Medicine and Health Sciences Commons^™

Cerebrospinal Fluid Kynurenine And Kynurenic Acid Concentrations Are Associated With Coma Duration And Long-Term Neurocognitive Impairment In Ugandan Children With Cerebral Malaria, Dag Holmberg, Elisabeth Franzén-Röhl, Richard Idro, Robert Opoka, Paul Bangirana, Carl Sellgren, Anna Färnert, Lilly Schwieler, Göran Engberg, Chandy John

Paediatrics and Child Health, East Africa

Background: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated.

Methods: Cerebrospinal fuid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were compared to …

Deficiency Of Klf4 Compromises The Lung Function In An Acute Mouse Model Of Allergic Asthma, Jeanette A. Nimpong, Wintana Gebregziabher, Udai P. Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Johnie Hodge, Chunming Liu, Daping Fan, Walden Ai

Molecular and Cellular Biochemistry Faculty Publications

Asthma is a chronic inflammatory disease of the airways and the mechanisms are not fully understood. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of monocytes, granulocyte and myeloid cells at early stage of differentiation. They possess phenotypic plasticity and regulate airway inflammation. We recently reported that Kruppel-like factor 4 (KLF4) regulates MDSC differentiation into fibrocytes, emerging effectors in chronic inflammation. However, the role of KLF4 in asthma is not known. Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine and a key initiator of allergic airway inflammation. Given the fact that TSLP promotes Th2 cytokine production that increases MDSC …

Pro-Inflammatory Chemokines And Cytokines Dominate The Blister Fluid Molecular Signature In Patients With Epidermolysis Bullosa And Affect Leukocyte And Stem Cell Migration., Vitali Alexeev, Julio Cesar Salas-Alanis, Francis Palisson, Lila Mukhtarzada, Giulio Fortuna, Jouni Uitto, Andrew P. South, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

Hereditary epidermolysis bullosa (EB) is associated with skin blistering and the development of chronic nonhealing wounds. Although clinical studies have shown that cell-based therapies improve wound healing, the recruitment of therapeutic cells to blistering skin and to more advanced skin lesions remains a challenge. Here, we analyzed cytokines and chemokines in blister fluids of patients affected by dystrophic, junctional, and simplex EB. Our analysis revealed high levels of CXCR1, CXCR2, CCR2, and CCR4 ligands, particularly dominant in dystrophic and junctional EB. In vitro migration assays demonstrated the preferential recruitment of CCR4⁺ lymphocytes and CXCR1⁺, CXCR2⁺, …

Timing Of Pd-1 Blockade Is Critical To Effective Combination Immunotherapy With Anti-Ox40., David J Messenheimer, Shawn M. Jensen, Michael E Afentoulis, Keith W Wegman, Zipei Feng, David J Friedman, Michael J. Gough, Walter Urba, Bernard A Fox

Articles, Abstracts, and Reports

Purpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.Experimental Design: We utilized an anti-PD-1-refractory, orthotopically transplanted MMTV-PyMT mammary cancer model to investigate the antitumor effect of an agonist anti-OX40 antibody combined with anti-PD-1. As PD-1 naturally aids in immune contraction after T-cell activation, we treated mice with concurrent combination treatment versus sequentially administering anti-OX40 …

Biological Markers For Pulpal Inflammation: A Systematic Review., Dan-Krister Rechenberg, Johnah C. Galicia, Ove A. Peters

Ove Peters

BACKGROUND AND OBJECTIVE: Pulpitis is mainly caused by an opportunistic infection of the pulp space with commensal oral microorganisms. Depending on the state of inflammation, different treatment regimes are currently advocated. Predictable vital pulp therapy depends on accurate determination of the pulpal status that will allow repair to occur. The role of several players of the host response in pulpitis is well documented: cytokines, proteases, inflammatory mediators, growth factors, antimicrobial peptides and others contribute to pulpal defense mechanisms; these factors may serve as biomarkers that indicate the status of the pulp. Therefore, the aim of this systematic review was to …

Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas

Pharmacy Faculty Articles and Research

Background: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer’s disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.

