Medicine and Health Sciences Commons^™

Adipose-Specific Pparα Knockout Mice Have Increased Lipogenesis By Pask–Srebp1 Signaling And A Polarity Shift To Inflammatory Macrophages In White Adipose Tissue, Terry D. Hinds, Jr., Zachary A. Kipp, Mei Xu, Frederique B. Yiannikouris, Andrew J. Morris, Donald F. Stec, Walter Wahli, David E. Stec

Pharmacology and Nutritional Sciences Faculty Publications

The nuclear receptor PPARα is associated with reducing adiposity, especially in the liver, where it transactivates genes for β-oxidation. Contrarily, the function of PPARα in extrahepatic tissues is less known. Therefore, we established the first adipose-specific PPARα knockout (Ppara^FatKO) mice to determine the signaling position of PPARα in adipose tissue expansion that occurs during the development of obesity. To assess the function of PPARα in adiposity, female and male mice were placed on a high-fat diet (HFD) or normal chow for 30 weeks. Only the male Ppara^FatKO animals had significantly more adiposity in the inguinal white …

Nutrient Intake And Dietary Inflammatory Potential In Current And Recovered Anorexia Nervosa, Olivia Patsalos, Bethan Dalton, Christia Kyprianou, Joseph Firth, Nitin Shivappa Mbbs, Mph, Ph.D., James Hébert Scd, Ulrike Schmidt, Hubertus Himmerich

Faculty Publications

Anorexia nervosa (AN) is characterised by disrupted and restrictive eating patterns. Recent investigations and meta-analyses have found altered concentrations of inflammatory markers in people with current AN. We aimed to assess nutrient intake in participants with current or recovered AN, as compared to healthy individuals, and explore group differences in dietary inflammatory potential as a possible explanation for the observed alterations in inflammatory markers. We recruited participants with current AN (n = 51), those recovered from AN (n = 23), and healthy controls (n = 49). We used the Food Frequency Questionnaire (FFQ), to calculate a Dietary …

Dementia Risk Reduction: Why Haven't The Pharmacological Risk Reduction Trials Worked? An In-Depth Exploration Of Seven Established Risk Factors, Ruth Peters, John Breitner, Sarah James, Gregory A. Jicha, Pierre-Francois Meyer, Marcus Richards, A. David Smith, Hussein N. Yassine, Erin L. Abner, Atticus H. Hainsworth, Patrick G. Kehoe, Nigel Beckett, Christopher Weber, Craig Anderson, Kaarin J. Anstey, Hiroko H. Dodge

Neurology Faculty Publications

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need …

Effects Of Annexin A5 On Endothelial Inflammation Induced By Lipopolysaccharide-Activated Platelets And Extracellular Vesicles, Brent Jeffrey Tschirhart

Electronic Thesis and Dissertation Repository

Sepsis is a dysregulated immune response to infection and the leading cause of mortality globally, accounting for 11 million deaths in 2017. To date, no therapeutics are available to treat the underlying septic response. Previous research from our laboratory has shown that annexin A5 (Anx5) treatment increased survival by 40% in mice with endotoxemia, a model of sepsis. During sepsis, activated platelets release membrane fragments called extracellular vesicles (EVs) with externalization of phosphatidylserine to which annexin A5 binds with a high affinity. We hypothesized that annexin A5 will block the pro-inflammatory response induced by activated platelets and EVs in vascular …

The Role Of Decorin And Biglycan Signaling In Tumorigenesis, Valentina Diehl, Lisa Sophie Huber, Jonel Trebicka, Malgorzata Wygrecka, Renato V. Iozzo, Liliana Schaefer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer …

Arrhythmogenic Hearts In Pkd2 Mutant Mice Are Characterized By Cardiac Fibrosis, Systolic, And Diastolic Dysfunctions, Farideh Amirrad, Rajasekharreddy Pala, Kiumars Shamloo, Brian S. Muntean, Surya M. Nauli

