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Thaís L Oliveira, Kátia L Bacelo, Rodrigo A Schuch, Fabiana K Seixas, Tiago Collares, Oscar Ed Rodrigues, Josimar Vargas, Rafaella O do Nascimento, Odir A Dellagostin, Daiane D Hartwig
Immunisation with the C-terminal region of leptospiral immunoglobulin-like A protein (LigANI) has shown promising results against leptospirosis. We evaluated the humoral immune response and protection induced by LigANI associated with carboxyl multi-walled carbon nanotubes (COOH-MWCNTs), CpG oligodeoxynucleotides (CpG ODNs), or Alhydrogel. Animals immunised with CpG ODNs were unable to develop a humoral immune response, whereas immunisation with LigANI and COOH-MWCNTs produced a high level of IgG antibodies, similar to that with LigANI and Alhydrogel, but it was not protective...
October 13, 2016: Memórias do Instituto Oswaldo Cruz
Min Sun, Yinnan Mu, Yang Ding, Jingqun Ao, Xinhua Chen
Toll-like receptor 21 (TLR21) is a non-mammalian TLR that functions similar to mammalian TLR9 in recognizing CpG DNA. In the present study, we identified a TLR21 homologue, LycTLR21, from large yellow croaker (Larimichthys crocea). The complete coding sequence of LycTLR21 is 2946 nucleotides long, encoding a protein of 981 amino acids. The deduced LycTLR21 protein has typical TLR domain architecture, including a signal peptide, 13 leucine-rich repeats (LRRs) in the extracellular region, a transmembrane region, and a cytoplasmic Toll-Interleukin-1 receptor (TIR) domain...
October 14, 2016: Fish & Shellfish Immunology
Christopher A Benner, Erika Mora, Emily Mueller, F Jacob Seagull, Kelly Walkovich, Kaleena Johnson, Schuyler Halverson, Ed Rothman, George Hucks, John G Younger, Michele M Nypaver
OBJECTIVES: Febrile neutropenic pediatric patients are at heightened risk for serious bacterial infections, and rapid antibiotic administration (in <60 minutes) improves survival. Our objectives were to reduce the time-to-antibiotic (TTA) administration and to evaluate the effect of overall emergency department (ED) busyness on TTA. METHODS: This study was a quality improvement initiative with retrospective chart review to reduce TTA in febrile children with underlying diagnosis of cancer or hematologic immunodeficiency who visited the pediatric ED...
October 4, 2016: Pediatric Emergency Care
Yolande F M Ramos, Ingrid Meulenbelt
PURPOSE OF REVIEW: The purpose of this review is to provide an update of recent advances in the established role of different layers of epigenetic control mechanism that are used by joint cells to ensure tissue homeostasis and cope with changing microenvironment (e.g. ageing or disease). RECENT FINDINGS: New studies have further strengthened the evidence that joint tissue cells highly dependent on epigenetic control mechanisms, such as methylation at CpG-sites, noncoding RNAs and histone modifications to assure phenotypic plasticity and respective tissue homeostasis...
October 5, 2016: Current Opinion in Rheumatology
Ornella Affinito, Giovanni Scala, Domenico Palumbo, Ermanno Florio, Antonella Monticelli, Gennaro Miele, Vittorio Enrico Avvedimento, Alessandro Usiello, Lorenzo Chiariotti, Sergio Cocozza
DNA methylation is often analyzed by reporting the average methylation degree of each cytosine. In this study, we used a single molecule methylation analysis in order to look at the methylation conformation of individual molecules. Using D-aspartate oxidase as a model gene, we performed an in-depth methylation analysis through the developmental stages of three different mouse tissues (brain, lung, and gut), where this gene undergoes opposite methylation destiny. This approach allowed us to track both methylation and demethylation processes at high resolution...
October 17, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Raúl Alelú-Paz, Francisco J Carmona, José V Sanchez-Mut, Ariel Cariaga-Martínez, Ana González-Corpas, Nadia Ashour, Maria J Orea, Ana Escanilla, Alfonso Monje, Carmen Guerrero Márquez, Jerónimo Saiz-Ruiz, Manel Esteller, Santiago Ropero
Attempts to discover genes that are involved in the pathogenesis of major psychiatric disorders have been frustrating and often fruitless. Concern is building about the need to understand the complex ways in which nature and nurture interact to produce mental illness. We analyze the epigenome in several brain regions from schizophrenic patients with severe cognitive impairment using high-resolution (450K) DNA methylation array. We identified 139 differentially methylated CpG sites included in known and novel candidate genes sequences as well as in and intergenic sequences which functions remain unknown...
2016: Frontiers in Psychology
Zheng Jun Li, Dae-Kyoung Choi, Kyung-Cheol Sohn, Seul Ki Lim, Myung Im, Young Lee, Young-Joon Seo, Chang Deok Kim, Jeung-Hoon Lee
BACKGROUND: Interleukin-17A (IL-17A) is mainly secreted from Th17 cells that are activated by various stimuli including CpG oligodeoxynucleotide, a Toll-like receptor 9 (TLR9) ligand. Recently, it has been demonstrated that keratinocytes play an important role in the pathogenesis of psoriasis. OBJECTIVE: To investigate the potential role of keratinocytes, we examined whether TLR9 ligand CpG induces IL-17A expression in keratinocytes. METHODS: We used HaCaT keratinocytes as a model system, and determined CpG-induced IL-17A using enzyme-linked immunosorbent assay and Western blot...