Methods: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) …

The Trophic Life Cycle Stage Of The Opportunistic Fungal Pathogen Pneumocystis Murina Hinders The Ability Of Dendritic Cells To Stimulate Cd4+ T Cell Responses, Heather M. Evans, Andrew Simpson, Shu Shen, Arnold J. Stromberg, Carol L. Pickett, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding …

Dietary Inflammatory Index And Colorectal Cancer Risk – A Meta-Analysis, Nitin Shivappa, Justyna Godos, James R. Hébert, Michael David Wirth, Gabriele Piuri, Attilio Speciani, Giuseppe Grosso

Faculty Publications

Diet and chronic inflammation of the colon have been suggested to be risk factors in the development of colorectal cancer (CRC). The possible link between inflammatory potential of diet, measured through the Dietary Inflammatory Index (DII®), and CRC has been investigated in several populations across the world. The aim of this study was to conduct a meta-analysis on studies exploring this association. Data from nine studies were eligible, of which five were case-control and four were cohort studies. Results from meta-analysis showed a positive association between increasing DII scores, indicating a pro-inflammatory diet, and CRC. Individuals in the highest versus …

Anti-Inflammatory Homoeopathic Drug Dilutions Restrain Lipopolysaccharide-Induced Release Of Pro-Inflammatory Cytokines: In Vitro And In Vivo Evidence, Umesh Mahajan, Ajit Walke, Mahendra Kardile, Sameer Goyal, Sumit Siddharth, Chanakya Kundu, Shreesh Ojha, Chandragouda Patil

Indian Journal of Research in Homoeopathy

Context: The lipopolysaccharide (LPS)-induced cytokine release and oxidative stress are validated experimental parameters used to test anti-inflammatory activity. We investigated the effects of homoeopathic mother tinctures, 6 CH, 30 CH and 200 CH dilutions of Arnica montana, Thuja occidentalis and Bryonia alba against LPS (1 μg/ml)-induced cytokine release from RAW-264.7 cells and human whole-blood culture. Materials and Methods: For in vivo evaluations, mice were orally treated with 0.1 ml drug dilutions twice a day for 5 days followed by an intraperitoneal injection of 0.5 mg/kg LPS. After 24 h, the mice were sacrificed and serum levels of pro-inflammatory cytokines and …

Cumulative Trauma, Emotion Reactivity And Salivary Cytokine Response Following Acute Stress Among Healthy Women., Yvette Z. Szabo

Electronic Theses and Dissertations

This study furthers understanding of how trauma exposure may be connected to the development and maintenance of poor health by focusing on cytokines, tightly regulated proteins of the immune system. Cytokine responses to acute stress have been associated with the onset of poorer mental health in physically healthy women. The present study examined how two factors recently associated with cytokine reactivity –cumulative trauma and emotion reactivity– are associated with salivary cytokine reactivity among healthy women. Seventy-one women, screened to be physically and mentally healthy, completed a laboratory acute stress paradigm and self-report measures of state emotion and trauma exposure. Participants …

Peripheral Inflammation, Apolipoprotein E4, And Amyloid-Β Interact To Induce Cognitive And Cerebrovascular Dysfunction, Felecia M. Marottoli, Yuriko Katsumata, Kevin P. Koster, Riya Thomas, David W. Fardo, Leon M. Tai

Biostatistics Faculty Publications

Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer’s disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 (APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo. EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of …

Pro And Anti-Inflammatory Cytokine Levels (Tnf- , Il-1 , Il-6 Andil-10) In Rat Model Of Neuroma, Junad Khan, Noboru Noma, Andrew L. Young, Davis Thomas

Andrew L. Young

Traumatic neuroma is neuronal tissue proliferation developed in a nerve injury site, often associatedwith increased sensitivity and spontaneous or evoked neuropathic pain. The mechanisms leading to the disorganized nerve proliferation are not completely understood, though inflammation in the injured nerve vicinity most likely has a role in the process. Inflammatory cytokines are also known to be involvedin the maintenance and development of post-traumatic and neuropathic pain. The goal of this study wasto quantify and compare pro and anti-inflammatory cytokines (TNF- , IL-1 , IL-6 and IL-10) levels innerves that formed neuromas and nerves that did not, following sciatic nerve transection. …

