Medicine and Health Sciences Commons^™

The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun

Center for Translational Medicine Faculty Papers

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo.Wefound that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found …

It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown

MSU Graduate Theses

The protein NOD- like receptor pyrin domain containing 12 (NLRP12) comes from a family of protein receptors with a wide range of functions including fertility as well as anti-inflammatory properties. The biological role of NLRP12 is poorly understood: research on the mechanisms behind its function and/or activation remains contradictory between different cell models. Current research suggests its involvement in a multi-protein complex named the inflammasome. The alternative hypothesis that has also been proposed is that NLRP12 is not a part of the inflammasome, rather it negatively regulates a transcription factor known as NF-��B down stream of Toll-like receptors. NLRP12 is …

Comorbid Metabolic Syndrome And Prodromal Alzheimer's Disease In A Rat Model, Nadezda Ivanova

Electronic Thesis and Dissertation Repository

Metabolic syndrome (MetS), the development of which is associated with high-caloric Western diet intake, represents a risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and appears to contribute to AD progression when MetS and AD are comorbid. The interaction between AD and MetS might be through white matter inflammation, since white matter abnormalities and inflammation are important early events in the etiopathogenesis of both diseases. In these investigations, the effect of a high-caloric diet (HCD), to induce metabolic disturbances, on white matter neuroinflammation and cognitive function was investigated in a transgenic (TG) rat model of prodromal AD …

Single-Cell Glia And Neuron Gene Expression In The Central Amygdala In Opioid Withdrawal Suggests Inflammation With Correlated Gut Dysbiosis, Sean J. O'Sullivan, Evangelia Malahias, James Park, Ankita Srivastava, Beverly A.S. Reyes, Jonathan Gorky, Rajanikanth Vadigepalli, Elisabeth J. Van Bockstaele, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Drug-seeking in opioid dependence is due in part to the severe negative emotion associated with the withdrawal syndrome. It is well-established that negative emotional states emerge from activity in the amygdala. More recently, gut microflora have been shown to contribute substantially to such emotions. We measured gene expression in single glia and neurons gathered from the amygdala using laser capture microdissection and simultaneously measured gut microflora in morphine-dependent and withdrawn rats to investigate drivers of negative emotion in opioid withdrawal. We found that neuroinflammatory genes, notably Tnf, were upregulated in the withdrawal condition and that astrocytes, in particular, were highly …

Macrophages And Associated Inflammation Differentially Impact Obesity, Colorectal Cancer And Obesity-Enhanced Colorectal Cancer, Jackie Bader

Theses and Dissertations

Colorectal Cancer (CRC) is the third-most common malignancy for men or women, with chronic inflammation considered as a primary risk factor. Obesity is also considered a chronic inflammatory disease and is associated with increased CRC incidence. Further, obesity and CRC occur in men and women differently with the highest incidence of either disease found in men, suggesting that female sex hormones may play a protective role in inflammatory diseases. Macrophages can promote inflammation and are a driving force in obesity-associated metabolic dysfunction. Conversely, macrophages also contribute to pro-tumoral responses including, proliferation, angiogenesis and tissue remodeling. This heterogeneity of macrophage behavior …

Role Of Epigenome And Microbiome In Endocannabinoid-Mediated Regulation Of Inflammation During Diet-Induced Obesity, Kathryn Miranda

Theses and Dissertations

Obesity is an inflammatory disease involving accumulation of adipose tissue, gut microbiota dysbiosis, and over-activation of the endocannabinoid system (ECS). Mechanisms involved in ECS regulation of obesity-induced inflammation are not well understood. Presented here are three chapters involving microRNA (miR) regulation of inflammatory adipose tissue macrophages (ATM) during high-fat diet (HFD)-induced obesity and cannabinoid receptor-mediated regulation of gut microbiota dysbiosis.

