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https://www.readbyqxmd.com/read/28102705/the-acetyl-code-in-rheumatoid-arthritis-and-other-rheumatic-diseases
#1
Chiara Angiolilli, Dominique L Baeten, Timothy R Radstake, Kris A Reedquist
Growing evidence supports the idea that aberrancies in epigenetic processes contribute to the onset and progression of human immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Epigenetic regulators of histone tail modifications play a role in chromatin accessibility and transcriptional responses to inflammatory stimuli. Among these, histone deacetylases (HDACs) regulate the acetylation status of histones and nonhistone proteins, essential for immune responses. Broad-spectrum HDAC inhibitors are well-known anti-inflammatory agents and reduce disease severity in animal models of arthritis; however, selective HDAC inhibitors remain poorly studied...
January 19, 2017: Epigenomics
https://www.readbyqxmd.com/read/28102058/neonatal-immune-state-is-influenced-by-maternal-allergic-rhinitis-and-associated-with-regulatory-t-cells
#2
Lu Tan, Jing Ou, Zezhang Tao, Yonggang Kong, Yu Xu
PURPOSE: Maternal influences contribute to the origin of allergic diseases, but the mechanisms are not clear. The current literature prompted the role of epigenetics in the development of allergic diseases. We sought to investigate the roles of regulatory T (Treg) cells and Forkhead box p3 (Foxp3) DNA methylation in the process of maternal transmission of allergic rhinitis (AR) susceptibility. METHODS: BALB/c female mice (AR mother) were sensitized by intraperitoneal injection of Dermatophagoides pteronyssinus (Der p) 1 on day 1 and 7...
March 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28100001/transplantation-tolerance-don-t-forget-about-the-b-cells
#3
REVIEW
Anita S Chong, Stella H Khiew
Establishing a state of transplantation tolerance that leads to indefinite graft survival without the need for lifelong immunosuppression has been successfully achieved in limited numbers of transplant recipients in the clinic. These successes led to studies aimed at identifying potential biomarkers that diagnose allograft tolerance and identify the patients most amenable to drug minimization, and implicated an enriched B cell signature of tolerance. The emergence of a specialized subset of regulatory B cell (Bregs) that possess immune-modulatory function in inflammation and autoimmune disease, raised the possibility that Bregs play critical roles in the promotion of transplantation tolerance and that Bregs are the underlying explanation for the B cell signature of tolerance...
January 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28099864/satb1-expression-governs-epigenetic-repression-of-pd-1-in-tumor-reactive-t-cells
#4
Tom L Stephen, Kyle K Payne, Ricardo A Chaurio, Michael J Allegrezza, Hengrui Zhu, Jairo Perez-Sanz, Alfredo Perales-Puchalt, Jenny M Nguyen, Ana E Vara-Ailor, Evgeniy B Eruslanov, Mark E Borowsky, Rugang Zhang, Terri M Laufer, Jose R Conejo-Garcia
Despite the importance of programmed cell death-1 (PD-1) in inhibiting T cell effector activity, the mechanisms regulating its expression remain poorly defined. We found that the chromatin organizer special AT-rich sequence-binding protein-1 (Satb1) restrains PD-1 expression induced upon T cell activation by recruiting a nucleosome remodeling deacetylase (NuRD) complex to Pdcd1 regulatory regions. Satb1 deficienct T cells exhibited a 40-fold increase in PD-1 expression. Tumor-derived transforming growth factor β (Tgf-β) decreased Satb1 expression through binding of Smad proteins to the Satb1 promoter...
January 17, 2017: Immunity
https://www.readbyqxmd.com/read/28098061/prostate-cancer-immunotherapy-particularly-in-combination-with-androgen-deprivation-or-radiation-treatment-customized-pharmacogenomic-approaches-to-overcome-immunotherapy-cancer-resistance
#5
REVIEW
C Alberti
Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation...
September 2017: Il Giornale di Chirurgia
https://www.readbyqxmd.com/read/28097530/virus-induced-hepatocellular-carcinoma-with-special-emphasis-on-hbv
#6
REVIEW
Ming Wang, Dong Xi, Qin Ning
Hepatocellular carcinoma (HCC) is a common malignant tumor with high lethality, and the hepatitis B virus (HBV) is a chief cause. HBV can accelerate HCC via multiple mechanisms. First, HBV induces immune reactions that lead to repeated hepatic inflammation, fibrosis and a deficient immune microenvironment. Subsequently, HBV can modify host genes near the insertion point through DNA integration to cause host cell genome instability and to generate carcinogenic fusion proteins. Additionally, HBV expresses diverse active proteins, especially HBx and HBs, which have a range of transactivation functions such as regulation of apoptosis, interference with intracellular signaling pathways, and alteration of epigenetics...
