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https://www.readbyqxmd.com/read/28185567/from-comorbidities-of-chronic-obstructive-pulmonary-disease-to-identification-of-shared-molecular-mechanisms-by-data-integration
#1
David Gomez-Cabrero, Jörg Menche, Claudia Vargas, Isaac Cano, Dieter Maier, Albert-László Barabási, Jesper Tegnér, Josep Roca
BACKGROUND: Deep mining of healthcare data has provided maps of comorbidity relationships between diseases. In parallel, integrative multi-omics investigations have generated high-resolution molecular maps of putative relevance for understanding disease initiation and progression. Yet, it is unclear how to advance an observation of comorbidity relations (one disease to others) to a molecular understanding of the driver processes and associated biomarkers. RESULTS: Since Chronic Obstructive Pulmonary disease (COPD) has emerged as a central hub in temporal comorbidity networks, we developed a systematic integrative data-driven framework to identify shared disease-associated genes and pathways, as a proxy for the underlying generative mechanisms inducing comorbidity...
November 22, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28182609/genetic-polymorphisms-associated-with-liver-disease-progression-in-hiv-hcv-coinfected-patients
#2
REVIEW
Luz M Medrano, María A Jiménez-Sousa, Amanda Fernández-Rodríguez, Salvador Resino
The pathogenic mechanisms of the accelerated progression of liver injury in HIV/HCV coinfection are incompletely understood. The progression of liver disease is variable between individuals having similar risk factors, suggesting that genetic background is an important contributor. The aim of this review is to give a summary of all single nucleotide polymorphisms associated with the severity of liver disease in patients coinfected with HIV and HCV reported in the literature. Therefore, a systematic search for articles published was made, 17 of which were selected for this review...
January 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28164472/the-il15-96522-a-t-functional-polymorphism-is-related-to-the-differentiation-of-th17-cells-and-the-severity-of-hashimoto-s-disease
#3
Y Arakawa, M Watanabe, K Takemura, N Inoue, Y Hidaka, Y Iwatani
To clarify the association between the genetic producibility of IL-15, a pro-inflammatory cytokine, and the pathogenesis of autoimmune thyroid diseases (AITDs), we genotyped +96522 A>T and +82889 A>G polymorphisms in the IL15 gene using 127 patients with Hashimoto's disease (HD), including 55 patients with severe HD and 48 patients with mild HD; 130 patients with Graves' disease (GD), including 52 patients with intractable GD and 44 patients with GD in remission; and 79 healthy volunteers. Both the IL15 +96522 A allele and AA genotype were more frequent in patients with severe HD than in those with mild HD...
April 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28115367/lgl-leukemia-from-pathogenesis-to-treatment
#4
REVIEW
Thierry Lamy, Aline Moignet, Thomas P Loughran
Large granular lymphocyte (LGL) leukemia has been recognized by the World Health Organization classifications amongst mature T-cell and natural killer (NK) cell neoplasms. There are 3 categories: chronic T-cell leukemia and NK-cell lymphocytosis, which are similarly indolent diseases characterized by cytopenias and autoimmune conditions as opposed to aggressive NK-cell LGL leukemia. Clonal LGL expansion arise from chronic antigenic stimulation, which promotes dysregulation of apoptosis, mainly due to constitutive activation of survival pathways including Jak/Stat, MapK, phosphatidylinositol 3-kinase-Akt, Ras-Raf-1, MEK1/extracellular signal-regulated kinase, sphingolipid, and nuclear factor-κB...