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (PKD) is a hereditary disorder affecting multiple organs, including the heart. PKD has been associated with many cardiac abnormalities including the arrhythmogenic remodeling in clinical evaluations. In our current study, we hypothesized that Pkd2 gene mutation results in structural and functional defects in the myocardium. The structural and functional changes of Pkd2 mutant hearts were analyzed in the myocardial-specific Pkd2 knockout (KO) mouse. We further assessed a potential role of TGF-b₁ signaling in the pathology of Pkd2-KO hearts. Hearts from age-matched 6-month-old MyH6•Pkd2^wt/wt (control or wild-type) and MyH6 …

Inflammation, Oxidative Stress, Insulin Resistance, And Hypertension As Mediators For Adverse Effects Of Obesity On The Brain: A Review, Mahnaz Ghowsi, Farshad Qalekhani, Mohammad Hosein Farzaei, Fariba Mahmudi, Namdar Yousofvand, Tanuj Joshi

BioMedicine

Nowadays, the incidence of obesity is a global challenge and it is estimated that the total number of overweight and obese adults will increase up to 1.35 billion by 2030. Evidence obtained from clinical and experimental studies shows that obesity may be associated with cognitive performance and executive function impairments. Considering various evidence for the poor episodic memory tasks and verbal learning as well as the destruction of cortical gray matter in the obese individuals, here, we collected some causal pathways for contribution of inflammation, oxidative stress, insulin resistance, and hypertension in the development of brain disorders in obesity. The …

Association Between Diet Quality Indices And Incidence Of Type 2 Diabetes In The Melbourne Collaborative Cohort Study, Allison M. Hodge, Md Nazmul Karim, James Hébert Scd, Nitin Shivappa Mbbs, Mph, Ph.D., Barbora De Courten

Faculty Publications

Type 2 diabetes mellitus is a common condition whose incidence is increasing worldwide, and for which obesity and diet are important risk factors. The aim of this study was to assess the association of three diet quality scores with diabetes risk and how much of the association was mediated through body size. The Melbourne Collaborative Cohort Study recruited 41,513 men and women aged 40–69 years during 1990–1994. At baseline, data were collected on lifestyle and diet, anthropometric measures were performed. Incident diabetes was assessed by self-report at follow-up surveys in 1994–1998 and 2003–2007. The associations between the dietary inflammatory index …

Deconstructing Sex Differences In C-Reactive Protein Trends Over Time, Ashley W. Kranjac, Dinko Kranjac, Olivia Lounsbury

Sociology Faculty Articles and Research

Objectives

Heightened inflammatory state, as measured by circulating C-reactive protein (CRP) levels, can promote inflammation-mediated disease risk. It is important to account for population fluctuation and sex variation in serum CRP concentrations on overall time trends.

Methods

Using the National Health and Nutrition Examination Survey data, we specify linear and algebraic decomposition models separately by sex to identify the drivers of the changing trends in the distribution of CRP values in the population.

Results

We found a nonsignificant overall increase in CRP, but a significant decrease among women and increase among men, over a 10-year period. We then used linear …

Β2 Integrin Cd11d/Cd18: From Expression To An Emerging Role In Staged Leukocyte Migration, Eoin N. Blythe, Lynne C. Weaver, Arthur Brown, Gregory A. Dekaban

Paediatrics Publications

CD11d/CD18 is the most recently discovered and least understood β2 integrin. Known CD11d adhesive mechanisms contribute to both extravasation and mesenchymal migration – two key aspects for localizing peripheral leukocytes to sites of inflammation. Differential expression of CD11d induces differences in monocyte/macrophage mesenchymal migration including impacts on macrophage sub-set migration. The participation of CD11d/CD18 in leukocyte localization during atherosclerosis and following neurotrauma has sparked interest in the development of CD11d-targeted therapeutic agents. Whereas the adhesive properties of CD11d have undergone investigation, the signalling pathways induced by ligand binding remain largely undefined. Underlining each adhesive and signalling function, CD11d is under …

