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Gene expression profile of human plaque

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https://www.readbyqxmd.com/read/29196460/microglia-in-alzheimer-s-disease
#1
REVIEW
David V Hansen, Jesse E Hanson, Morgan Sheng
Proliferation and activation of microglia in the brain, concentrated around amyloid plaques, is a prominent feature of Alzheimer's disease (AD). Human genetics data point to a key role for microglia in the pathogenesis of AD. The majority of risk genes for AD are highly expressed (and many are selectively expressed) by microglia in the brain. There is mounting evidence that microglia protect against the incidence of AD, as impaired microglial activities and altered microglial responses to β-amyloid are associated with increased AD risk...
December 1, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29190775/transcriptome-profiling-analysis-of-senescent-gingival-fibroblasts-in-response-to-fusobacterium-nucleatum-infection
#2
Sun-Hee Ahn, Sung-Min Chun, Chungoo Park, Jong-Hee Lee, Seok-Woo Lee, Tae-Hoon Lee
Periodontal disease is caused by dental plaque biofilms. Fusobacterium nucleatum is an important periodontal pathogen involved in the development of bacterial complexity in dental plaque biofilms. Human gingival fibroblasts (GFs) act as the first line of defense against oral microorganisms and locally orchestrate immune responses by triggering the production of reactive oxygen species and pro-inflammatory cytokines (IL-6 and IL-8). The frequency and severity of periodontal diseases is known to increase in elderly subjects...
2017: PloS One
https://www.readbyqxmd.com/read/29038051/integrated-approach-reveals-diet-apoe-genotype-and-sex-affect-immune-response-in-app-mice
#3
Kyong Nyon Nam, Cody M Wolfe, Nicholas F Fitz, Florent Letronne, Emilie L Castranio, Anais Mounier, Jonathan Schug, Iliya Lefterov, Radosveta Koldamova
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is influenced by genetic and environmental risk factors, such as inheritance of ε4 allele of APOE (APOE4), sex and diet. Here, we examined the effect of high fat diet (HFD) on amyloid pathology and expression profile in brains of AD model mice expressing human APOE isoforms (APP/E3 and APP/E4 mice). APP/E3 and APP/E4 mice were fed HFD or Normal diet for 3months. We found that HFD significantly increased amyloid plaques in male and female APP/E4, but not in APP/E3 mice...
October 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29021166/an-analysis-of-il-36-signature-genes-and-individuals-with-il1rl2-knockout-mutations-validates-il-36-as-a-psoriasis-therapeutic-target
#4
Satveer K Mahil, Marika Catapano, Paola Di Meglio, Nick Dand, Helena Ahlfors, Ian M Carr, Catherine H Smith, Richard C Trembath, Mark Peakman, John Wright, Francesca D Ciccarelli, Jonathan N Barker, Francesca Capon
Interleukin (IL)-36α, IL-36β, and IL-36γ are innate mediators of acute epithelial inflammation. We sought to demonstrate that these cytokines are also required for the pathogenesis of plaque psoriasis, a common and chronic skin disorder, caused by abnormal T helper 17 (TH17) cell activation. To investigate this possibility, we first defined the genes that are induced by IL-36 cytokines in primary human keratinocytes. This enabled us to demonstrate a significant IL-36 signature among the transcripts that are up-regulated in plaque psoriasis and the susceptibility loci associated with the disease in genome-wide studies...
October 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28899419/increased-plasma-lipid-levels-exacerbate-muscle-pathology-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy
#5
Nadia Milad, Zoe White, Arash Y Tehrani, Stephanie Sellers, Fabio M V Rossi, Pascal Bernatchez
BACKGROUND: Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin expression and leads to severe ambulatory and cardiac function decline. However, the dystrophin-deficient mdx murine model of DMD only develops a very mild form of the disease. Our group and others have shown vascular abnormalities in animal models of MD, a likely consequence of the fact that blood vessels express the same dystrophin-associated glycoprotein complex (DGC) proteins as skeletal muscles. METHODS: To test the blood vessel contribution to muscle damage in DMD, mdx (4cv) mice were given elevated lipid levels via apolipoprotein E (ApoE) gene knockout combined with normal chow or lipid-rich Western diets...