March 2, 2017: Blood
https://www.readbyqxmd.com/read/28099143/desirable-cytolytic-immune-effector-cell-recruitment-by-interleukin-15-dendritic-cells
#5
Heleen H Van Acker, Ottavio Beretta, Sébastien Anguille, Lien De Caluwé, Angela Papagna, Johan M Van den Bergh, Yannick Willemen, Herman Goossens, Zwi N Berneman, Viggo F Van Tendeloo, Evelien L Smits, Maria Foti, Eva Lion
Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/27999750/reprogramming-the-lung-microenvironment-by-inhaled-immunotherapy-fosters-immune-destruction-of-tumor
#6
Valentino Le Noci, Michele Sommariva, Monica Tortoreto, Nadia Zaffaroni, Manuela Campiglio, Elda Tagliabue, Andrea Balsari, Lucia Sfondrini
Due to their constant exposure to inhaled antigens, lungs represent a particularly immunosuppressive environment that limits excessive immune responses; however, cancer cells can exploit this unique environment for their growth. We previously described the ability of aerosolized CpG-ODN combined with Poly(I:C) (TLR9 and TLR3 agonists, respectively) to promote antitumor immunity in a B16 melanoma lung metastasis model. Here, we explored the possibility of improving the therapeutic efficacy of TLR9/TLR3 agonist combinations by including in the inhalant either an antibody directed to both Ly6G and Ly6C markers to locally deplete myeloid-derived suppressive cells (MDSCs) or IFNα to directly activate the natural killer (NK) and macrophage innate immune cells in the lung...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27997584/prediction-of-possible-biomarkers-and-novel-pathways-conferring-risk-to-post-traumatic-stress-disorder
#7
Kumaraswamy Naidu Chitrala, Prakash Nagarkatti, Mitzi Nagarkatti
Post-traumatic stress disorder is one of the common mental ailments that is triggered by exposure to traumatic events. Till date, the molecular factors conferring risk to the development of PTSD is not well understood. In this study, we have conducted a meta-analysis followed by hierarchical clustering and functional enrichment, to uncover the potential molecular networks and critical genes which play an important role in PTSD. Two datasets of expression profiles from Peripheral Blood Mononuclear Cells from 62 control samples and 63 PTSD samples were included in our study...
2016: PloS One
https://www.readbyqxmd.com/read/27992487/changes-in-host-cytokine-patterns-of-tb-patients-with-different-bacterial-loads-detected-using-16s-rrna-analysis
#8
Rhiannon Heslop, Adama L Bojang, Sheikh Jarju, Joseph Mendy, Sarah Mulwa, Ousman Secka, Francis S Mendy, Olumuyiwa Owolabi, Beate Kampmann, Jayne S Sutherland
BACKGROUND: Tuberculosis (TB) has overtaken HIV as the biggest infectious disease killer, with the majority of deaths occurring in sub-Saharan Africa. However it is unknown how differences in bacterial load alter host immune profiles in the sputum and blood of TB patients. METHODS: 16S ribosomal RNA analysis was used to determine bacterial load in sputum samples obtained from 173 patients with active TB (57 pre-treatment and 116 post-treatment). Host analyte concentrations in sputum and Mycobacterium tuberculosis (Mtb) antigen stimulated whole blood assay supernatants were analysed using multiplex cytokine arrays...
2016: PloS One
https://www.readbyqxmd.com/read/27923824/human-dendritic-cells-mitigate-nk-cell-dysfunction-mediated-by-nonselective-jak1-2-blockade
#9
Shane A Curran, Justin A Shyer, Erin T St Angelo, Lillian R Talbot, Sneh Sharma, David J Chung, Glenn Heller, Katharine C Hsu, Brian C Betts, James W Young
Janus kinase (JAK) inhibitors have achieved positive responses in myeloproliferative neoplasms, but at the expense of decreased natural killer (NK) cell numbers and compromised function. Selective JAK2 inhibition may also have a role in preventing and treating graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Although JAK inhibitors can impair monocyte-derived dendritic cell (moDC) activation and function and suppress effector T-cell responses, the effects on NK cells and the relevant mechanisms remain undefined...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27677155/changes-in-expression-of-genes-involved-in-antitumor-immunity-in-mice-vaccinated-with-tumor-vaccine-composed-of-irradiated-syngeneic-tumor-cells-and-cpg-oligodeoxynucleotides
#10
Petra Cerkovnik, Barbara Jezeršek Novaković, Vida Stegel, Srdjan Novaković
In our previous studies, it has been demonstrated that in more than 80% of mice long-lasting antitumor immunity has been established following intraperitoneal (i.p.) vaccination with tumor vaccine composed of irradiated syngeneic tumor cells and CpG ODNs class C. The aim of this study was, therefore, to investigate molecular mechanisms through which this vaccine triggers the immunity and to define genes particularly involved in this process. Changes in gene expression were followed in mononuclear cells isolated from peritoneal lavages, spleens and bone marrow samples...