October 2016: Annals of Dermatology
Yoshiki Nando, Jiro Watari, Chiyomi Ito, Ken Hara, Takahisa Yamasaki, Takuya Okugawa, Takashi Kondo, Tomoaki Kono, Katsuyuki Tozawa, Toshihiko Tomita, Yoshio Ohda, Tadayuki Oshima, Hirokazu Fukui, Nagahide Matsubara, Naohiro Tomita, Seiichi Hirota, Hiroto Miwa
It is recommended that small (6-10 mm) lesions be treated with endoscopic resection (ER), while diminutive (≤ 5 mm) lesions are not currently an indication for ER according to the Japanese guidelines. The aim of this study was to evaluate the molecular alterations, and therefore treatment indications, in diminutive vs. small tubular adenoma (TA). We prospectively analyzed genetic instability, including microsatellite instability (MSI) and loss of heterozygosity, methylation status, KRAS/BRAF mutations, and Ki-67 staining in 96 TAs without a villous component...
October 13, 2016: Human Pathology
David Agustriawan, Chien-Hung Huang, Jim Jinn-Chyuan Sheu, Shan-Chih Lee, Jeffrey J P Tsai, Nilubon Kurubanjerdjit, Ka-Lok Ng
Epigenetic regulation has been linked to the initiation and progression of cancer. Aberrant expression of microRNAs (miRNAs) is one such mechanism that can activate or silence oncogenes (OCGs) and tumor suppressor genes (TSGs) in cells. A growing number of studies suggest that miRNA expression can be regulated by methylation modification, thus triggering cancer development. However, there is no comprehensive in silico study concerning miRNA regulation by direct DNA methylation in cancer. Ovarian serous cystadenocarcinoma (OSC) was therefore chosen as a tumor model for the present work...
October 1, 2016: Computational Biology and Chemistry
Jezkova Eva, Kajo Karol, Zubor Pavol, Grendar Marian, Malicherova Bibiana, Mendelova Andrea, Dokus Karol, Lasabova Zora, Plank Lukas, Danko Jan
Breast cancer is a heterogeneous disease with very different responses to therapy and different length of survival. In many cases, however, the determination of the stage and histopathological characteristics of breast cancer is insufficient to predict prognosis and response to treatment for the vast heterogeneity of the disease. To understand the molecular signature of subtypes of breast cancer, we attempted to identify the methylation status of key tumour suppressor gene Ras association (RalGDS/AF-6) domain family member 1 isoform a (RASSF1A) and a member of the paired-like homeodomain transcription factor family which functions in left-right asymmetry development (PITX2) and to correlate results with known clinicopathological features of breast cancer...
October 15, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jennifer Gamboa Jackman, Hemraj Juwarker, Luke P Poveromo, Howard Levinson, Kam W Leong, Bruce A Sullenger
Dying cells release nucleic acids (NA) and NA-containing complexes that activate inflammatory pathways of immune cells. Sustained activation of these pathways contributes to chronic inflammation frequently encountered in autoimmune and inflammatory diseases. In this study, grafting of cationic polymers onto a nanofibrous mesh enabled local scavenging of negatively charged pro-inflammatory molecules in the extracellular space. Nucleic acid scavenging nanofibers (NASFs) formed from poly(styrene-alt-maleic anhydride) conjugated with 1...
October 14, 2016: Biomacromolecules
Emilio A Herrera, Francisca Cifuentes-Zúñiga, Esteban Figueroa, Cristian Villanueva, Cherie Hernández, René Alegría, Viviana Arroyo, Estefania Peñaloza, Marcelo Farías, Ricardo Uauy, Paola Casanello, Bernardo J Krause
In humans, intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial programming in umbilical vessels. We aimed to determine the effects of maternal antioxidant treatment with N-acetyl cysteine (NAC) on fetal endothelial function and eNOS programming in IUGR guinea pigs. IUGR was induced by implanting ameroid constrictors on uterine arteries of pregnant guinea pigs at mid gestation, receiving half of the sows NAC in the drinking water (from day 34 until term)...
October 14, 2016: Journal of Physiology
Susanne A Bengesser, Eva Z Reininghaus, Nina Lackner, Armin Birner, Frederike T Fellendorf, Martina Platzer, Nora Kainzbauer, Bernhard Tropper, Christa Hörmanseder, Robert Queissner, Hans-Peter Kapfhammer, Sandra J Wallner-Liebmann, Robert Fuchs, Erwin Petek, Christian Windpassinger, Mario Schnalzenberger, Bernd Reininghaus, Bernd Evert, Andreas Waha
OBJECTIVES: The clock gene ARNTL is associated with the transcription activation of monoamine oxidase A according to previous literature. Thus, we hypothesised that methylation of ARNTL may differ between bipolar disorder (BD) and controls. METHODS: The methylation status of one CpG island covering the first exon of ARNTL (PS2) and one site in the 5' region of ARNTL (cg05733463) were analysed in patients with BD (n = 151) versus controls (n = 66). Methylation analysis was performed by bisulphite-conversion of DNA from fasting blood with the EpiTect Bisulfite Kit, PCR and pyrosequencing...
