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Inflammatory disease genetics

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https://www.readbyqxmd.com/read/28634323/intestinal-microbial-dysbiosis-aggravates-the-progression-of-alzheimer-s-disease-in-drosophila
#1
Shih-Cheng Wu, Zih-Syuan Cao, Kuo-Ming Chang, Jyh-Lyh Juang
Neuroinflammation caused by local deposits of Aβ42 in the brain is key for the pathogenesis and progression of Alzheimer's disease. However, inflammation in the brain is not always a response to local primary insults. Gut microbiota dysbiosis, which is recently emerging as a risk factor for psychiatric disorders, can also initiate a brain inflammatory response. It still remains unclear however, whether enteric dysbiosis also contributes to Alzheimer's disease. Here we show that in a Drosophila Alzheimer's disease model, enterobacteria infection exacerbated progression of Alzheimer's disease by promoting immune hemocyte recruitment to the brain, thereby provoking TNF-JNK mediated neurodegeneration...
June 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28633443/nod2-genetic-variants-predispose-one-of-two-familial-adenomatous-polyposis-siblings-to-pouchitis-through-microbiome-dysbiosis
#2
Kathleen M Schieffer, Justin R Wright, Leonard R Harris, Sue Deiling, Zhaohai Yang, Regina Lamendella, Gregory S Yochum, Walter A Koltun
Background and Aims: Individuals with familial adenomatous polyposis (FAP) may undergo a total proctocolectomy with ileal pouch-anal anastomosis (IPAA) to surgically treat their disease. Inflammation of the ileal pouch, termed pouchitis, is uncommon in FAP patients but prevalent in patients who received IPAA for ulcerative colitis, a type of inflammatory bowel disease (IBD). Methods and Results: We report on two FAP siblings, living in the same household, who underwent IPAA surgery within one week of each other...
June 19, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28632155/microbiota-inflammation-and-colorectal-cancer
#3
REVIEW
Cécily Lucas, Nicolas Barnich, Hang Thi Thu Nguyen
Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28631608/one-year-in-review-2017-pathogenesis-of-rheumatoid-arthritis
#4
Francesca Angelotti, Alice Parma, Giacomo Cafaro, Riccardo Capecchi, Alessia Alunno, Ilaria Puxeddu
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by both genetic and environmental factors. It has been postulated that a high-risk genetic background, in combination with epigenetic marks and environmental exposures, leads to a cascade of events inducing synovitis and consequent destructive arthritis. The clinical picture of joint involvement in RA is the result of chronic inflammation of the synovium, characterised by interactions of resident cells such as fibroblast-like synoviocytes (FLS) with cells of the innate (e...
May 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28629999/trimethylamine-n-oxide-prime-nlrp3-inflammasome-via-inhibiting-atg16l1-induced-autophagy-in-colonic-epithelial-cells
#5
Chaochi Yue, Xiangdong Yang, Jun Li, Xiaochao Chen, Xiangdong Zhao, Ye Chen, Yong Wen
Recently, the intricate relationship between Trimethylamine N-oxide (TMAO) and inflammatory bowel disease (IBD) is of growing interest. The NLRP3 inflammasome plays crucial roles in gut homeostasis and determining the severity of inflammation in IBD, however, the precise roles of the NLRP3 inflammasome in IBD are still debated. ATG16L1 mediates the cellular degradative process of autophagy and is considered a critical regulator of inflammation based on its genetic association with IBD. Whether TMAO prime NLRP3 inflammasome via ATG16L1-induced autophagy remains unclear...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28629387/an-updated-assessment-of-microglia-depletion-current-concepts-and-future-directions
#6
REVIEW
Jinming Han, Robert A Harris, Xing-Mei Zhang
Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris...
June 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28628665/a-chromosome-5q31-1-locus-associates-with-tuberculin-skin-test-reactivity-in-hiv-positive-individuals-from-tuberculosis-hyper-endemic-regions-in-east-africa
#7
Rafal S Sobota, Catherine M Stein, Nuri Kodaman, Isaac Maro, Wendy Wieland-Alter, Robert P Igo, Albert Magohe, LaShaunda L Malone, Keith Chervenak, Noemi B Hall, Mecky Matee, Harriet Mayanja-Kizza, Moses Joloba, Jason H Moore, William K Scott, Timothy Lahey, W Henry Boom, C Fordham von Reyn, Scott M Williams, Giorgio Sirugo
One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28626742/association-study-of-glutathione-s-transferases-gene-polymorphisms-gstm1-and-gstt1-with-ulcerative-colitis-and-crohn-s-disease-in-the-south-of-iran
#8
Maryam Moini, Mostafa Saadat, Hooshang Saadat, Atefeh Esmailnejad, Alireza Safarpour
BACKGROUND: Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory disorders of the gastrointestinal tract. A combination of environmental factors and interactions with a genetic predisposition are suggested to play an important role in the etiology and pathogenesis of the IBD. Glutathione S-transferases (GSTs) are multifunctional enzymes involved in the cellular oxidative stress handling. Possible associations between GSTs gene polymorphisms and susceptibility to UC and CD have been reported in different population...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28623538/clinically-promising-biomarkers-in-cystic-fibrosis-pulmonary-exacerbations
#9
REVIEW
L Keith Scott, Robert Toner
Cystic fibrosis is a complex genetic disease hallmarked by repetitive infectious exacerbations that leads to destruction of airway architecture, acute on chronic inflammatory changes, and deterioration in lung function. Predicting an exacerbation may help preempt some of these changes by the initiation of swift antibiotic and anti-inflammatory therapy. A search for biomarkers that could predict exacerbations or help guide duration of antibiotic therapy is being aggressively sought. In this review, we discuss the most recent and promising biomarkers that hopefully will assist in the future management of the CF patient...