November 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27630154/accession-of-tumor-heterogeneity-by-multiplex-transcriptome-profiling-of-single-circulating-tumor-cells
#11
Tobias M Gorges, Andra Kuske, Katharina Röck, Oliver Mauermann, Volkmar Müller, Sven Peine, Karl Verpoort, Vendula Novosadova, Mikael Kubista, Sabine Riethdorf, Klaus Pantel
BACKGROUND: Transcriptome analysis of circulating tumor cells (CTCs) holds great promise to unravel the biology of cancer cell dissemination and identify expressed genes and signaling pathways relevant to therapeutic interventions. METHODS: CTCs were enriched based on their EpCAM expression (CellSearch(®)) or by size and deformability (Parsortix(TM)), identified by EpCAM and/or pan-keratin-specific antibodies, and isolated for single cell multiplex RNA profiling...
November 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/27602597/tributyltin-exposure-alters-cytokine-levels-in-mouse-serum
#12
Shanieek Lawrence, Samuel T Pellom, Anil Shanker, Margaret M Whalen
Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo...
November 2016: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/27538697/propionibacterium-acnes-overabundance-and-natural-killer-group-2-member-d-system-activation-in-corpus-dominant-lymphocytic-gastritis
#13
Ana Montalban-Arques, Philipp Wurm, Slave Trajanoski, Silvia Schauer, Sabine Kienesberger, Bettina Halwachs, Christoph Högenauer, Cord Langner, Gregor Gorkiewicz
Corpus-dominant lymphocytic gastritis (LyG) is characterized by CD8(+) T-cell infiltration of the stomach epithelium by a so far uncharacterized mechanism. Although Helicobacter pylori is typically undetectable in LyG, patients respond to H. pylori antibiotic eradication therapy, suggesting a non-H. pylori microbial trigger for the disease. Comparative microbiota analysis of specimens from LyG, H. pylori gastritis and healthy controls precluded involvement of H. pylori in LyG but identified Propionibacterium acnes as a possible disease trigger...
December 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27512375/doxorubicin-induces-inflammatory-modulation-and-metabolic-dysregulation-in-diabetic-skeletal-muscle
#14
Rashmi Supriya, Bjorn T Tam, Xiao M Pei, Christopher W Lai, Lawrence W Chan, Benjamin Y Yung, Parco M Siu
Anti-cancer agent doxorubicin (DOX) has been demonstrated to worsen insulin signaling, engender muscle atrophy, trigger pro-inflammation, and induce a shift to anaerobic glycolytic metabolism in skeletal muscle. The myotoxicity of DOX in diabetic skeletal muscle remains largely unclear. This study examined the effects of DOX on insulin signaling, muscle atrophy, pro-/anti-inflammatory microenvironment, and glycolysis metabolic regulation in skeletal muscle of db/db diabetic and db/+ non-diabetic mice. Non-diabetic db/+ mice and diabetic db/db mice were randomly assigned to the following groups: db/+CON, db/+DOX, db/dbCON, and db/dbDOX...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27502276/the-effect-of-cellular-stress-on-t-and-b-cell-memory-pathways-in-immunized-and-unimmunized-balb-c-mice
#15
Yufei Wang, Durdana Rahman, Mukesh Mistry, Thomas Lehner
Immunological memory is a fundamental function of vaccination. The antigenic breakdown products of the vaccine may not persist, and undefined tonic stimulation has been proposed to maintain the specific memory. We have suggested that cellular stress agents to which the immune cells are constantly exposed may be responsible for tonic stimulation. Here we have studied four stress agents: sodium arsenite, an oxidative agent; Gramicidin, eliciting K(+) efflux and calcium influx; dithiocarbamate, a metal ionophore; and aluminum hydroxide (alum), an immunological adjuvant...