ATMs are innate immune cells that drive chronic low-grade inflammation during obesity. Polarization between pro-(M1) and anti-(M2-like) inflammatory phenotypes influence insulin sensitivity and energy expenditure; however, the mechanisms involved are unclear. In study one, we characterized miRs involved in ATM …

Modulation Of Inflammation Driven Wound Healing After Glaucoma Surgery, James J. Armstrong

Electronic Thesis and Dissertation Repository

Dysregulated wound healing contributes to most currently unanswered ophthalmological morbidity. Opacification and structure altering contractures compromise the delicate ocular anatomy upon which ocular function and healthy vision are reliant. Glaucoma filtration surgery, corneal stromal injury, proliferative vitreoretinopathy and age-related macular degeneration are major contributors to ocular morbidity – all with myofibroblast transdifferentiation and pathognomonic scarring activity at their core.

This thesis aims to revaluate the means by which dysregulated ocular wound healing is combated with evidence describing a novel strategy to mitigate its effects. A translational approach was used. An initial retrospective analysis of over ten thousand glaucoma surgeries found …

Roles Of Gm-Csf In The Pathogenesis Of Autoimmune Diseases: An Update., Noushin Lotfi, Rodolfo Thome, Nahid Rezaei, Guang-Xian Zhang, Abbas Rezaei, A. M. Rostami, Nafiseh Esmaeil

Department of Neurology Faculty Papers

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was first described as a growth factor that induces the differentiation and proliferation of myeloid progenitors in the bone marrow. GM-CSF also has an important cytokine effect in chronic inflammatory diseases by stimulating the activation and migration of myeloid cells to inflammation sites, promoting survival of target cells and stimulating the renewal of effector granulocytes and macrophages. Because of these pro-cellular effects, an imbalance in GM-CSF production/signaling may lead to harmful inflammatory conditions. In this context, GM-CSF has a pathogenic role in autoimmune diseases that are dependent on cellular immune responses such as multiple sclerosis (MS) …

The Inflammatory Response After Ischemic Stroke: Targeting Β2 And Β1 Integrins, Danielle N. Edwards, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Ischemic stroke is a leading cause of death and disability with limited therapeutic options. Resulting inflammatory mechanisms after reperfusion (removal of the thrombus) result in cytokine activation, calcium influx, and leukocytic infiltration to the area of ischemia. In particular, leukocytes migrate toward areas of inflammation by use of integrins, particularly integrins β₁ and β₂. Integrins have been shown to be necessary for leukocyte adhesion and migration, and thus are of immediate interest in many inflammatory diseases, including ischemic stroke. In this review, we identify the main integrins involved in leukocytic migration following stroke (α_Lβ_{2 …}

Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin

Electronic Theses and Dissertations

Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …

Probiotic Administration As An Adjuvant Therapeutic Treatment For Anxiety, Depression, And Cognitive Impairment Among Hypothyroid Patients, Erin R. Gorman

Selected Honors Theses

Hypothyroidism is a form of thyroid dysfunction that occurs when the thyroid gland does not make and secrete enough thyroid hormones to regulate certain processes in the body. Because thyroid hormones take part in many bodily functions, hypothyroidism can cause a large range of symptoms. Current research indicates that some strains of probiotics have beneficial effects on certain neurological and inflammatory diseases, leading to the impression that they can be used therapeutically for effective treatment of different mental health issues such as anxiety, stress, depression, and impaired memory. Because hypothyroidism often leads to such mental symptoms, it may be possible …

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …

Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, K. R. Lehner, H. A. Silverman, M. E. Adorissio, A. Roy, A. Al-Onaizi, S. S. Chavan, Y. Al-Abed, C. N. Metz, K. J. Tracey, V. A. Paviov, +6 Additional Authors

Journal Articles

No abstract provided.