The Effects Of Exercise On Inflammatory Biomarkers Over A 36-H Fast, Austin F. Duersch, Bruce W. Bailey, Landon Deru

International Journal of Exercise Science: Conference Proceedings

Postprandial and diet-induced chronic inflammation has become a popular point of discussion over recent years in lifestyle medicine as studies have uncovered the effects that various inflammation markers have on chronic diseases including heart disease, diabetes mellitus, and arthritis. Interventions to help lower inflammation could help promote longevity and decrease risk of chronic diseases. PURPOSE: While previous research has shown various effects of fasting on inflammatory biomarkers, this study assessed the impact of an acute 36h fast with or without exercise at the beginning on inflammatory biomarkers (IL-6, C-peptide, GIP, MCP-1, and TNF-alpha). METHODS: Twenty healthy subjects (11 …

Monoclonal Antibodies Protect Aged Rhesus Macaques From Sars-Cov-2-Induced Immune Activation And Neuroinflammation, Anil Verma, Chase E. Hawes, Yashavanth Shaan Lakshmanappa, Jamin W. Roh, Brian A. Schmidt, Joseph Dutra, William Louie, Hongwei Liu, Zhong Min Ma, Jennifer K. Watanabe, Jodie L. Usachenko, Ramya Immareddy, Rebecca L. Sammak, Rachel Pollard, J. Rachel Reader, Katherine J. Olstad, Lark L. Coffey, Pamela A. Kozlowski, Dennis J. Hartigan-O'Connor, Michel Nussenzweig

School of Graduate Studies Faculty Publications

Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 …

Proteinase 3 Contributes To Endothelial Dysfunction In An Experimental Model Of Sepsis, Eric K. Patterson, Carolina Gillio-Meina, Claudio M. Martin, Douglas D. Fraser, Logan R. Van Nynatten, Marat Slessarev, Gediminas Cepinskas

Paediatrics Publications

In sepsis-induced inflammation, polymorphonuclear neutrophils (PMNs) contribute to vascular dysfunction. The serine proteases proteinase 3 (PR3) and human leukocyte elastase (HLE) are abundant in PMNs and are released upon degranulation. While HLE’s role in inflammation-induced endothelial dysfunction is well studied, PR3’s role is largely uninvestigated. We hypothesized that PR3, similarly to HLE, contributes to vascular barrier dysfunction in sepsis. Plasma PR3 and HLE concentrations and their leukocyte mRNA levels were measured by ELISA and qPCR, respectively, in sepsis patients and controls. Exogenous PR3 or HLE was applied to human umbilical vein endothelial cells (HUVECs) and HUVEC dysfunction was assessed by …

Associations Of Diet With Cardiometabolic And Inflammatory Profiles In Pregnant Women At Risk For Metabolic Complications, Kataryna Jaworsky, Jeffrey L. Ebersole, Petar Planinic, Arpita Basu

Dental Medicine Faculty Publications

Dietary intakes play an important role in the development of metabolic complications during pregnancy. While reported observational studies reveal an inverse association of healthy diets with weight gain, gestational diabetes, and hypertensive complications during pregnancy, there is a paucity of studies conducted among women of specific ethnicities vulnerable to higher risks of pregnancy complications. This is a secondary cross sectional analysis using baseline data from a previously reported clinical trial. We aim to identify associations of maternal habitual dietary intakes with cardiometabolic risks and inflammatory profiles in primarily African American (AA) and Hispanic women in the first half of pregnancy. …

Variations In Er Stress And Unfolded Protein Response Predict Disease Susceptibility, Youwen Zhang

Theses and Dissertations

Numerous studies linked endoplasmic reticulum (ER) stress and unfolded protein response (UPR) to physiological responses to stress and various human pathologies, including metabolic disorders. Although variability in stress responses among individuals has been widely recognized, how such variations in the UPR affect susceptibility to diseases remains unknown. Using outbred deer mice as a model, we explored the consequences of the differential propensity to UPR at the transcriptomic, cellular, and organismic level.