Neurological Consequences Of Systemic Inflammation In The Premature Neonate, Aparna Patra, Hong Huang, John A. Bauer, Peter J. Giannone

Pediatrics Faculty Publications

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of …

Mk2 Promotes Colorectal Cancer Development, Invasion, And Growth Through Mk2-Induced Cytokines, Anita Lynne Ray

Biomedical Sciences ETDs

Colorectal cancer (CRC) is the third most common malignancy in the United States for men and women. A major risk factor for CRC development and progression is inflammation, in particular the inflammatory cytokines IL-1, IL-6, and TNF-α. These proteins promote critical cancer functions, such as proliferation, invasion, survival, and migration. Control of inflammation is one potential area of therapeutic intervention for some cancers. Because signaling of these cytokines overlaps in many of the same pathways, targets upstream of protein production could prove an effective strategy to reduce inflammation. MAPK-activated protein kinase 2 (MK2) pathway controls production of these cytokines within …

Palatal Mucosa Derived Fibroblasts Present An Adaptive Behavior Regarding Cytokine Secretion When Grafted Onto The Gingival Margin, Fabíola Pontes Azevedo, Ana Carolina Morandini, Carla Renata Sipert, Thiago José Dionísio, Carlos Ferreira Santos, Carla Andreotti Damante, Maria Lúcia Rubo De Rezende, Adriana Campos Passanezi Sant'ana, Sebastião Luiz Aguiar Greghi

Ana Carolina Morandini

BACKGROUND: Considering that grafted gingival tissue might have to be adapted to the receptor area and that fibroblasts have the ability to respond to bacterial stimuli through the release of various cytokines, this study investigated whether fibroblasts from the palatal mucosa behave differently when grafted onto the gingival margin regarding cytokine secretion. METHODS: Biopsies from the palatal mucosa were collected at the time of free gingival graft surgery, and after four months re-collection was performed upon surgery for root coverage. Fibroblasts were isolated by the explant technique, cultured and stimulated with Porphyromonas gingivalis (Pg) and Escherichia coli (Ec) LPS for …

Nfatc2 Modulates Microglial Activation In The Aβpp/Ps1 Mouse Model Of Alzheimer's Disease, Gunjan D. Manocha, Atreyi Ghatak, Kendra L. Puig, Susan D. Kraner, Christopher M. Norris, Colin K. Combs

Pharmacology and Nutritional Sciences Faculty Publications

Alzheimer’s disease (AD) brains are characterized by fibrillar amyloid-β (Aβ) peptide containing plaques and associated reactive microglia. The proinflammatory phenotype of the microglia suggests that they may negatively affect disease course and contribute to behavioral decline. This hypothesis predicts that attenuating microglial activation may provide benefit against disease. Prior work from our laboratory and others has characterized a role for the transcription factor, nuclear factor of activated T cells (NFAT), in regulating microglial phenotype in response to different stimuli, including Aβ peptide. We observed that the NFATc2 isoform was the most highly expressed in murine microglia cultures, and inhibition or …

Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8, …

A Novel Agonist Of The Trif Pathway Induces A Cellular State Refractory To Replication Of Zika, Chikungunya, And Dengue Viruses., Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason R Baird, Michael J. Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R Defilippis

Articles, Abstracts, and Reports

The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread. In light of this strategy's potential, we undertook a screen to identify novel interferon-activating small molecules. Here, we describe …

Cannabinoid Receptor 2 (Cb2) Ligands Downregulate Pro-Inflammatory Markers In Stimulated Primary Human Periodontal Ligament Fibroblasts (Hpdlfs), Ammaar Hasan Abidi

Theses and Dissertations (ETD)

There are approximately 743 million individuals suffering from chronic periodontitis (PD) making it the sixth most prevalent condition worldwide. The affected adult population in the U.S. are nearly 64.7 million and the healthcare costs exceeds $14 billion. Recently, host response to pathogenic infection has been seen critical to the progression of PD and exhibit increase in various inflammatory markers. Marijuana is well known for its recreational usage and is a risk factor for periodontal disease, which is seen as a concern in society for its negative health consequences. However, many medical conditions can benefit from the pharmacological effects of cannabinoids. …