September 12, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28668092/dissecting-the-role-of-non-coding-rnas-in-the-accumulation-of-amyloid-and-tau-neuropathologies-in-alzheimer-s-disease
#6
Ellis Patrick, Sathyapriya Rajagopal, Hon-Kit Andus Wong, Cristin McCabe, Jishu Xu, Anna Tang, Selina H Imboywa, Julie A Schneider, Nathalie Pochet, Anna M Krichevsky, Lori B Chibnik, David A Bennett, Philip L De Jager
BACKGROUND: Given multiple studies of brain microRNA (miRNA) in relation to Alzheimer's disease (AD) with few consistent results and the heterogeneity of this disease, the objective of this study was to explore their mechanism by evaluating their relation to different elements of Alzheimer's disease pathology, confounding factors and mRNA expression data from the same subjects in the same brain region. METHODS: We report analyses of expression profiling of miRNA (n = 700 subjects) and lincRNA (n = 540 subjects) from the dorsolateral prefrontal cortex of individuals participating in two longitudinal cohort studies of aging...
July 1, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28434692/immune-hyperreactivity-of-a%C3%AE-plaque-associated-microglia-in-alzheimer-s-disease
#7
Zhuoran Yin, Divya Raj, Nasrin Saiepour, Debby Van Dam, Nieske Brouwer, Inge R Holtman, Bart J L Eggen, Thomas Möller, Joseph A Tamm, Aicha Abdourahman, Elly M Hol, Willem Kamphuis, Thomas A Bayer, Peter P De Deyn, Erik Boddeke
Alzheimer's disease (AD) is strongly associated with microglia-induced neuroinflammation. Particularly, Aβ plaque-associated microglia take on an "activated" morphology. However, the function and phenotype of these Aβ plaque-associated microglia are not well understood. We show hyperreactivity of Aβ plaque-associated microglia upon systemic inflammation in transgenic AD mouse models (i.e., 5XFAD and APP23). Gene expression profiling of Aβ plaque-associated microglia (major histocompatibility complex II(+) microglia) isolated from 5XFAD mice revealed a proinflammatory phenotype...
March 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28319050/extracellular-matrix-proteomics-identifies-molecular-signature-of-symptomatic-carotid-plaques
#8
Sarah R Langley, Karin Willeit, Athanasios Didangelos, Ljubica Perisic Matic, Philipp Skroblin, Javier Barallobre-Barreiro, Mariette Lengquist, Gregor Rungger, Alexander Kapustin, Ludmilla Kedenko, Chris Molenaar, Ruifang Lu, Temo Barwari, Gonca Suna, Xiaoke Yin, Bernhard Iglseder, Bernhard Paulweber, Peter Willeit, Joseph Shalhoub, Gerard Pasterkamp, Alun H Davies, Claudia Monaco, Ulf Hedin, Catherine M Shanahan, Johann Willeit, Stefan Kiechl, Manuel Mayr
BACKGROUND: The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the "vulnerable plaque," necessitating an improved approach for predicting onset of symptoms. METHODS: We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28224128/upregulation-of-th-il-17-pathway-related-genes-in-human-coronary-endothelial-cells-stimulated-with-serum-of-patients-with-acute-coronary-syndromes
#9
Giovanni Cimmino, Loreta Pia Ciuffreda, Giovanni Ciccarelli, Paolo Calabrò, Fiorella Angelica Valeria Ferraiolo, Alessia Rivellino, Raffaele De Palma, Paolo Golino, Francesco Rossi, Plinio Cirillo, Liberato Berrino
BACKGROUND: Inflammation plays an essential role in the development and complications of atherosclerosis plaques, including acute coronary syndromes (ACS). Indeed, previous reports have shown that within the coronary circulation of ACS patients, several soluble mediators are released. Moreover, it has been demonstrated that endothelial dysfunction might play an important role in atherosclerosis as well as ACS pathophysiology. However, the mechanisms by which these soluble mediators might affect endothelial functions are still largely unknown...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28137856/targeting-ire1-with-small-molecules-counteracts-progression-of-atherosclerosis
#10
Ozlem Tufanli, Pelin Telkoparan Akillilar, Diego Acosta-Alvear, Begum Kocaturk, Umut Inci Onat, Syed Muhammad Hamid, Ismail Çimen, Peter Walter, Christian Weber, Ebru Erbay
Metaflammation, an atypical, metabolically induced, chronic low-grade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation. The most conserved ER-resident UPR regulator, the kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), is activated in lipid-laden macrophages that infiltrate the atherosclerotic lesions...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28089213/a-genome-wide-profiling-of-brain-dna-hydroxymethylation-in-alzheimer-s-disease
#11
Jinying Zhao, Yun Zhu, Jingyun Yang, Lin Li, Hao Wu, Philip L De Jager, Peng Jin, David A Bennett
INTRODUCTION: DNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5-hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life experiences. However, little is known about its genome-wide patterns and potential role in AD. METHODS: Using a genome-wide capture followed by high-throughput sequencing, we studied the genome-wide distribution of 5-hydroxymethylcytosine at specific genomic loci in human AD brain and identified differentially hydroxymethylated regions (DhMRs) associated with AD pathology...