Initially, we analyzed the correlation between several UPR-related genes in primary fibroblasts, at the whole transcriptome level, after ER stress induction. The analysis of correlated transcripts revealed that their …

Aberrantly Low Stat3 And Stat5 Responses Are Associated With Poor Outcome And An Inflammatory Gene Expression Signature In Pediatric Acute Myeloid Leukemia., P Narayanan, T-K Man, R B Gerbing, R Ries, A M Stevens, Y-C Wang, X Long, A S. Gamis, T Cooper, S Meshinchi, T A Alonzo, M S Redell

Manuscripts, Articles, Book Chapters and Other Papers

The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low …

Neuron-Derived Extracellular Vesicles Modulate Microglia Activation And Function, Hui Peng, Brock T. Harvey, Christopher I. Richards, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Microglia act as the immune cells of the central nervous system (CNS). They play an important role in maintaining brain homeostasis but also in mediating neuroimmune responses to insult. The interactions between neurons and microglia represent a key process for neuroimmune regulation and subsequent effects on CNS integrity. However, the molecular mechanisms of neuron-glia communication in regulating microglia function are not fully understood. One recently described means of this intercellular communication is via nano-sized extracellular vesicles (EVs) that transfer a large diversity of molecules between neurons and microglia, such as proteins, lipids, and nucleic acids. To determine the effects of …

Metformin Selectively Dampens The Acute Inflammatory Response Through An Ampk-Dependent Mechanism, Thomas S Postler, Vincent Peng, Dev M Bhatt, Sankar Ghosh

2020-Current year OA Pubs

Metformin is a first-line drug in the treatment of type-2 diabetes mellitus (T2DM). In addition to its antigluconeogenic and insulin-sensitizing properties, metformin has emerged as a potent inhibitor of the chronic inflammatory response of macrophages. In particular, metformin treatment has been shown to reduce expression of interleukin (IL-) 1β during long-term exposure to the pro-inflammatory stimulus lipopolysaccharide (LPS) through a reduction in reactive oxygen species (ROS), which decreases the levels of the hypoxia-inducible factor (HIF) 1-α, and through enhanced expression of IL-10. However, the effect of metformin on the acute inflammatory response, before significant levels of ROS accumulate in the …

Dark Side Of Cancer Therapy: Cancer Treatment-Induced Cardiopulmonary Inflammation, Fibrosis, And Immune Modulation, Boopathi Ettickan, Chellappagounder Thangavel

Department of Dermatology and Cutaneous Biology Faculty Papers

Advancements in cancer therapy increased the cancer free survival rates and reduced the malignant related deaths. Therapeutic options for patients with thoracic cancers include surgical intervention and the application of chemotherapy with ionizing radiation. Despite these advances, cancer therapy-related cardiopulmonary dysfunction (CTRCPD) is one of the most undesirable side effects of cancer therapy and leads to limitations to cancer treatment. Chemoradiation therapy or immunotherapy promote acute and chronic cardiopulmonary damage by inducing reactive oxygen species, DNA damage, inflammation, fibrosis, deregulation of cellular immunity, cardiopulmonary failure, and non-malignant related deaths among cancer-free patients who received cancer therapy. CTRCPD is a complex …

Pulmonary Inflammation And Injury Triggered By Spine Surgery In Recovered Covid-19 Patients Demand Consideration, Luciano Rodrigo Lopes, Silvana Kertzer Kasinski

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Long-Term Treatment With Senolytic Drugs Dasatinib And Quercetin Ameliorates Age-Dependent Intervertebral Disc Degeneration In Mice, Emanuel J Novais, Victoria Tran, Shira N Johnston, Kayla R Darris, Alex J Roupas, Garrett A Sessions, Irving Shapiro, Brian O Diekman, Makarand V Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc degeneration is highly prevalent within the elderly population and is a leading cause of chronic back pain and disability. Due to the link between disc degeneration and senescence, we explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice. We treated C57BL/6 mice beginning at 6, 14, and 18 months of age, and analyzed them at 23 months of age. Interestingly, 6- and 14-month D + Q cohorts show lower incidences of degeneration, and the treatment results in a significant decrease in senescence markers p16INK4a, …

