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immune epigenetic

Siroon Bekkering, Inge van den Munckhof, Tim Nielen, Evert Lamfers, Charles Dinarello, Joost Rutten, Jacqueline de Graaf, Leo A B Joosten, Mihai G Netea, Marc E R Gomes, Niels P Riksen
BACKGROUND AND AIMS: We have recently reported that monocytes can undergo functional and transcriptional reprogramming towards a long-term pro-inflammatory phenotype after brief in vitro exposure to atherogenic stimuli such as oxidized LDL. This process is termed 'trained immunity', and is mediated by epigenetic remodeling and a metabolic switch towards increased aerobic glycolysis. We hypothesize that trained immunity contributes to atherogenesis. Therefore, we investigated the inflammatory phenotype and epigenetic remodeling of monocytes from patients with and without established atherosclerosis...
October 12, 2016: Atherosclerosis
Walter H Moos, Carl A Pinkert, Michael H Irwin, Douglas V Faller, Krishna Kodukula, Ioannis P Glavas, Kosta Steliou
Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population...
October 20, 2016: Drug Development Research
David Olagnier, Cindy Chiang, John Hiscott
The dynamics of chromatin structure contribute to the regulation of gene transcription and in part, the changes in chromatin structure associated with gene activation/repression are a function of the state of histone acetylation. Histone deacetylases (HDACs) deacetylate histone tails leading to a more compact structure of chromatin that in turn represses gene transcription. Given the rapid activation and/or repression of gene networks following microbial infection, the role of HDACs in the epigenetic regulation of genes involved in the innate and adaptive immune responses has become an area of extensive research...
2017: Methods in Molecular Biology
Patricio Lopez-Jaramillo
Cardiovascular diseases (CVD) are major causes of death and illness worldwide. In recent decades an increased prevalence of CVD mortality has been reported in low-medium income countries, which has been associated with changes in life styles, deficiencies in health systems and the persistence of social inequities.The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with insulin resistance and increased adiposity as its central features. Identifying individuals with metabolic syndrome is important due to its association with an increased risk of coronary heart disease and type 2 diabetes mellitus (DM2)...
September 2016: Journal of Hypertension
Naoshi Nishida, Masatoshi Kudo
Accumulation of genetic and epigenetic alterations is a hallmark of cancer genomes, including those in hepatocellular carcinoma (HCC). Particularly, in human HCC, epigenetic changes are more frequently observed than genetic changes in a variety of cancer-related genes, suggesting a potential role for epigenetic alterations during hepatocarcinogenesis. Several environmental factors, such as inflammation, obesity, and steatosis, are reported to affect the epigenetic status in hepatocytes, which could play a role in HCC development...
2016: Digestive Diseases
Nageatte Ibrahim, Elizabeth I Buchbinder, Scott R Granter, Scott J Rodig, Anita Giobbie-Hurder, Carla Becerra, Argyro Tsiaras, Evisa Gjini, David E Fisher, F Stephen Hodi
Epigenetic alterations by histone/protein deacetylases (HDACs) are one of the many mechanisms that cancer cells use to alter gene expression and promote growth. HDAC inhibitors have proven to be effective in the treatment of specific malignancies, particularly in combination with other anticancer agents. We conducted a phase I trial of panobinostat in patients with unresectable stage III or IV melanoma. Patients were treated with oral panobinostat at a dose of 30 mg daily on Mondays, Wednesdays, and Fridays (Arm A)...
October 17, 2016: Cancer Medicine
Manojkumar Bupathi, Christina Wu
Colorectal cancer (CRC) is a heterogeneous disease for which the treatment backbone has primarily been cytotoxic chemotherapy. With better understanding of the involved molecular mechanisms, it is now known that there are a number of epigenetic and genetic events, which are involved in CRC pathogenesis. Specific biomarkers have been identified which can be used to determine the clinical outcome of patients beyond tumor staging and predict for treatment efficacy. Molecular testing is now routinely performed to select for patients that will benefit the most from targeted agents and immunotherapy...