January 6, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27818938/modulation-of-ambient-temperature-promotes-inflammation-and-initiates-atherosclerosis-in-wild-type-c57bl-6-mice
#12
Daniel A Giles, Bhama Ramkhelawon, Elizabeth M Donelan, Traci E Stankiewicz, Susan B Hutchison, Rajib Mukherjee, Monica Cappelletti, Rebekah Karns, Christopher L Karp, Kathryn J Moore, Senad Divanovic
OBJECTIVES: Obesity and obesity-associated inflammation is central to a variety of end-organ sequelae including atherosclerosis, a leading cause of death worldwide. Although mouse models have provided important insights into the immunopathogenesis of various diseases, modeling atherosclerosis in mice has proven difficult. Specifically, wild-type (WT) mice are resistant to developing atherosclerosis, while commonly used genetically modified mouse models of atherosclerosis are poor mimics of human disease...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27727291/early-transcriptomic-response-to-ldl-and-oxldl-in-human-vascular-smooth-muscle-cells
#13
Salvador Damián-Zamacona, Paola Toledo-Ibelles, Mabel Z Ibarra-Abundis, Laura Uribe-Figueroa, Enrique Hernández-Lemus, Karla Paola Macedo-Alcibia, Blanca Delgado-Coello, Jaime Mas-Oliva, Juan Pablo Reyes-Grajeda
BACKGROUND: Although nowadays it is well known that the human transcriptome can importantly vary according to external or environmental condition, the reflection of this concept when studying oxidative stress and its direct relationship with gene expression profiling during the process of atherogenesis has not been thoroughly achieved. OBJECTIVE: The ability to analyze genome-wide gene expression through transcriptomics has shown that the genome responds dynamically to diverse stimuli...
2016: PloS One
https://www.readbyqxmd.com/read/27707922/syncytial-mutations-do-not-impair-the-specificity-of-entry-and-spread-of-a-glycoprotein-d-receptor-retargeted-herpes-simplex-virus
#14
Yu Okubo, Hiroaki Uchida, Aika Wakata, Takuma Suzuki, Tomoko Shibata, Hitomi Ikeda, Miki Yamaguchi, Justus B Cohen, Joseph C Glorioso, Mitsuo Tagaya, Hirofumi Hamada, Hideaki Tahara
Membrane fusion, which is the key process for both initial cell entry and subsequent lateral spread of herpes simplex virus (HSV), requires the four envelope glycoproteins gB, gD, gH, and gL. Syncytial mutations, predominantly mapped to the gB and gK genes, confer hyperfusogenicity on HSV and cause multinucleated giant cells, termed syncytia. Here we asked whether interaction of gD with a cognate entry receptor remains indispensable for initiating membrane fusion of syncytial strains. To address this question, we took advantage of mutant viruses whose viral entry into cells relies on the uniquely specific interaction of an engineered gD with epidermal growth factor receptor (EGFR)...
December 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27513102/tissue-engineered-human-psoriatic-skin-supplemented-with-cytokines-as-an-in%C3%A2-vitro-model-to-study-plaque-psoriasis
#15
Claudia Pouliot-Bérubé, Karine Zaniolo, Sylvain L Guérin, Roxane Pouliot
AIM: Psoriasis is a chronic inflammatory skin disease. To study its complex etiology, a psoriatic skin substitute model supplemented with a cytokine cocktail has been used. MATERIALS & METHODS: Reconstructed psoriatic skin substitutes were supplemented with a cocktail of four cytokines: TNF-α, IL-1α, IL-6 and IL-17A, to monitor their impact on gene expression by DNA microarray. RESULTS: Gene profiling analyses identified several deregulated genes reported as being also deregulated in psoriasis skin in vivo (S100A12, IL-8, DEFB4A and KYNU)...
