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inflammatory bowl disease

Niloofar Farhang, Jonathan M Brunger, Joshua D Stover, Pratiksha I Thakore, Brandon Lawrence, Farshid Guilak, Charles A Gersbach, Lori A Setton, Robert D Bowles
Musculoskeletal diseases have been associated with inflammatory cytokine action, particularly action by TNF-α and IL-1β. These inflammatory cytokines promote apoptosis and senescence of cells in diseased tissue and extracellular matrix breakdown. Stem cell-based therapies are being considered for the treatment of musculoskeletal diseases, but the presence of these inflammatory cytokines will have similar deleterious action on therapeutic cells delivered to these environments. Methods that prevent inflammatory-induced apoptosis and pro-inflammatory signaling, in cell and pathway specific manners are needed...
January 17, 2017: Tissue Engineering. Part A
Annie C Bowles, Amy L Strong, Rachel M Wise, Robert C Thomas, Brittany Y Gerstein, Maria F Dutreil, Ryan S Hunter, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes...
October 12, 2016: Stem Cells
Talkea Schmidt, Nadine Lorenz, Verena Raker, Sonja Reißig, Ari Waisman, Benno Weigmann, Kerstin Steinbrink
Tolerance to environmental antigens that encounter the organism at interfaces like skin or gut prevents deleterious systemic immune responses. The aim of this study was to analyze whether and how low doses of haptens, by entry through the skin or gastrointestinal tract, affect the outcome of the predominantly Th1/Th17-mediated 2,4,6-trinitro-benzenesulfonic acid-induced colitis, which mimics an autoimmune bowl disease in man. Epicutaneous and oral applications of low doses of the allergen resulted in the induction of low-zone tolerance (LZT) and protected from colitis development, demonstrated by a significantly reduced inflammatory response of the gut in vivo...
September 2016: Journal of Investigative Dermatology
Amy L Strong, Annie C Bowles, Rachel M Wise, Joseph P Morand, Maria F Dutreil, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis is an autoimmune disease that affects the white matter of the central nervous system and involves inflammation and demyelination. The recent advances in our understanding of adipose-derived stromal/stem cells (ASCs) and the utilization of these cells in clinical settings to treat diseases have made it essential to identify the most effective ASCs for therapy. Studies have not yet investigated the impact of obesity on the therapeutic efficacy of ASCs. Obesity is characterized by adipocyte hyperplasia and hypertrophy and can extend to metabolic and endocrine dysfunction...
March 2016: Stem Cells
Barbara P Barna, Matthew McPeek, Anagha Malur, Michael B Fessler, Christopher J Wingard, Larry Dobbs, Kathryn M Verbanac, Mark Bowling, Marc A Judson, Mary Jane Thomassen
We established a murine model of multiwall carbon nanotube (MWCNT)-induced chronic granulomatous disease, which resembles human sarcoidosis pathology. At 60 days after oropharyngeal MWCNT instillation, bronchoalveolar lavage (BAL) cells from wild-type mice exhibit an M1 phenotype with elevated proinflammatory cytokines and reduced peroxisome proliferator-activated receptor γ (PPARγ)-characteristics also present in human sarcoidosis. Based upon MWCNT-associated PPARγ deficiency, we hypothesized that the PPARγ target gene, ATP-binding cassette (ABC) G1, a lipid transporter with antiinflammatory properties, might also be repressed...
June 2016: American Journal of Respiratory Cell and Molecular Biology
Roger B Ruggeri, Leonard Buckbinder, Scott W Bagley, Philip A Carpino, Edward L Conn, Matthew S Dowling, Dilinie P Fernando, Wenhua Jiao, Daniel W Kung, Suvi T M Orr, Yingmei Qi, Benjamin N Rocke, Aaron Smith, Joseph S Warmus, Yan Zhang, Daniel Bowles, Daniel W Widlicka, Heather Eng, Tim Ryder, Raman Sharma, Angela Wolford, Carlin Okerberg, Karen Walters, Tristan S Maurer, Yanwei Zhang, Paul D Bonin, Samantha N Spath, Gang Xing, David Hepworth, Kay Ahn, Amit S Kalgutkar
Myeloperoxidase (MPO) is a heme peroxidase that catalyzes the production of hypochlorous acid. Clinical evidence suggests a causal role for MPO in various autoimmune and inflammatory disorders including vasculitis and cardiovascular and Parkinson's diseases, implying that MPO inhibitors may represent a therapeutic treatment option. Herein, we present the design, synthesis, and preclinical evaluation of N1-substituted-6-arylthiouracils as potent and selective inhibitors of MPO. Inhibition proceeded in a time-dependent manner by a covalent, irreversible mechanism, which was dependent upon MPO catalysis, consistent with mechanism-based inactivation...