Irak-4 Rs4251481 Gene Variant: As A Risk Factor On Inflammatory Bowel Disease, Gonca Candan, Resul Kahraman, Hayri̇ye Arzu Ergen

Turkish Journal of Medical Sciences

Background/aim: Abnormal immune response occurs in individuals who have alleles associated with innate and adaptive immune mechanisms that predispose to inflammatory bowel disease (IBD). Interleukin-1 receptor-associated kinase 4 (IRAK-4) involved in the pathway produces cytokines that initiate and maintain inflammation through Toll-like receptors and interleukin-1 receptors on the membranes of innate immune cells are stimulated with antigens. It was aimed to investigate whether IRAK-4 rs3794262 and rs4251481 polymorphisms predispose to IBD and the possible effects of these polymorphisms by examining these gene polymorphisms with the clinic and prognostic parameters of IBD.Material and methods: Real-time PCR technique was used to detect …

Ifn-Γ Stimulated Dental Follicle Mesenchymal Stem Cells Regulate Activated Lymphocyte Response In Rheumatoid Arthritis Patients In Vitro, Noushin Zibandeh, Deni̇z Genç, Güzi̇de Nevsun İnanç, Rafi̇ Haner Di̇reskeneli̇, Tunç Akkoç

Turkish Journal of Medical Sciences

Background/aim: Multipotent mesenchymal stem cells (MSCs) have been investigated in autoimmune diseases such as rheumatoid arthritis (RA) due to their immunomodulatory and regenerative properties. In this study, their immunosuppressive effects on peripheral blood mononuclear cells (PBMC) of RA patients were studied.Materials and methods: Dental follicle stem cells (DFSCs) were isolated from follicle tissue in the orofacial region. Characterization and multipotency analyses were performed. Lymphocytes were isolated from peripheral venous blood of RA patients (n = 5) and healthy individuals (n = 5). DFSCs were preincubated with IFN-γ for 48 h. PBMCs of RA patients and healthy individuals were separately cultured …

Hemophagocytic Lymphohistiocytosis: Epidemiological, Clinical And Biological Profile, Hanane Zahir, Jihane Belkhir, Hanane Mouhib, Mustapha Ait Ameur, Mohammed Chakour

Turkish Journal of Medical Sciences

Background/aim: Hemophagocytic lymphohistiocytosis (HLH) is a clinical, biological, and pathological entity that is rare but has certain morbidity that may be life-threatening. This work aims to establish a focus on the hemophagocytic lymphohistiocytosis and analyze different aspects of diagnosis while emphasizing the biological data.Materials and methods: We report the results of a retrospective study conducted in the hematology department of Avicenna Hospital in Marrakesh. Thirty-one patients with hemophagocytic lymphohistiocytosis were enrolled.Results: The clinical presentation was dominated by fever and deterioration of the general state for almost all our patients. Splenomegaly was objectified in 90% of the patients. Hepatomegaly, lymphadenopathy, and …

Serum Zinc Levels In Seborrheic Dermatitis: A Case-Control Study, Ezgi̇ Aktaş Karabay, Asli Aksu Çerman

Turkish Journal of Medical Sciences

Background/aim:Malassezia colonization, sebaceous gland activity, hormones, immune system defects, environmental factors, and the interactions between these factors are thought to contribute to the pathogenesis of seborrheic dermatitis (SD). Zinc, an essential element, is involved in many biological processes including the ones that contribute to the development of SD. The aim of this study is to evaluate serum zinc levels in patients with SD.Materials and methods: Forty-three patients with SD and 41 healthy controls were enrolled in the study. Disease activity was assessed by the Seborrheic Dermatitis Area and Severity Index by a single dermatologist. Serum zinc levels of all subjects …

Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …

The Effect Of N-Acetylcysteine On Inflammation And Oxidative Stress In Cisplatin-Induced Nephrotoxicity: A Rat Model, İnayet Güntürk, Cevat Yazici, Sema Kader Köse, Fatma Dağli, Bi̇lal Yücel, Arzu Hanim Yay