September 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27400380/metagenome-and-metatranscriptome-analyses-using-protein-family-profiles
#16
Cuncong Zhong, Anna Edlund, Youngik Yang, Jeffrey S McLean, Shibu Yooseph
Analyses of metagenome data (MG) and metatranscriptome data (MT) are often challenged by a paucity of complete reference genome sequences and the uneven/low sequencing depth of the constituent organisms in the microbial community, which respectively limit the power of reference-based alignment and de novo sequence assembly. These limitations make accurate protein family classification and abundance estimation challenging, which in turn hamper downstream analyses such as abundance profiling of metabolic pathways, identification of differentially encoded/expressed genes, and de novo reconstruction of complete gene and protein sequences from the protein family of interest...
July 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27350674/improving-lipoprotein-profiles-by-liver-directed-gene-transfer-of-low-density-lipoprotein-receptor-gene-in-hypercholesterolaemia-mice
#17
Hailong Ou, Qinghai Zhang, Jia Zeng
The defect of low density lipoprotein receptor disturbs cholesterol metabolism and causes familial hypercholesterolaemia (FH). In this study, we directly delivered exogenous Ldlr gene into the liver of FH model mice (Ldlr(-/-)) by lentiviral gene transfer system. The results showed that the Ldlr gene controlled by hepatocyte-specific human thyroxine-binding globulin (TBG) promoter successfully and exclusively expressed in livers.We found that, although, the content of high density lipoprotein in serum was not significantly affected by the Ldlr gene expression, the serum low density lipoprotein level was reduced by 46%, associated with a 30% and 28% decrease in triglyceride and total cholesterol, respectively, compared to uninjected Ldlr(-/-) mice...
June 2016: Journal of Genetics
https://www.readbyqxmd.com/read/27180200/amendment-of-the-cytokine-profile-in-macrophages-subsequent-to-their-interaction-with-smooth-muscle-cells-differential-modulation-by-fractalkine-and-resistin
#18
Monica Madalina Tucureanu, Elena Butoi, Ana-Maria Gan, Daniela Stan, Cristina Ana Constantinescu, Manuela Calin, Maya Simionescu, Ileana Manduteanu
In atherosclerotic plaques, macrophages (MAC) and smooth muscle cells (SMC) frequently reside in close proximity and resistin (Rs) and fractalkine (Fk) are present at increased levels, resistin being associated with CD68 macrophages and fractalkine predominantly associated with intimal SMC; however, their role in this location is not clear, yet. The objective of this study was to determine whether the cross-talk between MAC-SMC induces changes in MAC cytokine phenotype and if Fk and Rs have a role in the process...
July 2016: Cytokine
https://www.readbyqxmd.com/read/27124409/porphyromonas-gingivalis-differentially-modulates-cell-death-profile-in-ox-ldl-and-tnf-%C3%AE-pre-treated-endothelial-cells
#19
Isaac Maximiliano Bugueno, Yacine Khelif, Narendra Seelam, David-Nicolas Morand, Henri Tenenbaum, Jean-Luc Davideau, Olivier Huck
OBJECTIVE: Clinical studies demonstrated a potential link between atherosclerosis and periodontitis. Porphyromonas gingivalis (Pg), one of the main periodontal pathogen, has been associated to atheromatous plaque worsening. However, synergism between infection and other endothelial stressors such as oxidized-LDL or TNF-α especially on endothelial cell (EC) death has not been investigated. This study aims to assess the role of Pg on EC death in an inflammatory context and to determine potential molecular pathways involved...
2016: PloS One
https://www.readbyqxmd.com/read/27058954/amyloid-beta-mediated-hypomethylation-of-heme-oxygenase-1-correlates-with-cognitive-impairment-in-alzheimer-s-disease
#20
Hye Youn Sung, Byung-Ok Choi, Jee Hyang Jeong, Kyoung Ae Kong, Jinha Hwang, Jung-Hyuck Ahn
To identify epigenetically regulated genes involved in the pathogenesis of Alzheimer's disease (AD) we analyzed global mRNA expression and methylation profiles in amyloid precursor protein (APP)-Swedish mutant-expressing AD model cells, H4-sw and selected heme oxygenase-1 (HMOX1), which is associated with pathological features of AD such as neurofibrillary tangles and senile plaques. We examined the epigenetic regulatory mechanism of HMOX1 and its application as a diagnostic and prognostic biomarker for AD...
2016: PloS One
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