September 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27485135/molecular-programming-of-tumor-infiltrating-cd8-t-cells-and-il15-resistance
#16
Andrew L Doedens, Mark P Rubinstein, Emilie T Gross, J Adam Best, David H Craig, Megan K Baker, David J Cole, Jack D Bui, Ananda W Goldrath
Despite clinical potential and recent advances, durable immunotherapeutic ablation of solid tumors is not routinely achieved. IL15 expands natural killer cell (NK), natural killer T cell (NKT) and CD8(+) T-cell numbers and engages the cytotoxic program, and thus is under evaluation for potentiation of cancer immunotherapy. We found that short-term therapy with IL15 bound to soluble IL15 receptor α-Fc (IL15cx; a form of IL15 with increased half-life and activity) was ineffective in the treatment of autochthonous PyMT murine mammary tumors, despite abundant CD8(+) T-cell infiltration...
September 2, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27472286/ccl2-ccl5-il4-and-il15-gene-polymorphisms-in-women-with-gestational-diabetes-mellitus
#17
Joanna Teler, Maciej Tarnowski, Krzysztof Safranow, Agnieszka Maciejewska, Marek Sawczuk, Violetta Dziedziejko, Sylwia Sluczanowska-Glabowska, Andrzej Pawlik
Gestational diabetes mellitus (GDM) is a glucose intolerance that occurs during pregnancy. Several studies suggest that inflammation contributes to pregnancy-induced insulin resistance and the development of glucose intolerance. The aim of this study is to examine the association between the CCL2, CCL5, IL4 and IL15 gene polymorphisms and the development of GDM. This study included 411 pregnant women who underwent a 75 g oral glucose tolerance test at 24-28 weeks of gestation. Participants were categorised into 2 groups according to results of the oral glucose tolerance test (OGTT)...
January 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27453994/altered-myokine-secretion-is-an-intrinsic-property-of-skeletal-muscle-in-type-2-diabetes
#18
Theodore P Ciaraldi, Alexander J Ryan, Sunder R Mudaliar, Robert R Henry
Skeletal muscle secretes factors, termed myokines. We employed differentiated human skeletal muscle cells (hSMC) cultured from Type 2 diabetic (T2D) and non-diabetic (ND) subjects to investigate the impact of T2D on myokine secretion. Following 24 hours of culture concentrations of selected myokines were determined to range over 4 orders of magnitude. T2D hSMC released increased amounts of IL6, IL8, IL15, TNFa, Growth Related Oncogene (GRO)a, monocyte chemotactic protein (MCP)-1, and follistatin compared to ND myotubes...
2016: PloS One
https://www.readbyqxmd.com/read/27445342/pilot-study-of-small-bowel-mucosal-gene-expression-in-patients-with-irritable-bowel-syndrome-with-diarrhea
#19
Michael Camilleri, Paula Carlson, Nelson Valentin, Andres Acosta, Jessica O'Neill, Deborah Eckert, Roy Dyer, Jie Na, Eric W Klee, Joseph A Murray
Prior studies in with irritable bowel syndrome with diarrhea (IBS-D) patients showed immune activation, secretion, and barrier dysfunction in jejunal or colorectal mucosa. We measured mRNA expression by RT-PCR of 91 genes reflecting tight junction proteins, chemokines, innate immunity, ion channels, transmitters, housekeeping genes, and controls for DNA contamination and PCR efficiency in small intestinal mucosa from 15 IBS-D and 7 controls (biopsies negative for celiac disease). Fold change was calculated using 2((-ΔΔCT)) formula...
September 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27438147/a-folate-receptor-targeted-lipoplex-delivering-interleukin-15-gene-for-colon-cancer-immunotherapy
#20
Xiao Liang, Min Luo, Xia-Wei Wei, Cui-Cui Ma, Yu-Han Yang, Bin Shao, Yan-Tong Liu, Ting Liu, Jun Ren, Li Liu, Zhi-Yao He, Yu-Quan Wei
Interleukin-15 has been implicated as a promising cytokine for cancer immunotherapy, while folate receptor α (FRα) has been shown to be a potentially useful target for colon cancer therapy. Herein, we developed F-PLP/pIL15, a FRα-targeted lipoplex loading recombinant interleukin-15 plasmid (pIL15) and studied its antitumor effects in vivo using a CT26 colon cancer mouse model. Compared with control (normal saline) treatment, F-PLP/pIL15 significantly suppressed tumor growth in regard to tumor weight (P < 0...
August 9, 2016: Oncotarget
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