June 16, 2017: Lung
https://www.readbyqxmd.com/read/28621249/tuberculosis-masked-by-immunodeficiency-a-review-of-two-cases-diagnosed-with-chronic-granulomatous-disease
#10
Hikmet Tekin Nacaroğlu, Semiha Bahçeci Erdem, Nesrin Gülez, Canan Şule Ünsal Karkıner, İlker Devrim, Ferah Genel, Mustafa Yavuz Köker, Demet Can
Chronic granulomatous disease (CGD) is a genetically heterogeneous primary immunodeficiency that is characterized by recurrent and life-threatening infections resulting from defects in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system and granuloma formation due to increased inflammatory response. The most commonly involved organs are the lungs, skin, lymph nodes, and liver due to infection. It may present with recurrent pneumonia, hilar lymphadenopathy, empyema, abscess, reticulonodular patterns, and granulomas due to lung involvement...
March 2017: Tüberküloz Ve Toraks
https://www.readbyqxmd.com/read/28620346/primary-progressive-multiple-sclerosis-putting-together-the-puzzle
#11
REVIEW
Ahmed Abdelhak, Martin S Weber, Hayrettin Tumani
The focus of multiple sclerosis research has recently turned to the relatively rare and clearly more challenging condition of primary progressive multiple sclerosis (PPMS). Many risk factors such as genetic susceptibility, age, and Epstein-Barr virus (EBV) infection may interdepend on various levels, causing a complex pathophysiological cascade. Variable pathological mechanisms drive disease progression, including inflammation-associated axonal loss, continuous activation of central nervous system resident cells, such as astrocytes and microglia as well as mitochondrial dysfunction and iron accumulation...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28619997/cardiotonic-steroids-stimulate-macrophage-inflammatory-responses-through-a-pathway-involving-cd36-tlr4-and-na-k-atpase
#12
Yiliang Chen, Wenxin Huang, Moua Yang, Gang Xin, Weiguo Cui, Zijian Xie, Roy L Silverstein
OBJECTIVE: Circulating levels of cardiotonic steroids (CTS) are elevated in various chronic inflammatory conditions, but the role of CTS in inflammation remains largely unknown. We have previously shown that the CTS ouabain stimulates proinflammatory responses in murine macrophages. In this study, we aim to explore the mechanism how CTS induce proinflammatory responses in primary murine and human macrophages. APPROACH AND RESULTS: Using both murine peritoneal macrophages and human monocyte-derived macrophages, we demonstrated that ouabain activated NF-κB, leading to proinflammatory cytokine (eg, MCP-1, tumor necrosis factor-α, interleukin-1β, and interleukin-6) production...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28619710/heme-oxygenase-1-production-by-intestinal-cx3cr1-macrophages-helps-to-resolve-inflammation-and-prevents-carcinogenesis
#13
Giulia Marelli, Marco Erreni, Achille Anselmo, Valentina Taverniti, Simone Guglielmetti, Alberto Mantovani, Paola Allavena
CX3CR1(+) macrophages in the intestinal lamina propria contribute to gut homeostasis through the immunomodulatory interleukin IL-10, but there is little knowledge on how these cells or the CX3CR1 receptor may affect colorectal carcinogenesis. In this study, we show that CX3CR1-deficient mice fail to resolve gut inflammation despite high production of IL-10 and have increased colitis and adenomatous polyps in chemical and genetic models of colon carcinogenesis. Mechanistically, CX3CL1-mediated engagement of the CX3CR1 receptor induced upregulation of hemoxygenase-1 (HMOX-1), an antioxidant and anti-inflammatory enzyme...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28619429/vitamin-d-and-multiple-sclerosis-an-update
#14
REVIEW
Charles Pierrot-Deseilligny, Jean-Claude Souberbielle
The most recent findings linking exposure to sun and vitamin D insufficiency to multiple sclerosis (MS) are reviewed. Due to insufficient sunshine and changing lifestyles, hypovitaminosis D is widespread in temperate countries. Numerous epidemiological studies have strongly suggested that sunshine and vitamin D insufficiency contributes to MS risk in these countries. Moreover, several large genetic studies in MS patients have recently stated unequivocally that diverse abnormalities involving vitamin D metabolism are related to the risk of the disease...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28616751/roles-of-amino-acids-in-preventing-and-treating-intestinal-diseases-recent-studies-with-pig-models
#15
REVIEW
Yulan Liu, Xiuying Wang, Yongqing Hou, Yulong Yin, Yinsheng Qiu, Guoyao Wu, Chien-An Andy Hu
Animal models are needed to study and understand a human complex disease. Because of their similarities in anatomy, structure, physiology, and pathophysiology, the pig has proven its usefulness in studying human gastrointestinal diseases, such as inflammatory bowel disease, ischemia/reperfusion injury, diarrhea, and cancer. To understand the pathogenesis of these diseases, a number of experimental models generated in pigs are available, for example, through surgical manipulation, chemical induction, microbial infection, and genetic engineering...
