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https://www.readbyqxmd.com/read/28921509/baff-augments-iga2-and-il-10-production-by-tlr7-8-stimulated-total-peripheral-blood-b-cells
#1
Gerco den Hartog, Thijs L J van Osch, Martijn Vos, Ben Meijer, Huub F J Savelkoul, R J Joost van Neerven, Sylvia Brugman
Class-switching of B cells to IgA can be induced via both T cell-dependent and T cell-independent mechanisms. IgA is most predominantly produced mucosally and is important for combating infections and allergies. In contrast to mice, humans have two forms of IgA; IgA1 and IgA2 with diverse tissue distribution. In early life, IgA levels might be sub-optimal especially during the fall season when bacterial and viral infections are more common. Therefore, we investigated using human B cells whether T cell-independent factors -promoting cell survival, class switching and immunoglobulin secretion- BAFF, APRIL, IL-10 and retinoic acid can boost IgA production in the context of viral or bacterial infection...
September 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28918392/cnvs-affecting-cancer-predisposing-genes-cpgs-detected-as-incidental-findings-in-routine-germline-diagnostic-chromosomal-microarray-cma-testing
#2
Josie Innes, Lisa Reali, Jill Clayton-Smith, Georgina Hall, Derek Hk Lim, George J Burghel, Kim French, Unzela Khan, Daniel Walker, Fiona Lalloo, D Gareth R Evans, Dominic McMullan, Eamonn R Maher, Emma R Woodward
BACKGROUND: Identification of CNVs through chromosomal microarray (CMA) testing is the first-line investigation in individuals with learning difficulties/congenital abnormalities. Although recognised that CMA testing may identify CNVs encompassing a cancer predisposition gene (CPG), limited information is available on the frequency and nature of such results. METHODS: We investigated CNV gains and losses affecting 39 CPGs in 3366 pilot index case individuals undergoing CMA testing, and then studied an extended cohort (n=10 454) for CNV losses at 105 CPGs and CNV gains at 9 proto-oncogenes implicated in inherited cancer susceptibility...
September 16, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28918263/dna-nanotechnology-based-composite-type-gold-nanoparticle-immunostimulatory-dna-hydrogel-for-tumor-photothermal-immunotherapy
#3
Tomoya Yata, Yuki Takahashi, Mengmeng Tan, Hirotaka Nakatsuji, Shozo Ohtsuki, Tatsuya Murakami, Hiroshi Imahori, Yuka Umeki, Tomoki Shiomi, Yoshinobu Takakura, Makiya Nishikawa
Success of tumor photothermal immunotherapy requires a system that induces heat stress in cancer cells and enhances strong anti-tumor immune responses. Here, we designed a composite-type immunostimulatory DNA hydrogel consisting of a hexapod-like structured DNA (hexapodna) with CpG sequences and gold nanoparticles. Mixing of the properly designed hexapodna and oligodeoxynucleotide-modified gold nanoparticles resulted in the formation of composite-type gold nanoparticle-DNA hydrogels. Laser irradiation of the hydrogel resulted in the release of hexapodna, which efficiently stimulated immune cells to release proinflammatory cytokines...
September 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/28918249/perinatal-depression-and-dna-methylation-of-oxytocin-related-genes-a-study-of-mothers-and-their-children
#4
Leonora King, Stephanie Robins, Gang Chen, Volodymyr Yerko, Yi Zhou, Corina Nagy, Nancy Feeley, Ian Gold, Barbara Hayton, Gustavo Turecki, Phyllis Zelkowitz
The present study investigated the association of perinatal depression (PD) with differential methylation of 3 genomic regions among mother and child dyads: exon 3 within the oxytocin receptor (OXTR) gene and 2 intergenic regions (IGR) between the oxytocin (OXT) and vasopressin (AVP) genes. Maternal PD was assessed at 5 time-points during pregnancy and postpartum. Four groups were established based on Edinburgh Postnatal Depression Scale (EPDS) cut-off scores: no PD, prenatal or postpartum depressive symptoms only and persistent PD (depressive symptoms both prenatally and postpartum)...