January 17, 2017: Hepatology International
https://www.readbyqxmd.com/read/28096407/development-of-chronic-allergic-responses-by-dampening-bcl6-mediated-suppressor-activity-in-memory-t-helper-2-cells
#7
Takashi Ogasawara, Masahiko Hatano, Hisae Satake, Jun Ikari, Toshibumi Taniguchi, Nobuhide Tsuruoka, Haruko Watanabe-Takano, Lisa Fujimura, Akemi Sakamoto, Hirokuni Hirata, Kumiya Sugiyama, Yasutsugu Fukushima, Susumu Nakae, Kenji Matsumoto, Hirohisa Saito, Takeshi Fukuda, Kazuhiro Kurasawa, Koichiro Tatsumi, Takeshi Tokuhisa, Masafumi Arima
Mice deficient in the transcriptional repressor B-cell CLL/lymphoma 6 (Bcl6) exhibit similar T helper 2 (TH2) immune responses as patients with allergic diseases. However, the molecular mechanisms underlying Bcl6-directed regulation of TH2 cytokine genes remain unclear. We identified multiple Bcl6/STAT binding sites (BSs) in TH2 cytokine gene loci. We found that Bcl6 is modestly associated with the BSs, and it had no significant effect on cytokine production in newly differentiated TH2 cells. Contrarily, in memory TH2 (mTH2) cells derived from adaptively transferred TH2 effectors, Bcl6 outcompeted STAT5 for binding to TH2 cytokine gene loci, particularly Interleukin4 (Il4) loci, and attenuated GATA binding protein 3 (GATA3) binding to highly conserved intron enhancer regions in mTH2 cells...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28093893/arabidopsis-thaliana-glutathione-s-transferase-theta-2-interacts-with-rsi1-fld-to-activate-systemic-acquired-resistance
#8
Zeeshan Zahoor Banday, Ashis Kumar Nandi
A partly infected plant develops systemic acquired resistance (SAR) and shows heightened resistance during subsequent infections. The infected parts generate certain mobile signals that travel to the distal tissues and help in activation of SAR. SAR is associated with epigenetic modifications of several defense-related genes. However, the mechanisms by which mobile signals contribute to epigenetic changes are little known. Previously we had shown that the Arabidopsis REDUCED SYSTEMIC IMMUNITY 1 (RSI1, alias FLOWERING LOCUS D; FLD), which codes for a putative histone demethylase is required for the activation of SAR...
January 17, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28093709/molecular-genetic-and-epigenetic-basis-of-multiple-sclerosis
#9
Zohreh Hojati
Multiple Sclerosis (MS) is a chronic immune-mediated disease of spinal cord and brain. The initial event in MS occurs when activated CD4(+) T cells in periphery exacerbates immune responses by stimulating immune cells such as B cells, CD8(+) cells, mast cells, granulocytes and monocytes. These proinflammatory cells pass blood brain barrier by secreting proinflammatory cytokines including TNF-α and INF-γ which activate adhesion factors. APCs (antigen-presenting cells) reactivate CD4(+) T cells after infiltrating the CNS and CD4(+) T cells produce cytokines and chemokines...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28088983/the-epigenetic-basis-of-hematopoietic-stem-cell-aging
#10
REVIEW
Ashley Kramer, Grant A Challen
Highly proliferative tissues such as the gut, skin, and bone marrow lose millions of cells each day to normal attrition and challenge from different biological adversities. To achieve a lifespan beyond the longevity of individual cell types, tissue-specific stem cells sustain these tissues throughout the life of a human. For example, the lifespan of erythrocytes is about 100 days and adults make about two million new erythrocytes every second. A small pool of hematopoietic stem cells (HSCs) in the bone marrow is responsible for the lifetime maintenance of these populations...
January 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28081255/changes-in-dna-methylation-in-mouse-lungs-after-a-single-intra-tracheal-administration-of-nanomaterials
#11
Ali M Tabish, Katrien Poels, Hyang-Min Byun, Katrien Luyts, Andrea A Baccarelli, Johan Martens, Stef Kerkhofs, Sven Seys, Peter Hoet, Lode Godderis
AIMS: This study aimed to investigate the effects of nanomaterial (NM) exposure on DNA methylation. METHODS AND RESULTS: Intra-tracheal administration of NM: gold nanoparticles (AuNPs) of 5-, 60- and 250-nm diameter; single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) at high dose of 2.5 mg/kg and low dose of 0.25 mg/kg for 48 h to BALB/c mice. Study showed deregulations in immune pathways in NM-induced toxicity in vivo. NM administration had the following DNA methylation effects: AuNP 60 nm induced CpG hypermethylation in Atm, Cdk and Gsr genes and hypomethylation in Gpx; Gsr and Trp53 showed changes in methylation between low- and high-dose AuNP, 60 and 250 nm respectively, and AuNP had size effects on methylation for Trp53...
