-induced experimental asthma. C57BL/6 mice were either OVA sensitized/aerosol-exposed or saline (Sal) sensitized/aerosol-challenged. Both groups were then subsequently challenged once with intranasal saline or swine confinement ODE to obtain 4 treatment groups of Sal-Sal, Sal-ODE, OVA-Sal, and OVA-ODE. Airway hyper-responsiveness (AHR) to methacholine, bronchiolar lavage fluid, lung tissues, …

Csf Inflammatory Markers Differ In Gram-Positive Versus Gram-Negative Shunt Infections., Gwenn Skar, David Synhorst, Matthew K. Beaver, Jessica N. Snowden

Journal Articles: Pediatrics

BACKGROUND: Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection.

METHODS: We conducted a retrospective chart review of children with …

Association Between Systemic Inflammation And Nutritional Compounds In Maternal-Infant Dyads, Jessica N. Snowden

Theses & Dissertations

Many events during pregnancy and early infancy can affect infant brain development. Inflammation during pregnancy, around delivery and during early infancy appears to adversely affect infant brain development. As the brain is rapidly growing and developing from conception through early childhood, it is particularly vulnerable during this time to inflammatory insults, which may be exacerbated or ameliorated by nutritional factors. Inflammatory compounds, as well as many nutritional compounds, can be either pro- or anti-inflammatory. These compounds are of particular importance in preterm infants, who are at risk of deficiency in anti-inflammatory micronutrients typically stored as a result of prenatal maternal …

Development Of Macromolecular Prodrugs For The Treatment Of Chronic Inflammatory Pain, Laura Weber

Theses & Dissertations

Chronic pain afflicts millions of people worldwide. Particularly, the inflammatory conditions in the incurable disease rheumatoid arthritis (RA) generate persistent pain in its sufferers, for which a number of different analgesics have been prescribed, such as glucocorticoids (GCs) and opioids. However, administration of these pain- mitigating pharmaceutics is implicated in the development of adverse systemic effects due to their non-specific tissue distribution and quick excretion, eliciting the need for high dosing frequencies. To address this issue, this thesis is focused on the development of prodrugs based on a macromolecular design approach to instill preferential inflammation-targeting and retentive properties to common …

Pancreatic Cancer Associated With Obesity And Diabetes: An Alternative Approach For Its Targeting, Ramesh Pothuraju, Satyanarayana Rachagani, Wade M. Junker, Sanjib Chaudhary, Saraswathi Viswanathan, Sukhwinder Kaur, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Pancreatic cancer (PC) is among foremost causes of cancer related deaths worldwide due to generic symptoms, lack of effective screening strategies and resistance to chemo- and radiotherapies. The risk factors associated with PC include several metabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus (T2DM). Studies have shown that obesity and T2DM are associated with PC pathogenesis; however, their role in PC initiation and development remains obscure.

MAIN BODY: Several biochemical and physiological factors associated with obesity and/or T2DM including adipokines, inflammatory mediators, and altered microbiome are involved in PC progression and metastasis albeit by different …

Induction Of Mir-155 After Brain Injury Promotes Type 1 Interferon And Has A Neuroprotective Effect., Emily Harrison, Kathleen M. Emanuel, Benjamin G. Lamberty, Brenda M. Morsey, Min Li, Matthew L. Kelso, Sowmya V. Yelamanchili, Howard S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

Traumatic brain injury (TBI) produces profound and lasting neuroinflammation that has both beneficial and detrimental effects. Recent evidence has implicated microRNAs (miRNAs) in the regulation of inflammation both in the periphery and the CNS. We examined the expression of inflammation associated miRNAs in the context of TBI using a mouse controlled cortical impact (CCI) model and found increased levels of miR-21, miR-223 and miR-155 in the hippocampus after CCI. The expression of miR-155 was elevated 9-fold after CCI, an increase confirmed by in situ hybridization (ISH). Interestingly, expression of miR-155 was largely found in neuronal nuclei as evidenced by co-localization …

Diabetic Cardiomyopathy: An Immunometabolic Perspective., Paras K. Mishra, Wei Ying, Shyam Sundar Nandi, Gautam K. Bandyopadhyay, Kaushik K. Patel, Sushil K. Mahata

Journal Articles: Cellular & Integrative Physiology

The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM. These early events are followed by steatosis (accumulation of lipid droplets) …