September 13, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28918040/codon-optimized-p1a-encoding-dna-vaccine-toward-a-therapeutic-vaccination-against-p815-mastocytoma
#5
Alessandra Lopes, Kevin Vanvarenberg, Véronique Préat, Gaëlle Vandermeulen
DNA vaccine can be modified to increase protein production and modulate immune response. To enhance the efficiency of a P815 mastocytoma DNA vaccine, the P1A gene sequence was optimized by substituting specific codons with synonymous ones while modulating the number of CpG motifs. The P815A murine antigen production was increased with codon-optimized plasmids. The number of CpG motifs within the P1A gene sequence modulated the immunogenicity by inducing a local increase in the cytokines involved in innate immunity...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918025/effect-of-calcium-carbonate-encapsulation-on-the-activity-of-orally-administered-cpg-oligonucleotides
#6
Neslihan Kayraklioglu, Julia Scheiermann, W Gregory Alvord, Dennis M Klinman
Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODNs) stimulate immune cells via Toll-like receptor 9 (TLR9). Because oligodeoxynucleotides (ODNs) are susceptible to gastric degradation, clinical trials designed to evaluate their therapeutic utility have relied solely on parenteral routes of administration. A strategy to improve the activity of orally delivered ODNs by reducing their susceptibility to gastrointestinal (GI) digestion via encapsulation in calcium carbonate nanoparticles (ODNcaps) was recently described...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916733/clonal-expansion-and-epigenetic-reprogramming-following-deletion-or-amplification-of-mutant-idh1
#7
Tali Mazor, Charles Chesnelong, Aleksandr Pankov, Llewellyn E Jalbert, Chibo Hong, Josie Hayes, Ivan V Smirnov, Roxanne Marshall, Camila F Souza, Yaoqing Shen, Pavithra Viswanath, Houtan Noushmehr, Sabrina M Ronen, Steven J M Jones, Marco A Marra, J Gregory Cairncross, Arie Perry, Sarah J Nelson, Susan M Chang, Andrew W Bollen, Annette M Molinaro, Henrik Bengtsson, Adam B Olshen, Samuel Weiss, Joanna J Phillips, H Artee Luchman, Joseph F Costello
IDH1 mutation is the earliest genetic alteration in low-grade gliomas (LGGs), but its role in tumor recurrence is unclear. Mutant IDH1 drives overproduction of the oncometabolite d-2-hydroxyglutarate (2HG) and a CpG island (CGI) hypermethylation phenotype (G-CIMP). To investigate the role of mutant IDH1 at recurrence, we performed a longitudinal analysis of 50 IDH1 mutant LGGs. We discovered six cases with copy number alterations (CNAs) at the IDH1 locus at recurrence. Deletion or amplification of IDH1 was followed by clonal expansion and recurrence at a higher grade...
September 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28916632/tissue-sex-and-age-specific-dna-methylation-of-rat-glucocorticoid-receptor-gene-promoter-and-insulin-like-growth-factor-2-imprinting-control-region
#8
Ogechukwu Brenda Agba, Ludwig Lausser, Klaus Huse, Christoph Bergmeier, Niels Jahn, Marco Groth, Martin Bens, Arne Sahm, Maria Gall, Otto W Witte, Hans A Kestler, Matthias Schwab, Matthias Platzer
Tissue-, sex- and age-specific epigenetic modifications such as DNA methylation are largely unknown. Changes in DNA methylation of the glucocorticoid receptor gene (NR3C1) and imprinting control region (ICR) of IGF2 and H19 genes during the lifespan are particularly interesting since these genes are susceptible to epigenetic modifications by prenatal stress or malnutrition. They are important regulators of development and aging. Methylation changes of NR3C1 affect glucocorticoid receptor expression, which is associated with stress sensitivity and stress-related diseases predominantly occurring during aging...
September 15, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28915890/barriers-and-enablers-for-the-development-and-implementation-of-allied-health-clinical-practice-guidelines-in-south-african-primary-healthcare-settings-a-qualitative-study
#9
J M Dizon, K Grimmer, Q Louw, S Machingaidze, H Parker, H Pillen
BACKGROUND: The South African allied health (AH) primary healthcare (PHC) workforce is challenged with the complex rehabilitation needs of escalating patient numbers. The application of evidence-based care using clinical practice guidelines (CPGs) is one way to make efficient and effective use of resources. Although CPGs are common for AH in high-income countries, there is limited understanding of how to do this in low- to middle-income countries. This paper describes barriers and enablers for AH CPG uptake in South African PHC...
September 15, 2017: Health Research Policy and Systems
https://www.readbyqxmd.com/read/28914964/clinicopathological-and-molecular-implications-of-aberrant-ttf-1-expression-in-colorectal-carcinomas-an-immunohistochemical-analysis-of-1-319-cases-using-three-different-antibody-clones
#10
Jeong Mo Bae, Jung Ho Kim, Jeong Hwan Park, Hye Eun Park, Nam-Yun Cho, Gyeong Hoon Kang
AIMS: The precise profile of aberrant expression of thyroid transcription factor-1 (TTF-1) according to antibody clones in colorectal carcinomas (CRCs) has been controversial. Moreover, the detailed clinicopathological and molecular features of CRCs with TTF-1 expression have rarely been investigated. Here, we evaluated the TTF-1 expression status in a large series of CRC cases using three different antibody clones. METHODS AND RESULTS: Immunohistochemistry for TTF-1 using clones 8G7G3/1, SPT24, and SP141 was performed on tumour tissues of 1,319 primary CRCs and 98 corresponding metastatic lesions...