2017: PloS One
https://www.readbyqxmd.com/read/28081217/collective-genetic-interaction-effects-and-the-role-of-antigen-presenting-cells-in-autoimmune-diseases
#12
Hyung Jun Woo, Chenggang Yu, Jaques Reifman
Autoimmune diseases occur when immune cells fail to develop or lose their tolerance toward self and destroy body's own tissues. Both insufficient negative selection of self-reactive T cells and impaired development of regulatory T cells preventing effector cell activation are believed to contribute to autoimmunity. Genetic predispositions center around the major histocompatibility complex (MHC) class II loci involved in antigen presentation, the key determinant of CD4+ T cell activation. Recent studies suggested that variants in the MHC region also exhibit significant non-additive interaction effects...
2017: PloS One
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#13
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28077626/low-dose-or-low-dose-rate-ionizing-radiation-induced-bioeffects-in-animal-models
#14
REVIEW
Feng Ru Tang, Weng Keong Loke, Boo Cheong Khoo
Animal experimental studies indicate that acute or chronic low-dose ionizing radiation (LDIR) (≤100 mSv) or low-dose-rate ionizing radiation (LDRIR) (<6 mSv/h) exposures may be harmful. It induces genetic and epigenetic changes and is associated with a range of physiological disturbances that includes altered immune system, abnormal brain development with resultant cognitive impairment, cataractogenesis, abnormal embryonic development, circulatory diseases, weight gain, premature menopause in female animals, tumorigenesis and shortened lifespan...
January 10, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28074830/tet1-in-nucleus-accumbens-opposes-depression-and-anxiety-like-behaviors
#15
Jian Feng, Catherine J Pena, Immanuel Purushothaman, Olivia Engmann, Deena Walker, Amber N Brown, Orna Issler, Marie Doyle, Eileen Harrigan, Ezekiell Mouzon, Vincent Vialou, Li Shen, Meelad M Dawlaty, Rudolf Jaenisch, Eric J Nestler
Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here, we examined a possible role for the DNA dioxygenase, ten eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28074529/epigenetic-mediated-immune-suppression-of-positive-co-stimulatory-molecules-in-chemoresistant-ovarian-cancer-cells
#16
Ercan Cacan
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity...
January 11, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28070760/the-generation-r-study-design-and-cohort-update-2017
#17
Marjolein N Kooijman, Claudia J Kruithof, Cornelia M van Duijn, Liesbeth Duijts, Oscar H Franco, Marinus H van IJzendoorn, Johan C de Jongste, Caroline C W Klaver, Aad van der Lugt, Johan P Mackenbach, Henriëtte A Moll, Robin P Peeters, Hein Raat, Edmond H H M Rings, Fernando Rivadeneira, Marc P van der Schroeff, Eric A P Steegers, Henning Tiemeier, André G Uitterlinden, Frank C Verhulst, Eppo Wolvius, Janine F Felix, Vincent W V Jaddoe
The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health from fetal life, childhood and young adulthood. This multidisciplinary study focuses on several health outcomes including behaviour and cognition, body composition, eye development, growth, hearing, heart and vascular development, infectious disease and immunity, oral health and facial growth, respiratory health, allergy and skin disorders of children and their parents...
December 2016: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28065745/alteration-of-methyl-cpg-binding-domain-family-in-patients-with-chronic-hepatitis-b
#18
Jing Zhao, Yu-Chen Fan, Long-Yan Chen, Shuai Gao, Feng Li, Kai Wang
BACKGROUND AND OBJECTIVE: Epigenetics contributes to the outcome of chronic hepatitis B virus (HBV) infection. However, the role of methyl-CpG binding domain (MBD) family in the natural history of chronic hepatitis B (CHB) has not been demonstrated. It is aimed to investigate the dynamic expression of MBD family and assess the potential association of MBD family in the progression of CHB. METHODS: Quantitative real-time polymerase chain reaction (RT-PCR) was used to determine the mRNA levels of MBD family in peripheral blood mononuclear cells (PBMCs) from 223 patients with CHB as training cohort, 146 patients with CHB as validation cohort [immune-tolerant (IT), immune clearance (IC), non/low-replicative (LR) and HBeAg negative hepatitis (ENH)], and 14 healthy controls (HCs)...
January 5, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28064082/novel-flavonol-analogues-as-potential-inhibitors-of-jmjd3-histone-demethylase-a-study-based-on-molecular-modelling
#19
Sanchari Basu Mallik, Aravinda Pai, Rekha R Shenoy, B S Jayashree
Epigenetic modulation of gene expression has drawn enormous attention among researchers globally in the present scenario. Since their discovery, Jmj-C histone demethylases were identified as useful markers in understanding the role of epigenetics in inflammatory conditions and in cancer as well. This has created arousal of interest in search of suitable candidates. Potential inhibitors from various other scaffolds such as hydroxyquinolines, hydroxamic acids and triazolopyridines have already been identified and reported...
December 13, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28062906/programmed-cell-death-1-pathway-inhibition-in-myeloid-malignancies-implications-for-myeloproliferative-neoplasms
#20
REVIEW
D C Choi, D Tremblay, C Iancu-Rubin, J Mascarenhas
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification...
January 6, 2017: Annals of Hematology
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