November 12, 2015: Journal of Medicinal Chemistry
R E Burgell, A K Asthana, P R Gibson
Ongoing troublesome bowel symptoms despite quiescent inflammatory disease are a frequent management challenge when caring for patients with inflammatory bowel disease (IBD). Even when active disease has been excluded the prevalence of residual gastrointestinal symptoms is surprisingly high and the cause often obscure. The presence of a concurrent functional disorder such as irritable bowel syndrome (IBS) is associated with worse quality of life, worse physical functioning, higher prevalence of anxiety and greater health care utilization...
December 2015: Minerva Gastroenterologica e Dietologica
Jiazhuo Wang, John D MacKenzie, Rageshree Ramachandran, Danny Z Chen
Identifying neutrophils lays a crucial foundation for diagnosing acute inflammation diseases. But, such computerized methods on the commonly used H&E staining histology tissue images are lacking, due to various inherent difficulties of identifying cells in such image modality and the challenge that a considerable portion of neutrophils do not have a "textbook" appearance. In this paper, we propose a new method for identifying neutrophils in H&E staining histology tissue images. We first segment the cells by applying iterative edge labeling, and then identify neutrophils based on the segmentation results by considering the "context" of each candidate cell constructed by a new Voronoi diagram of clusters of other neutrophils...
2014: Medical Image Computing and Computer-assisted Intervention: MICCAI ..
Annie C Bowles, Brittni A Scruggs, Bruce A Bunnell
Multiple sclerosis (MS) is a common neurodegenerative disease that presents after an auto-reactive immune response against constituents of the central nervous system. Demyelination, inflammation, and white matter lesions are all hallmarks of this disease. Clinical research supports the use of mesenchymal stem cells (MSCs) as therapy for MS to ameliorate symptoms and pathology. MSCs can be isolated from multiple tissues, including adipose and bone marrow, and are able to migrate to sites of pathology, release anti-inflammatory factors, and provide immunomodulatory and neuroprotective effects once administered...
2014: Methods in Molecular Biology
Meaghan R Bowling, Dongqi Xing, Akash Kapadia, Yiu-Fai Chen, Alexander J Szalai, Suzanne Oparil, Fadi G Hage
OBJECTIVE: 17β-Estradiol (E2) offers cardiovascular protection in young female animals and postmenopausal women. In contrast, randomized trials of menopausal hormones performed in older women have shown harm or no cardiovascular benefit. We hypothesize that E2 effects on vascular inflammation are age dependent. APPROACH AND RESULTS: Young (10 weeks) and aged (52 weeks) female C57BL/6 mice were used as source for primary cultures of bone marrow-derived macrophages (BMMs) and vascular smooth muscle cells (VSMCs)...
July 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
Jacques Moreau
Extremely variable in their clinical expression, inflammatory bowl diseases evolve by flare-ups interspersed with phases of remission. Complications can be severe, sometimes requiring surgery. While treatments have evolved considerably, therapeutic patient education plays an important role in the therapeutic approach.
March 2014: Revue de L'infirmière
Xiujuan Zhang, Annie C Bowles, Julie A Semon, Brittni A Scruggs, Shijia Zhang, Amy L Strong, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis (MS), characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs) for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE), a murine model of MS...
2014: PloS One
Fuat Hakan Saner, Knut Nowak, Dieter Hoyer, Peter Rath, Ali Canbay, Andreas Paul, Michael Koldehoff, Ahmet Elmaağaclı
BACKGROUND: Infections after liver transplantation are the main cause of death in the first year. Recent reports indicate that NOD2 gene mutations increase the risk for inflammatory bowl disease and the severity of graft-versus-host disease in bone marrow transplant patients. Data on polymorphisms in liver transplant patients are sparse. We analyzed 13 single-nucleotide polymorphisms (SNPs) of 13 different gene variants including the SNPs of NOD2 genes from liver recipients. The aim of the study was to evaluate the impact of the SNPs on dialysis-dependent kidney failure, the incidence of infections and patient survival...