September 15, 2017: Histopathology
https://www.readbyqxmd.com/read/28914317/a-bifunctional-nanomodulator-for-boosting-cpg-mediated-cancer-immunotherapy
#11
Zhenzhen Wang, Yan Zhang, Zhen Liu, Kai Dong, Chaoqun Liu, Xiang Ran, Fang Pu, Enguo Ju, Jinsong Ren, Xiaogang Qu
Unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides (ODNs) possess high immunostimulatory activity and represent attractive tools for cancer treatment. However, their success in eliminating large solid tumors was hampered by the immunosuppressive tumor microenvironment. Herein, we report that the design of a novel MnO2-CpG-silver nanoclusters (AgNCs)-doxorubicin (DOX) conjugate for enhanced cancer immunotherapy, in which MnO2 nanosheets function as unique supports to integrate the chemotherapy drug DOX and the immunotherapeutic agent CpG-AgNCs...
September 15, 2017: Nanoscale
https://www.readbyqxmd.com/read/28912777/class-a-cpg-oligonucleotide-priming-rescues-mice-from-septic-shock-via-activation-of-platelet-activating-factor-acetylhydrolase
#12
Yoshinari Yamamoto, Ryu Sugimura, Takafumi Watanabe, Suguru Shigemori, Takuma Okajima, Shireen Nigar, Fu Namai, Takashi Sato, Tasuku Ogita, Takeshi Shimosato
Sepsis is a life-threatening, overwhelming immune response to infection with high morbidity and mortality. Inflammatory response and blood clotting are caused by sepsis, which induces serious organ damage and death from shock. As a mechanism of pathogenesis, platelet-activating factor (PAF) induces excessive inflammatory responses and blood clotting. In this study, we demonstrate that a Class A CpG oligodeoxynucleotide (CpG-A1585) strongly induced PAF acetylhydrolase, which generates lyso-PAF. CpG-A1585 rescued mice from acute lethal shock and decreased fibrin deposition, a hallmark of PAF-induced disseminated intravascular coagulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28912774/therapeutic-antibodies-to-kir3dl2-and-other-target-antigens-on-cutaneous-t-cell-lymphomas
#13
REVIEW
Christian Schmitt, Anne Marie-Cardine, Armand Bensussan
KIR3DL2 is a member of the killer cell immunoglobulin-like receptor (KIR) family that was initially identified at the surface of natural killer (NK) cells. KIR3DL2, also known as CD158k, is expressed as a disulfide-linked homodimer. Each chain is composed of three immunoglobulin-like domains and a long cytoplasmic tail containing two immunoreceptor tyrosine-based inhibitory motifs. Beside its expression on NK cells, it is also found on rare circulating T lymphocytes, mainly CD8(+). Although the KIR gene number varies between haplotype, KIR3DL2 is a framework gene present in all individuals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28912427/dna-methylation-profiling-reveals-common-signatures-of-tumorigenesis-and-defines-epigenetic-prognostic-subtypes-of-canine-diffuse-large-b-cell-lymphoma
#14
Serena Ferraresso, Arianna Aricò, Tiziana Sanavia, Silvia Da Ros, Massimo Milan, Luciano Cascione, Stefano Comazzi, Valeria Martini, Mery Giantin, Barbara Di Camillo, Sandro Mazzariol, Diana Giannuzzi, Laura Marconato, Luca Aresu
Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5'-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28910750/analysis-of-methylation-profiling-data-of-hyperplasia-and-primary-and-metastatic-endometrial-cancers
#15
Xihai Wu, Jilan Miao, Jingyan Jiang, Fangmei Liu
OBJECTIVE: Endometrial cancer is a prevalent cancer, and its metastasis causes low survival rate. This study aims to utilize DNA methylation data to investigate the mechanism of the development and metastasis of endometrial cancer. STUDY DESIGN: Methylation profiling data were down-loaded from Gene Expression Omnibus, including 8 hyperplasias, 33 primary and 53 metastatic endometrial cancers. COHCAP package and annotation files were utilized to identify differentially methylated genes (DMGs) and CpG islands between the three different endometrial diseases...