June 14, 2017: Amino Acids
https://www.readbyqxmd.com/read/28615730/pain-in-ankylosing-spondylitis-a-neuro-immune-collaboration
#16
REVIEW
Katayoon Bidad, Eric Gracey, Kasey S Hemington, Josiane C S Mapplebeck, Karen D Davis, Robert D Inman
Clinicians have commonly differentiated chronic back pain into two broad subsets: namely, non-inflammatory (or mechanical) back pain and inflammatory back pain. As the terminology suggests, the latter category, in which ankylosing spondylitis (AS) is prominent, presupposes a close link between pain and inflammation. Advances in research into the genetics and immunology of AS have improved our understanding of the inflammatory processes involved in this disease, and have led to the development of potent anti-inflammatory biologic therapeutic agents...
June 15, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28615046/the-association-of-insertions-deletions-indels-and-variable-number-tandem-repeats-vntrs-with-obesity-and-its-related-traits-and-complications
#17
REVIEW
Yee-How Say
BACKGROUND: Despite the fact that insertions/deletions (INDELs) are the second most common type of genetic variations and variable number tandem repeats (VNTRs) represent a large portion of the human genome, they have received far less attention than single nucleotide polymorphisms (SNPs) and larger forms of structural variation like copy number variations (CNVs), especially in genome-wide association studies (GWAS) of complex diseases like polygenic obesity. This is exemplified by the vast amount of review papers on the role of SNPs and CNVs in obesity, its related traits (like anthropometric measurements, biochemical variables, and eating behavior), and its related complications (like hypertension, hypertriglyceridemia, hypercholesterolemia, and insulin resistance-collectively known as metabolic syndrome)...
June 14, 2017: Journal of Physiological Anthropology
https://www.readbyqxmd.com/read/28612750/genetic-and-epigenetic-profile-of-patients-with-alcoholic-liver-disease
#18
Luigi Boccuto, Ludovico Abenavoli
Alcoholic liver disease (ALD) is a definition encompassing a spectrum of disorders ranging from simple steatosis to cirrhosis and hepatocellular carcinoma. Excessive alcohol consumption triggers a series of metabolic reactions that affect the liver by inducing lipogenesis, increasing oxidative stress, and causing abnormal inflammatory responses. The metabolic pathways regulating lipids, reactive oxygen species (ROS), and immune system are closely related and in some cases cross-regulate each other. Therefore, it must be taken into account that major genetic and epigenetic abnormalities affecting enzymes involved in one of such pathways can play a pivotal role in ALD pathogenesis...
August 1, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28612290/deficiency-of-tyrobp-an-adapter-protein-for-trem2-and-cr3-receptors-is-neuroprotective-in-a-mouse-model-of-early-alzheimer-s-pathology
#19
Jean-Vianney Haure-Mirande, Mickael Audrain, Tomas Fanutza, Soong Ho Kim, William L Klein, Charles Glabe, Ben Readhead, Joel T Dudley, Robert D Blitzer, Minghui Wang, Bin Zhang, Eric E Schadt, Sam Gandy, Michelle E Ehrlich
Conventional genetic approaches and computational strategies have converged on immune-inflammatory pathways as key events in the pathogenesis of late onset sporadic Alzheimer's disease (LOAD). Mutations and/or differential expression of microglial specific receptors such as TREM2, CD33, and CR3 have been associated with strong increased risk for developing Alzheimer's disease (AD). DAP12 (DNAX-activating protein 12)/TYROBP, a molecule localized to microglia, is a direct partner/adapter for TREM2, CD33, and CR3...
June 13, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28611935/gastrointestinal-amyloidosis-review-of-the-literature
#20
REVIEW
Kyle Rowe, Jon Pankow, Fredy Nehme, William Salyers
Gastrointestinal amyloidosis (GIA), a protein deposition disorder, represents a complex common pathway that encompasses multiple etiologies and presentations. It represents a significant diagnostic and treatment challenge. The disease results from the deposition of insoluble extracellular protein fragments that have been rendered resistant to digestion. GIA can be acquired or genetic, and most commonly results from chronic inflammatory disorders (AA amyloidosis), hematologic malignancy (AL amyloidosis), and end-stage renal disease (Beta-2 amyloidosis)...
May 8, 2017: Curēus
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