October 14, 2016: World Journal of Biological Psychiatry
Xin Li, Yun Liu, Tal Salz, Kasper D Hansen, Andrew P Feinberg
DNA methylation at the 5-postion of cytosine (5mC) is an epigenetic modification that regulates gene expression and cellular plasticity in development and disease. The ten-eleven translocation (TET) gene family oxidizes 5mC to 5-hydroxymethylcytosine (5hmC), providing an active mechanism for DNA demethylation, and may also provide its own regulatory function. Here we applied oxidative bisulfite sequencing to generate whole-genome DNA methylation and hydroxymethylation maps at single-base resolution in paired human liver and lung normal and cancer...
October 13, 2016: Genome Research
Ruoxu Dou, Reiko Nishihara, Yin Cao, Tsuyoshi Hamada, Kosuke Mima, Atsuhiro Masuda, Yohei Masugi, Yan Shi, Mancang Gu, Wanwan Li, Annacarolina da Silva, Katsuhiko Nosho, Xuehong Zhang, Jeffrey A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis...
October 13, 2016: Cancer Immunology Research
Chamraj Kaewraemruaen, Rasana W Sermswan, Surasakdi Wongratanacheewin
Opisthorchis viverrini, a human liver fluke, is still an endemic parasitic infection in Thailand and nearly all countries in Southeast Asia. O. viverrini induces a chronic stage of infection in hamsters. During the first 2 weeks of infection, Th1 inducing cytokine, IL-12, increased but was down regulated in chronic infection. In this study it was found that unmethylated-CpG ODN (oligodeoxynucleotides) 1826 increased hamster mononuclear cell proliferation and stimulated IFN-γ production in vitro. The IFN-γ levels in hamster sera were significantly increased in hamsters injected with CpG ODN 1826 alone or plus crude somatic antigens (CSAg)...
October 11, 2016: Acta Tropica
Jonathan Hetzel, Sascha H Duttke, Christopher Benner, Joanne Chory
Transcriptional regulation of gene expression is a major mechanism used by plants to confer phenotypic plasticity, and yet compared with other eukaryotes or bacteria, little is known about the design principles. We generated an extensive catalog of nascent and steady-state transcripts in Arabidopsis thaliana seedlings using global nuclear run-on sequencing (GRO-seq), 5'GRO-seq, and RNA-seq and reanalyzed published maize data to capture characteristics of plant transcription. De novo annotation of nascent transcripts accurately mapped start sites and unstable transcripts...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Kim-Lin Chiew, Shanley Chong, Kirsten J Duggan, Nasreen Kaadan, Shalini K Vinod
AIM: To investigate adherence to clinical practice guidelines (CPGs) in cervical cancer and the correlation with clinical outcomes. METHODS: A retrospective analysis was conducted using patient information from a population-based cancer registry (2005-2011, n = 208). Compliance to 10 widely accepted CPGs was assessed. Univariate and multivariate analyses were performed to assess sociodemographic factors associated with CPG adherence. Multivariate Cox regression was performed to assess the relationship between CPG adherence and 5-year survival...
October 11, 2016: Asia-Pacific Journal of Clinical Oncology
Inessa Skrypkina, Liudmyla Tsyba, Kateryna Onyshchenko, Dmytro Morderer, Olena Kashparova, Oleksii Nikolaienko, Grigory Panasenko, Sergii Vozianov, Alina Romanenko, Alla Rynditch
The critical point for successful treatment of cancer is diagnosis at early stages of tumor development. Cancer cell-specific methylated DNA has been found in the blood of cancer patients, indicating that cell-free DNA (cfDNA) circulating in the blood is a convenient tumor-associated DNA marker. Therefore methylated cfDNA can be used as a minimally invasive diagnostic marker. We analysed the concentration of plasma cfDNA and methylation of six tumor suppressor genes in samples of 27 patients with renal cancer and 15 healthy donors as controls...
2016: Disease Markers
Janine Margarita Dizon, Karen Grimmer, Shingai Machingaidze, Pam McLaren, Quinette Louw
BACKGROUND: Little is known about allied health (AH) clinical practice guideline (CPG) activity in South Africa, and particularly in relation to primary health care (PHC). This paper reports on a scoping study undertaken to establish a reference framework, from which a comprehensive maximum variation sample could be selected. This was required to underpin robust sampling for a qualitative study aimed at understanding South African primary care AH therapy CPG activities. This paper builds on findings from the South African Guidelines Evaluation (Project SAGE) Flagship grant...
October 10, 2016: Health Research Policy and Systems
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