Induction And Characterization Of Anti-Tumor Endothelium Immunity Elicited By Vallovax Therapeutic Cancer Vaccine., Samuel C Wagner, Thomas E Ichim, Vladimir Bogin, Wei-Ping Min, Francisco Silva, Amit N Patel, Santosh Kesari

Articles, Abstracts, and Reports

ValloVax is a placental endothelium derived vaccine which induces tissue-nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate mechanisms of action, we showed that production of ValloVax, which involves treating placental endothelial cells with IFN-gamma, results in upregulation of HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction, ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from ValloVax immunized mice was capable of killing in vitro tumor-like endothelium but not control endothelium. Using defined antigens associated with tumor endothelial cells, specific molecular entities were identified as being targeted by ValloVax induced antibodies. Binding of predominantly IgG …

Pro And Anti-Inflammatory Cytokine Levels (Tnf- , Il-1 , Il-6 Andil-10) In Rat Model Of Neuroma, Junad Khan, Noboru Noma, Andrew L. Young, Davis Thomas

All Dugoni School of Dentistry Faculty Articles

Traumatic neuroma is neuronal tissue proliferation developed in a nerve injury site, often associatedwith increased sensitivity and spontaneous or evoked neuropathic pain. The mechanisms leading to the disorganized nerve proliferation are not completely understood, though inflammation in the injured nerve vicinity most likely has a role in the process. Inflammatory cytokines are also known to be involvedin the maintenance and development of post-traumatic and neuropathic pain. The goal of this study wasto quantify and compare pro and anti-inflammatory cytokines (TNF- , IL-1 , IL-6 and IL-10) levels innerves that formed neuromas and nerves that did not, following sciatic nerve transection. …

Retention Of Normal Glia Function By An Isoform-Selective Protein Kinase Inhibitor Drug Candidate That Modulates Cytokine Production And Cognitive Outcomes, Zhengqiu Zhou, Adam D. Bachstetter, Claudia B. Späni, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Background: Brain p38α mitogen-activated protein kinase (MAPK), a potential therapeutic target for cognitive dysfunction based on the neuroinflammation-synaptic dysfunction cycle of pathophysiology progression, offers an innovative pharmacological strategy via inhibiting the same activated target in both glia and neurons, thereby enhancing the possibility for efficacy. The highly selective, brain-penetrant p38αMAPK inhibitor MW150 attenuates cognitive dysfunction in two distinct Alzheimer's disease (AD)-relevant models and avoids the problems encountered with previous mixed-kinase inhibitor drug candidates. Therefore, it is essential that the glial effects of this CNS-active kinase inhibitor be addressed in order to anticipate future use in clinical investigations.

Methods: …

Oncolog, Volume 62, Number 04, April 2017, Bryan Tutt, Sarah Bronson

OncoLog MD Anderson's Report to Physicians (All issues)

• Advances in Surgical Management of Lymphedema: New options reduce edema in limbs, improve quality of life for cancer patients with lymphedema.
• Noncytotoxic First-Line Therapy for Mantle Cell Lymphoma: First-line therapy with targeted and immunotherapy agents produces high response rates in mantle cell lymphoma.
• Reports from the Survivorship Research Symposium: Research on BK virus, heart failure, and aspiration in cancer survivors.
• HOUSE CALL: Types of Immunotherapy for Cancer: Understanding different approaches to immunotherapy

Melatonin Modulates Inflammatory Response And Suppresses Burn-Induced Apoptotic Injury, Ganka Bekyarova, Milena Atanasova, Maria Tzaneva, Anelia Dimitrova

Journal of Mind and Medical Sciences

Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p.) was applied immediately after 30% of total body surface area (TBSA) burns on male Wistar rats. The level of malondialdehyde (MDA) as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry …

Neutralizing Anti-Interleukin-1Β Antibodies Reduce Ischemia-Related Interleukin-1Β Transport Across The Blood-Brain Barrier In Fetal Sheep, Aparna Patra, Xiaodi Chen, Grazyna B. Sadowska, Jiyong Zhang, Yow-Pin Lim, James F. Padbury, William A. Banks, Barbara S. Stonestreet