October 2016: Journal of Gastrointestinal Oncology
Ivana V Yang, Brent S Pedersen, Andrew H Liu, George T O'Connor, Dinesh Pillai, Meyer Kattan, Rana Tawil Misiak, Rebecca Gruchalla, Stanley J Szefler, Gurjit K Khurana Hershey, Carolyn Kercsmar, Adam Richards, Allen D Stevens, Christena A Kolakowski, Melanie Makhija, Christine A Sorkness, Rebecca Z Krouse, Cynthia Visness, Elizabeth J Davidson, Corinne E Hennessy, Richard J Martin, Alkis Togias, William W Busse, David A Schwartz
BACKGROUND: Given the strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia might provide insight into allergic asthma. OBJECTIVE: We sought to identify DNA methylation and gene expression changes associated with childhood allergic persistent asthma. METHODS: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma (n = 36) versus healthy control subjects (n = 36)...
October 13, 2016: Journal of Allergy and Clinical Immunology
Keith M Godfrey, Rebecca M Reynolds, Susan L Prescott, Moffat Nyirenda, Vincent W V Jaddoe, Johan G Eriksson, Birit F P Broekman
In addition to immediate implications for pregnancy complications, increasing evidence implicates maternal obesity as a major determinant of offspring health during childhood and later adult life. Observational studies provide evidence for effects of maternal obesity on her offspring's risks of obesity, coronary heart disease, stroke, type 2 diabetes, and asthma. Maternal obesity could also lead to poorer cognitive performance and increased risk of neurodevelopmental disorders, including cerebral palsy. Preliminary evidence suggests potential implications for immune and infectious-disease-related outcomes...
October 10, 2016: Lancet Diabetes & Endocrinology
Maria C Cenit, Pilar Codoñer-Franch, Yolanda Sanz
Gut microbiota shapes the development of the mucosal immune system and may provide protection against immune-mediated diseases. Celiac disease (CD) is a chronic inflammatory condition triggered by dietary gluten proteins, recently associated with gut microbiota alterations in cross-sectional studies comparing patients and controls. Whether or not these differences are causally related to the disease has yet to be elucidated, but evaluation of specific bacteria isolated from CD patients in experimental models suggests that they can promote an adverse response to dietary gluten, whereas other commensal bacteria can be protective...
November 2016: Journal of Clinical Gastroenterology
I-Cheng Ho, Shi-Chuen Miaw
IL-4 was first identified as a T cell-derived growth factor for B cells. Studies over the past several decades have markedly expanded our understanding of its cellular sources and function. In addition to T cells, IL-4 is produced by innate lymphocytes, such as NTK cells, and myeloid cells, such as basophils and mast cells. It is a signature cytokine of type 2 immune response but also has a nonimmune function. Its expression is tightly regulated at several levels, including signaling pathways, transcription factors, epigenetic modifications, microRNA, and long noncoding RNA...
2016: Advances in Experimental Medicine and Biology
John Fenimore, Howard A Young
Interferon gamma, referred to here as IFN-γ, is a major component in immunological cell signaling and is a critical regulatory protein for overall immune system function. First discovered in 1965 (Wheelock Science 149: (3681)310-311, 1965), IFN-γ is the only Type II interferon identified. Its expression is both positively and negatively controlled by different factors. In this chapter, we will review the transcriptional and post-transcriptional control of IFN-γ expression. In the transcriptional control part, the regular activators and suppressors are summarized, we will also focus on the epigenetic control, such as chromosome access, DNA methylation, and histone acetylation...
2016: Advances in Experimental Medicine and Biology
Amanda R Dancsok, Karama Asleh-Aburaya, Torsten O Nielsen
The heterogeneity of sarcomas with regard to molecular genesis, histology, clinical characteristics, and response to treatment makes management of these rare yet diverse neoplasms particularly challenging. This review encompasses recent developments in sarcoma diagnostics and treatment, including cytotoxic, targeted, epigenetic, and immune therapy agents. In the past year, groups internationally explored the impact of adding mandatory molecular testing to histological diagnosis, reporting some changes in diagnosis and/or management; however, the impact on outcomes could not be adequately assessed...