Turkish Journal of Medical Sciences

Background/Aim: Cisplatin is a highly effective chemotherapeutic agent used in the treatment of solid organ cancers. Besides its chemotherapeutic effectiveness, cisplatin administration is associated with numerous side effects. Of those, the most clinically significant and common effect is nephrotoxicity. Recent studies reported that oxidative stress and inflammation are probably the most important mechanisms that contribute to the nephrotoxicity. N-acetylcysteine (NAC) is an antioxidant and antiinflammatory agent. In the present study, the effects of NAC on cisplatin-induced nephrotoxicity were investigated. Materials and methods: Rats were divided into four groups each including eight rats: CONT, NAC-250, CP, and CP+NAC. Rats in experimental …

Serum Fetuin-A Is Associated With The Components Of Miac(Malnutrition, Inflammation, Atherosclerosis, Calcification) Syndrome In Different Stages, Rüya Mutluay, Ceyla Konca Değerteki̇n, Emel Işiktaş Sayilar, Ülver Deri̇ci̇, Serap Gülteki̇n, Sevi̇m Gönen, Seli̇m Turgay Arinsoy, Mahmut Şükrü Si̇ndel

Turkish Journal of Medical Sciences

Background/aim: Fetuin-A, a circulating inhibitor of calcification, is a marker of inflammatory-nutritional state. We evaluated the association between serum fetuin-A levels and vascular calcification, intima-media thickness, and nutritional and inflammatory markers in different stages of chronic kidney disease (CKD). Materials and methods: CKD patients were sampled for calcium-phosphate parameters and nutritional and inflammatory markers [highly sensitive C-reactive protein (hs-CRP)], and serum fetuin-A levels. Intima-media thicknesses of the common carotid arteries (CIMT) were measured. Peripheral artery calcification scores were obtained.Results: A total of 238 patients were included in the study. Fetuin-A levels in patients with end-stage renal disease were significantly lower …

The Role Of Activin A Signaling In Gastric Reflux-Related Diseases And The Progression To Esophageal Adenocarcinoma, Cedric J. Roudebush

Honors Undergraduate Theses

Gastroesophageal reflux disease (GERD), or acid reflux, affects 6-9 million people in the United States. It is characterized by a reflux of gastric acid and bile salts from the stomach into the esophagus, causing injuries to the esophagus known as Barrett's esophagus (BE). BE is the main risk factor for the development of esophageal adenocarcinoma (EAC), a devastating cancer in the esophagus whose molecular roots remain poorly understood. In recent years, evidence points to the esophageal epithelium itself as responsible for causing and promoting inflammation upon injury by gastric reflux, namely via an increase in inflammatory cytokine secretion. This project …

Dysregulation In The Central Nervous System Upon Mcmv Infection In Newborn Mice, Cathy Yea Won Sung

All ETDs from UAB

Human cytomegalovirus (HCMV) infection is a major cause of morbidity in infants and children throughout the world. Between 0.2-1.2% of all live births is infected with HCMV in the United States. Approximately 5-15% of these newborn babies will develop long-term neurological damage resulting in motor disorders, mental retardation, and sensorineural hearing loss. Although the neurological sequelae associated with congenital HCMV infections are well characterized, little is known about the pathogenesis of the damage to the central nervous system (CNS). To study the pathogenesis of congenital HCMV infection, we have developed a mouse model in which newborn mice are infected intraperitoneally …

Chronic Low Intensity Continuous And Interval Training Prevent Heart Failure-Related Coronary Artery Stiffness, An Ouyang

Theses and Dissertations--Kinesiology and Health Promotion

Heart failure (HF) induced by aortic pressure over-load is associated with increased coronary artery stiffness. Perivascular adipose tissue (PVAT) and advanced glycation end products (AGE) both promote arterial stiffness. However, the mechanisms by which coronary PVAT promotes arterial stiffness and the efficacy of exercise to prevent coronary stiffness are unknown. The present study hypothesized both chronic continuous and interval exercise training would prevent coronary artery stiffness associated with inhibition of PVAT secreted AGE. Yucatan mininature swine were divided into four groups: control-sedentary (CON), aortic-banded sedentary heart failure (HF), aortic-banded HF continuous exercise trained (HF+CONT), and aortic-banded HF interval exercise trained …