Pediatrics Faculty Publications

Hypoxic ischemic insults predispose to perinatal brain injury. Pro-inflammatory cytokines are important in the evolution of this injury. Interleukin-1β (IL-1β) is a key mediator of inflammatory responses and elevated IL-1β levels in brain correlate with adverse neurodevelopmental outcomes after brain injury. Impaired blood-brain barrier (BBB) function represents an important component of hypoxic-ischemic brain injury in the fetus. In addition, ischemia-reperfusion increases cytokine transport across the BBB of the ovine fetus. Reducing pro-inflammatory cytokine entry into brain could represent a novel approach to attenuate ischemia-related brain injury. We hypothesized that infusions of neutralizing IL-1β monoclonal antibody (mAb) reduce IL-1β transport across …

Metabolic And Molecular Insights Into An Essential Role Of Nicotinamide Phosphoribosyltransferase., Li Q. Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P. Heruth, Chengpeng Bi, R Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N. Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of NAMPT in these physiological and pathological processes are not fully understood. Here, we provide experimental evidence that a Nampt gene homozygous knockout (Nampt-/-) resulted in lethality at an early stage of mouse embryonic development and death within 5-10 days in adult mice accompanied by a 25.24±2.22% body weight loss, after the tamoxifen induction of NamptF/F × Cre mice. These results substantiate that Nampt …

Role Of Cytokines And Chemokines In Alcohol-Induced Tumor Promotion, Danlei Chen, Fengyun Zhang, Haifeng Ren, Jia Luo, Siying Wang

Pharmacology and Nutritional Sciences Faculty Publications

Excessive chronic alcohol consumption has become a worldwide health problem. The oncogenic effect of chronic alcohol consumption is one of the leading concerns. The mechanisms of alcohol-induced tumorigenesis and tumor progression are largely unknown, although many factors have been implicated in the process. This review discusses the recent progress in this research area with concentration on alcohol-induced dysregulation of cytokines and chemokines. Based on the available evidence, we propose that alcohol promotes tumor progression by the dysregulation of the cytokine/chemokine system. In addition, we discuss specific transcription factors and signaling pathways that are involved in the action of these cytokines/chemokines …

Transcriptomic Effects Of Adenosine 2a Receptor Deletion In Healthy And Endotoxemic Murine Myocardium, Kevin J. Ashton, Melissa E. Reichelt, S. Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M. D. Delbridge, Polly A. Hofmann, R. Ray Morrison, John P. Headrick

Clinical and Translational Science Institute

Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 >% FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2. Few canonical paths were impacted, with altered Gnb1, Prkar2b, Pde3b and Map3k2 (among others) implicating modified G protein/cAMP/PKA and …

Interleukin-1 Receptor Antagonist Polymorphism And Birth Timing: Pathway Analysis Among African American Women, Shannon L. Gillespie, Jeremy L. Neal, Lisa Christian, Laura A. Szalacha, Donna O. Mccarthy, Pamela J. Salsberry

College of Nursing Faculty Research and Publications

Background: Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking.

Objectives: We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or …

Neuroinflammatory And Cognitive Consequences Of Combined Radiation And Immunotherapy In A Novel Preclinical Model., Gwendolyn J Mcginnis, David Friedman, Kristina H Young, Eileen Ruth S Torres, Charles R Thomas, Michael J Gough, Jacob Raber

Articles, Abstracts, and Reports

BACKGROUND: Cancer patients often report behavioral and cognitive changes following cancer treatment. These effects can be seen in patients who have not yet received treatment or have received only peripheral (non-brain) irradiation. Novel treatments combining radiotherapy (RT) and immunotherapy (IT) demonstrate remarkable efficacy with respect to tumor outcomes by enhancing the proinflammatory environment in the tumor. However, a proinflammatory environment in the brain mediates cognitive impairments in other neurological disorders and may affect brain function in cancer patients receiving these novel treatments. Currently, gaps exist as to whether these treatments impact the brain in individuals with or without tumors and …