Exercise-Induced Oxidative Stress And Melatonin Supplementation: Current Evidence, Joanna Kruk, Basil Hassan Aboul-Enein, Ewa Duchnik

Health & Wellness Department Faculty Publications and Research

Melatonin possesses the indoleamine structure and exerts antioxidant and anti-inflammatory actions and other physiological properties. Physical exercise can influence secretion of melatonin. Melatonin is used as a natural supplement among athletes to regulate sleep cycles and protect muscles against oxidative damage. Despite decades of research, there is still a lack of a comprehensive and critical review on melatonin supplementation and physical activity relationship. The aim of this literature review is to examine the antioxidant, anti-inflammatory and other biological functions played by melatonin with reference to the effect of physical exercise on melatonin secretion and the effect of this compound supplementation …

Diagnostic Value Of C-Reactive Protein And Soluble Urokinase Plasminogen Activator Receptor In Canine Monocytic Ehrlichiosis, Songul Erdogan, Onur Basbug, Ugur Aydogdu, Serdar Pasa, Hasan Erdogan, Kerem Ural

The Thai Journal of Veterinary Medicine

Canine monocytic ehrlichiosis is a vector-borne disease that can induce renal failure in dogs. In this study we aimed to describe the potential diagnostic efficiency of CRP and suPAR in dogs infected with E. canis and the association between suPAR and CRP with renal failure. For this purpose, the study consisted of a total of 17 dogs, 8 of infected with E. canis and 9 of healty. For evaluating renal failure, plasma urea-creatinine and UPC were determined and also measurements of plasma CRP and suPAR were analysed with ELISA test kits. Mean CRP, suPAR, urea, creatinine and UPC levels of …

Multiple Autonomous Cell Death Suppression Strategies Ensure Cytomegalovirus Fitness, Pratyusha Mandal, Lynsey Nagrani, Liliana Hernandez, Anita Louise Mccormick, Christopher Dillon, Heather Koehler, Linda Roback, Emad S Alnemri, Douglas Green, Edward Mocarski

Department of Biochemistry and Molecular Biology Faculty Papers

Programmed cell death pathways eliminate infected cells and regulate infection-associated inflammation during pathogen invasion. Cytomegaloviruses encode several distinct suppressors that block intrinsic apoptosis, extrinsic apoptosis, and necroptosis, pathways that impact pathogenesis of this ubiquitous herpesvirus. Here, we expanded the understanding of three cell autonomous suppression mechanisms on which murine cytomegalovirus relies: (i) M38.5-encoded viral mitochon-drial inhibitor of apoptosis (vMIA), a BAX suppressor that functions in concert with M41.1-encoded viral inhibitor of BAK oligomerization (vIBO), (ii) M36-encoded viral inhibitor of caspase-8 activation (vICA), and (iii) M45-encoded viral inhibitor of RIP/RHIM activation (vIRA). Following infection of bone marrow-derived macrophages, the virus initially …

Does Epa Cause A Decrease In Inflammation Of Bend.3 Cells Through Ffar4?, Clay J. Weidenhamer

Masters Theses

Atherosclerosis is an inflammatory disease initiated by low and oscillatory shear stress on the endothelium. The inflammatory process recruits leukocytes to the vessel wall by expression of the adhesion molecule VCAM-1. Activation of the NF-κB inflammatory signaling pathway is responsible for the increase in VCM-1 expression. Omega 3 FAs, such as EPA, reduce the risk of atherosclerosis by decreasing this inflammatory response. The pathway by which omega 3 FAs is proposed to inhibit inflammation includes activating FFAR4 to decrease NF-κB activation thereby reducing expression of adhesion molecules. We hypothesized that treatment of endothelial cells with 30 μM EPA would decrease …

Intravesical Cd74 And Cxcr4, Macrophage Migration Inhibitory Factor (Mif) Receptors, Mediate Bladder Pain, Shaojing Ye, Fei Ma, Dlovan F. D. Mahmood, Katherine L. Meyer-Siegler, Raymond E. Menard, David E. Hunt, Lin Leng, Richard Bucala, Pedro L. Vera

Physiology Faculty Publications

BACKGROUND: Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalgesia. Since MIF binds to multiple receptors, we investigated the contribution of individual urothelial MIF receptors to PAR4-induced HMGB1 release in vivo and in vitro and bladder pain in vivo.