2014: BMC Gastroenterology
Brittni A Scruggs, Xiujuan Zhang, Annie C Bowles, Peter A Gold, Julie A Semon, Jeanne M Fisher-Perkins, Shijia Zhang, Ryan W Bonvillain, Leann Myers, Su Chen Li, Allan V Kalueff, Bruce A Bunnell
Globoid cell leukodystrophy (GLD) is a common neurodegenerative lysosomal storage disorder caused by a deficiency in galactocerebrosidase (GALC), an enzyme that cleaves galactocerebroside during myelination. Bone marrow transplantation has shown promise when administered to late-onset GLD patients. However, the side effects (e.g., graft vs. host disease), harsh conditioning regimens (e.g., myelosuppression), and variable therapeutic effects make this an unsuitable option for infantile GLD patients. We previously reported modest improvements in the twitcher mouse model of GLD after intracerebroventricular (ICV) injections of a low-dose of multipotent stromal cells (MSCs)...
August 2013: Stem Cells
Matthew W Foster, J Will Thompson, Michael T Forrester, Yonggang Sha, Timothy J McMahon, Dawn E Bowles, M Arthur Moseley, Harvey E Marshall
The cytokine-inducible isoform of nitric oxide synthase (NOS2) is constitutively expressed in human respiratory epithelia and is upregulated in inflammatory lung disease. Here, we sought to better define the protein interactions that may be important for NOS2 activity and stability, as well as to identify potential targets of NOS2-derived NO, in the respiratory epithelium. We overexpressed Flag-tagged, catalytically-inactive NOS2 in A549 cells and used mass spectrometry to qualitatively identify NOS2 co-immunoprecipitating proteins...
November 1, 2013: Nitric Oxide: Biology and Chemistry
Hyun Jeong Lee, Mi Yong Rha, Young Yun Cho, Eun Ran Kim, Dong Kyung Chang
The objective of this article is to report improvement of nutritional status by protein supplements in the patient with protein-losing enteropathy. The patient was a female whose age was 25 and underwent medical treatment of Crohn's disease, an inflammatory bowl disease, after diagnosis of cryptogenic multifocal ulcerous enteritis. The weight was 33.3 kg (68% of IBW) in the severe underweight and suffered from ascites and subcutaneous edema with hypoalbuminemia (1.3 g/dL) at the time of hospitalization. The patient consumed food restrictively due to abdominal discomfort...
July 2012: Clinical Nutrition Research
Isabelle Masseau, Michael J Davis, Douglas K Bowles
INTRODUCTION: Reduction of vascular inflammation might contribute to the beneficial effects of exercise. We hypothesized that 1) exercise would reduce carotid endothelial vascular cell adhesion molecule-1 (VCAM-1) and that 2) in vivo detection of carotid inflammation can be achieved in a large animal model using contrast-enhanced ultrasound (CEU) with VCAM-1-targeted microbubbles (MBs). METHODS: Familial hypercholesterolemic (FH) swine were divided into sedentary (Sed) and exercise-trained (Ex) groups...
December 2012: Medicine and Science in Sports and Exercise
Lawrence N Barrera, Stuart A Rushworth, Kristian M Bowles, David J MacEwan
Multiple myeloma (MM) is a progressive malignant disorder characterized by accumulation of plasma cells in the bone marrow. MM remains an incurable disease with a 5-y survival rate of approximately 40%. While clinical response rates to first line chemotherapeutics are high, disease relapse is inevitable, and occurs because a small fraction of the original myeloma cells appear to be resistant to treatment. Heme oxygenase-1 (HO-1) is an Nrf2 transcription factor-regulated gene that is commonly induced following oxidative stress and cellular injury, functioning to decrease oxidative stress and inflammatory responses, protecting against apoptosis and altering the cell cycle...
June 15, 2012: Cell Cycle
Frank L Bowling, Sanjay U Dissanayake, Edward B Jude
Accurate identification of infection in diabetic foot lesions is essential as the alternative can result in complicated medical and/or surgical interventions. The aim should be the differentiation between colonization and infection to avoid premature initiation of antimicrobial therapy. Diabetic foot ulcers provide a suitable environment for a diversity of microorganisms to first contaminate then subsequently colonize the wound. Infection can occur when a pathogenic factor produced by one or more microorganisms exceeds the capacity of the host immune system causing tissue damage and triggering both local and systemic inflammatory responses...
May 2012: Current Diabetes Reviews
Shogo Tokuyama, Kazuo Nakamoto
Fatty acids, which are the essential nutrients for humans, are an important source of energy and an essential component of cell membranes. They also function as signal transduction molecules in a range of biological phenomena. Recently, an increasing number of physiologic and pharmacologic reports on fatty acids have improved our understanding of the association of fatty acids with certain diseases. It has also become apparent that functional properties of fatty acids are modulated by factors such as the amount of individual fatty acid intake and their distribution among organs...
2011: Biological & Pharmaceutical Bulletin
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