Interleukin (Il)-18 Binding Protein Deficiency Disrupts Natural Killer Cell Maturation And Diminishes Circulating Il-18., Robert Z. Harms, Austin J. Creer, Kristina M. Lorenzo-Arteaga, Katie R. Ostlund, Nora Sarvetnick

Journal Articles: Surgery

The cytokine interleukin (IL)-18 is a crucial amplifier of natural killer (NK) cell function. IL-18 signaling is regulated by the inhibitory effects of IL-18 binding protein (IL-18BP). Using mice deficient in IL-18BP (IL-18BPKO), we investigated the impact of mismanaged IL-18 signaling on NK cells. We found an overall reduced abundance of splenic NK cells in the absence of IL-18BP. Closer examination of NK cell subsets in spleen and bone marrow using CD27 and CD11b expression revealed that immature NK cells were increased in abundance, while the mature population of NK cells was reduced. Also, NK cells were polarized to greater …

A Role For B Cells In Organic Dust Induced Lung Inflammation, Jill A. Poole, Ted R. Mikuls, Michael J. Duryee, Kristi J. Warren, Todd A. Wyatt, Amy J. Nelson, Debra J. Romberger, William W. West, Geoffrey M. Thiele

Journal Articles: Internal Medicine

BACKGROUND: Agriculture organic dust exposures induce lung disease with lymphoid aggregates comprised of both T and B cells. The precise role of B cells in mediating lung inflammation is unknown, yet might be relevant given the emerging role of B cells in obstructive pulmonary disease and associated autoimmunity.

METHODS: Using an established animal model, C57BL/6 wild-type (WT) and B-cell receptor (BCR) knock-out (KO) mice were repetitively treated with intranasal inhalation of swine confinement organic dust extract (ODE) daily for 3 weeks and lavage fluid, lung tissues, and serum were collected.

RESULTS: ODE-induced neutrophil influx in lavage fluid was not reduced …

Effect Of Chemical Pocket Disinfection As An Adjunct To Non-Surgical Maintenance Therapy Of Inflamed Periodontal Pockets, Chad Riggs

Theses & Dissertations

Purpose: Scaling and root planing with adjunctive chemical pocket disinfection (SRP+C) utilizing sodium hypochlorite solution has been used to treat inflamed pockets of periodontal maintenance patients for many years, without evidence of its benefits. The primary objective was to determine if SRP+C is more effective than scaling and root planing alone (SRP) in improving clinical outcomes. The secondary objective was to compare the effect of SRP+C and SRP on pro-inflammatory IL-1β, anti-inflammatory IL-1ra, and anti-inflammatory index (IL-1ra/IL-1β ratio) found in gingival crevicular fluid (GCF).

Materials and Methods: Pockets (≥ 5 mm and BOP) of 31 maintenance patients were included. Test …

Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction By Increasing Interleukin 10., Varun Kesherwani, Vishalakshi Chavali, Bryan T. Hackfort, Suresh C. Tyagi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD) leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and attenuation of anti-inflammatory cytokine such as interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, 8 week old, female C57BL/6J mice were fed with HFD and exercised (swimming …

Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero

Journal Articles: Eppley Institute

The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF) increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that …

Pharmacotherapy For Uveitis: Current Management And Emerging Therapy., Robert J. Barry, Quan Dong Nguyen, Richard W. Lee, Philip I. Murray, Alastair K. Denniston

Journal Articles: Ophthalmology

Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual …

Transcriptional Suppression Of Mir-29b-1/Mir-29a Promoter By C-Myc, Hedgehog, And Nf-Kappab., Justin L. Mott, Satoshi Kurita, Sophie C. Cazanave, Steven F. Bronk, Nathan W. Werneburg, Martin E. Fernandez-Zapico

Journal Articles: Biochemistry & Molecular Biology

MicroRNAs regulate pathways contributing to oncogenesis, and thus the mechanisms causing dysregulation of microRNA expression in cancer are of significant interest. Mature mir-29b levels are decreased in malignant cells, and this alteration promotes the malignant phenotype, including apoptosis resistance. However, the mechanism responsible for mir-29b suppression is unknown. Here, we examined mir-29 expression from chromosome 7q32 using cholangiocarcinoma cells as a model for mir-29b downregulation. Using 5' rapid amplification of cDNA ends, the transcriptional start site was identified for this microRNA locus. Computational analysis revealed the presence of two putative E-box (Myc-binding) sites, a Gli-binding site, and four NF-kappaB-binding sites …