October 9, 2016: Oncotarget
Yu Bin Shin, Jong Hoon Park
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common inherited disorders. It is the fourth leading cause of renal replacement and renal failure worldwide. Mutations in PKD1 or PKD2 cause ADPKD. Patients with ADPKD show progressive growth of renal cysts filled with cystic fluid, leading to end-stage renal disease (ESRD) and renal failure by their sixth decade of life. Currently, there are no curative treatments for ADPKD. Therefore, patients require dialysis or kidney transplantation...
2016: Advances in Experimental Medicine and Biology
Angela Zacharasiewicz
Maternal smoking in pregnancy (MSP) is a large modifiable risk factor for pregnancy related mortality and morbidity and also the most important known modifiable risk factor for asthma. This review summarises the effects of MSP throughout infancy, childhood and adolescence with regards to asthma (development and severity). Firstly, the direct damage caused by nicotine on fetal lung development, fetal growth and neuronal differentiation is discussed, as well as the indirect effects of nicotine on placental functioning...
July 2016: ERJ Open Research
Rob J W Arts, Mihai G Netea
The innate immune system is considered to have no immune memory. However, lately there has been as shift in paradigm. Cells of the innate immune system, and especially monocytes and macrophages, are capable of building a nonspecific memory, resulting in either better or worse responses to secondary stimulations/infections, as a result of epigenetic changes. This review gives a general overview of the at-the-moment available data.
August 2016: Microbiology Spectrum
Jun Udagawa, Kodai Hino
Epidemiological studies suggest that exposure to prenatal stressors, including malnutrition, maternal immune activation (MIA), and adverse life events, is associated with increased risks of schizophrenia, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD). However, the underlying pathophysiological mechanisms are unclear. The first trimester of pregnancy is particularly a vulnerable period. During this period, the self-renewal of neural stem cells and neurogenesis vigorously occur, and synaptic connections are partially formed in the telencephalon...
2016: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
Senthilkumar Sivanesan, Aaron Tan, Rebecca Jeyaraj, James Lam, Monica Gole, Antonio Hardan, Keyoumars Ashkan, Jayakumar Rajadas
Autism Spectrum Disorders (ASDs) are a group of complex neurodevelopmental conditions characterized by abnormal patterns of attention, and impaired social and communication skills. ASDs are also associated with a number of functional challenges and potentially harmful deficits, including restricted and repetitive behaviors, anxiety, irritability, seizures, and self-harm. Although the exact causes of ASDs are currently unknown, it is suggested that genetic, epigenetic and environmental factors play critical roles...
October 7, 2016: World Neurosurgery
Fang Zhang, Guiyou Liu, Yali Bu, Xiaofeng Ma, Junwei Hao
For the epigenetic characterization of myasthenia gravis (MG), we determined whether long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) are expressed differentially in subjects with and without MG. Compared with healthy control subjects, the MG patients had 1561 upregulated lncRNAs, 1034 downregulated lncRNAs, 921 upregulated mRNAs, and 806 downregulated mRNAs (fold change>2.0). Several GO terms including nucleic acid transcription factor activity, inflammatory response, regulation of leukocyte activation, lymphocyte proliferation and regulation of B cell proliferation were enriched in gene lists, suggesting a potential correlation with MG...
October 15, 2016: Journal of Neuroimmunology
Maximilian Stahl, Nathan Kohrman, Steven D Gore, Tae Kon Kim, Amer M Zeidan, Thomas Prebet
For several decades, we have known that epigenetic regulation is disrupted in cancer. Recently, an increasing body of data suggests epigenetics might be an intersection of current cancer research trends: next generation sequencing, immunology, metabolomics, and cell aging. The new emphasis on epigenetics is also related to the increasing production of drugs capable of interfering with epigenetic mechanisms and able to trigger clinical responses in even advanced phase patients. In this review, we will use myeloid malignancies as proof of concept examples of how epigenetic mechanisms can trigger or promote oncogenesis...
October 2016: PLoS Genetics
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