September 1, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28910327/in-silico-analysis-of-cis-acting-regulatory-elements-of-pathogenesis-related-proteins-of-arabidopsis-thaliana-and-oryza-sativa
#16
Amritpreet Kaur, Pratap Kumar Pati, Aparna Maitra Pati, Avinash Kaur Nagpal
Pathogenesis related (PR) proteins are low molecular weight family of proteins induced in plants under various biotic and abiotic stresses. They play an important role in plant-defense mechanism. PRs have wide range of functions, acting as hydrolases, peroxidases, chitinases, anti-fungal, protease inhibitors etc. In the present study, an attempt has been made to analyze promoter regions of PR1, PR2, PR5, PR9, PR10 and PR12 of Arabidopsis thaliana and Oryza sativa. Analysis of cis-element distribution revealed the functional multiplicity of PRs and provides insight into the gene regulation...
2017: PloS One
https://www.readbyqxmd.com/read/28903739/evolving-dna-methylation-and-gene-expression-markers-of-b-cell-chronic-lymphocytic-leukemia-are-present-in-pre-diagnostic-blood-samples-more-than-10%C3%A2-years-prior-to-diagnosis
#17
Panagiotis Georgiadis, Irene Liampa, Dennie G Hebels, Julian Krauskopf, Aristotelis Chatziioannou, Ioannis Valavanis, Theo M C M de Kok, Jos C S Kleinjans, Ingvar A Bergdahl, Beatrice Melin, Florentin Spaeth, Domenico Palli, R C H Vermeulen, J Vlaanderen, Marc Chadeau-Hyam, Paolo Vineis, Soterios A Kyrtopoulos
BACKGROUND: B-cell chronic lymphocytic leukemia (CLL) is a common type of adult leukemia. It often follows an indolent course and is preceded by monoclonal B-cell lymphocytosis, an asymptomatic condition, however it is not known what causes subjects with this condition to progress to CLL. Hence the discovery of prediagnostic markers has the potential to improve the identification of subjects likely to develop CLL and may also provide insights into the pathogenesis of the disease of potential clinical relevance...
September 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28903050/changes-in-the-coding-and-non-coding-transcriptome-and-dna-methylome-that-define-the-schwann-cell-repair-phenotype-after-nerve-injury
#18
Peter J Arthur-Farraj, Claire C Morgan, Martyna Adamowicz, Jose A Gomez-Sanchez, Shaline V Fazal, Anthony Beucher, Bonnie Razzaghi, Rhona Mirsky, Kristjan R Jessen, Timothy J Aitman
Repair Schwann cells play a critical role in orchestrating nerve repair after injury, but the cellular and molecular processes that generate them are poorly understood. Here, we perform a combined whole-genome, coding and non-coding RNA and CpG methylation study following nerve injury. We show that genes involved in the epithelial-mesenchymal transition are enriched in repair cells, and we identify several long non-coding RNAs in Schwann cells. We demonstrate that the AP-1 transcription factor C-JUN regulates the expression of certain micro RNAs in repair Schwann cells, in particular miR-21 and miR-34...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28901819/dna-methylation-changes-in-human-lung-epithelia-cells-exposed-to-multi-walled-carbon-nanotubes
#19
Marta I Sierra, Laura Rubio, Gustavo F Bayón, Isabel Cobo, Pablo Menendez, Paula Morales, Cristina Mangas, Rocio G Urdinguio, Virginia Lopez, Adolfo Valdes, Gerard Vales, Ricard Marcos, Ramon Torrecillas, Agustin F Fernández, Mario F Fraga
Humans are increasingly exposed to nanoparticles and, although many of their physiological effects have been described, the molecular mechanisms underlying them are still largely unknown. The present study aimed to determine the possible role of certain epigenetic mechanisms in the cellular response of human lung epithelial cells that are triggered by long-term exposure to titanium dioxide nanoparticles (TiO2NPs) and multi-walled carbon nanotubes (MWCNTs). The results showed that exposure to TiO2NPs had only minor effects on genome-wide DNA methylation...
September 13, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28901751/sulfate-aerosols-promote-lung-cancer-metastasis-by-epigenetically-regulating-the-epithelial-to-mesenchymal-transition-emt
#20
Yang Yun, Rui Gao, Huifeng Yue, Lin Guo, Guangke Li, Nan Sang
Secondary inorganic aerosols (SIA), particularly sulfate aerosols, are central particulate matter (PM) constituents of severe haze formation in China and exert profound impacts on human health; however, our understanding of the mechanisms by which sulfate aerosols cause malignancy in lung carcinogenesis remains incomplete. Here, we show that exposure to secondary inorganic aerosols induced the invasion and migration of lung epithelial cells, and that (NH4)2SO4 exerted the most serious effects in vitro and promoted lung tumor metastasis in vivo...
September 13, 2017: Environmental Science & Technology
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