METHODOLOGY/PRINCIPAL FINDINGS: We tested the effect of intravesical pre-treatment with individual MIF or MIF receptor (CD74, CXCR4, CXCR2) antagonists on PAR4-induced HMGB1 release in vivo (female C57/BL6 mice) and in vitro (primary …

Tet2 Controls The Responses Of Β Cells To Inflammation In Autoimmune Diabetes., Jinxiu Rui, Songyan Deng, Ana Luisa Perdigoto, Gerald Ponath, Romy Kursawe, Nathan Lawlor, Tomokazu Sumida, Maya Levine-Ritterman, Michael L. Stitzel, David Pitt, Jun Lu, Kevan C Herold

Faculty Research 2021

β cells may participate and contribute to their own demise during Type 1 diabetes (T1D). Here we report a role of their expression of Tet2 in regulating immune killing. Tet2 is induced in murine and human β cells with inflammation but its expression is reduced in surviving β cells. Tet2-KO mice that receive WT bone marrow transplants develop insulitis but not diabetes and islet infiltrates do not eliminate β cells even though immune cells from the mice can transfer diabetes to NOD/scid recipients. Tet2-KO recipients are protected from transfer of disease by diabetogenic immune cells.Tet2-KO β cells show reduced expression …

Associations Between Fasting Duration, Timing Of First And Last Meal, And Cardiometabolic Endpoints In The National Health And Nutrition Examination Survey, Michael David Wirth, Longgang Zhao, Gabrielle Turner-Mcgrievy, Andrew Ortaglia

Faculty Publications

Background: Research indicates potential cardiometabolic benefits of energy consumption earlier in the day. This study examined the association between fasting duration, timing of first and last meals, and cardiometabolic endpoints using data from the National Health and Nutrition Examination Survey (NHANES). Methods: Cross-sectional data from NHANES (2005–2016) were utilized. Diet was obtained from one to two 24-h dietary recalls to characterize nighttime fasting duration and timing of first and last meal. Blood samples were obtained for characterization of C-reactive protein (CRP); glycosylated hemoglobin (HbA1c %); insulin; glucose; and high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol. Survey design procedures …

Effect Of Lactoferrin To Increase Drug Permeability Of Primary Pulmonary Mycobacterial Granulomas, Thao Nguyen, Thao Kt Nguyen

Dissertations & Theses (Open Access)

Despite extensive research and worldwide eradication efforts, Mycobacterium tuberculosis (Mtb) remains a major infectious pathogen to the human population with about 10 million cases of infection per year globally. The host-pathogen interaction, pulmonary granuloma formation, and Mtb adaptions result in increased complexity of the disease. Granulomas are formed by active immune responses generated during Mtb infection, and serve to contain and limit bacterial dissemination. The major mycobacterial surface mycolic acid, trehalose 6,6'-dimycolate (TDM), functions in multiple ways to enhance immune cell recruitment of sites of infection, to induce inflammation and granulomatous responses, and to initiate survival strategies for …

Epithelial Memory Of Resolved Inflammation Limits Tissue Damage While Promoting Pancreatic Tumorigenesis, I-Lin Ho

Dissertations & Theses (Open Access)

Inflammation is a major risk factor for pancreatic ductal adenocarcinoma. When occurring in the context of pancreatitis, mutations of KRAS accelerate tumor development. We discovered that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, epithelial cells of the pancreas display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the prompt reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thus efficiently limiting tissue damage via rapid decrease of zymogen production. We propose that since activating mutations of KRAS …