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https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#1
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28324774/methylation-changes-of-sirt1-klf4-dapk1-and-spg20-in-b-lymphocytes-derived-from-follicular-and-diffuse-large-b-cell-lymphoma
#2
Raffaele Frazzi, Eleonora Zanetti, Mariaelena Pistoni, Ione Tamagnini, Riccardo Valli, Luca Braglia, Francesco Merli
Diffuse large-B cell lymphomas (DLBCL) and follicular lymphomas (FL) are the most represented subtypes among mature B-cell neoplasms and originate from malignant B lymphocytes. Methylation represents one of the major epigenetic mechanisms of gene regulation. Silent information regulator 1 (SIRT1) is a class III lysine-deacetylase playing several functions and considered to be a context-dependent tumor promoter. We present the quantitative methylation, gene expression and tissue distribution of SIRT1 and some key mediators related to lymphoma pathogenesis in B lymphocytes purified from biopsies of follicular hyperplasias, FL and DLBCL...
March 9, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28324207/fructooligosaccharide-intake-promotes-epigenetic-changes-in-the-intestinal-mucosa-in-growing-and-ageing-rats
#3
Glaucia Carielo Lima, Vivian Cristine Correa Vieira, Cinthia Baú Betim Cazarin, Rafaela da Rosa Ribeiro, Stanislau Bogusz Junior, Cibele Lima de Albuquerque, Ramon Oliveira Vidal, Claudia Cardoso Netto, Áureo Tatsumi Yamada, Fabio Augusto, Mário Roberto Maróstica Junior
PURPOSE: The aim of this study was to investigate the relationship between fructooligosaccharide (FOS) intake at different life stages of Wistar rats and its stimulatory effects on intestinal parameters. METHODS: Recently weaned and ageing female rats were divided into growing and ageing treatments, which were fed diets that partially replaced sucrose with FOS for 12 weeks. RESULTS: Dietary FOS intake induced a significant increase in the numbers of Bifidobacterium and Lactobacillus in growing rats...
March 21, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28324153/epigenetics-in-the-pathogenesis-of-ra
#4
REVIEW
Caroline Ospelt, Steffen Gay, Kerstin Klein
Epigenetic modifications can stably alter gene expression and have been shown to be important in the maintenance of cell type-specific functions as well as in cell differentiation, e.g., in T and B cell maturation. In RA, alterations in DNA methylation, histone modifications, and microRNA expression have been found in immune as well as in stromal cells. These changes in the epigenome in RA patients influence key inflammatory and matrix-degrading pathways and are suspected to play a major role in the pathogenesis of RA...
March 21, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28324113/microrna-expression-patterns-involved-in-amyloid-beta-induced-retinal-degeneration
#5
Peirong Huang, Junran Sun, Fenghua Wang, Xueting Luo, Jingyang Feng, Qing Gu, Te Liu, Xiaodong Sun
Purpose: Dry age-related macular degeneration (AMD) is characterized by the accumulation of drusen under Bruch's membrane, and amyloid beta (Aβ) is speculated to be one of the key pathologic factors. While the detrimental effects of Aβ on retinas have been widely explored, Aβ-induced epigenetic regulatory changes have yet to be fully investigated. We therefore aimed to identify the microRNA (miRNA) expression profiles in an Aβ-induced mouse model of retinal degeneration. Methods: C57BL/6 mice were intravitreally injected with Aβ1-40 or PBS and the eye tissues were collected for hematoxylin and eosin (H&E) staining, apoptosis immunofluorescence staining, and miRNA profiling...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28324105/thyroid-hormone-dependent-epigenetic-regulation-of-melanocortin-4-receptor-levels-in-female-offspring-of-obese-rats
#6
T Tabachnik, T Kisliouk, A Marco, N Meiri, A Weller
Maternal obesity is a risk factor for offspring obesity. Melanocortin 4 receptor (Mc4r) is one of the mediators of food intake and energy balance. This study examines epigenetic mechanisms underlying altered Mc4r levels in the hypothalamic paraventricular nucleus in offspring of high-fat diet (HFD)-induced obese dams, and aims to elucidate the role of thyroid hormones in epigenetic regulation and tagging of their nucleosome at the Mc4r promoter. Female Wistar rats were fed HFD or chow from weaning through gestation and lactation...
January 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324041/line1-cpg-dna-hypomethylation-in-granulosa-cells-and-blood-leukocytes-is-associated-with-pcos-and-related-traits
#7
Pooja Sagvekar, Vijay Mangoli, Sadhana Desai, Anushree Patil, Srabani Mukherjee
CONTEXT: Altered global DNA methylation is indicative of epigenomic instability concerning chronic disease-states. Investigating its incidence and association with polycystic ovary syndrome (PCOS) is essential towards understanding the etiopathogenesis of this disorder. OBJECTIVES: To assess, global DNA methylation differences in peripheral blood leukocytes (PBLs) and cumulus granulosa cells (CGCs) of PCOS and controls and their association with PCOS and its traits...
January 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323978/assisted-reproductive-technologies-predispose-to-insulin-resistance-and-obesity-in-male-mice-challenged-with-a-high-fat-diet
#8
David Cerny, Claudio Sartori, Stefano F Rimoldi, Théo Meister, Rodrigo Soria, Elisa Bouillet, Urs Scherrer, Emrush Rexhaj
ART alters glucose homeostasis in mice and humans, but the underlying mechanisms are incompletely understood. ART induces endothelial dysfunction and arterial hypertension by epigenetic alteration of the eNOS gene. In eNOS deficient mice, insulin resistance is related to impaired insulin stimulation of muscle blood flow and substrate delivery and defective intrinsic skeletal muscle glucose uptake. We, therefore, assessed glucose tolerance, insulin sensitivity (euglycemic clamp), insulin stimulation of muscle blood flow in vivo and muscle glucose uptake in vitro in male ART and control mice fed a normal chow (NC) or challenged with a high fat diet (HFD) during 8 weeks...
February 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323958/jmjd3-is-crucial-for-female-avpv-rip-cre-neuron-controlled-kisspeptin-estrogen-feedback-loop-and-reproductive-function
#9
Anying Song, Shujun Jiang, Qinghua Wang, Jianghuan Zou, Zhaoyu Lin, Xiang Gao
The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. While most studies were focusing on the hierarch from brain to gonad, many questions remain unresolved concerning the feedback from gonad to the central nervous system, especially on the potential epigenetic modification in hypothalamic neurons. In this report, we generated genetically modified mice lacking histone H3 lysine 27 demethylase JMJD3 in hypothalamic RIP-Cre neurons. The female mutant mice display late-onset obesity due to reduced locomotor activity and decreased energy expenditure...
March 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323900/long-term-exposure-to-estrogen-enhances-chemotherapeutic-efficacy-potentially-through-epigenetic-mechanism-in-human-breast-cancer-cells
#10
Yu-Wei Chang, Kamaleshwar P Singh
Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2) on the efficacy of chemotherapeutic drugs in breast cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28320131/epigenetic-and-gene-expression-alterations-of-foxp3-in-the-t-cells-of-eae-mouse-model-of-multiple-sclerosis
#11
Ali Noori-Zadeh, Seyed Alireza Mesbah-Namin, Ali Akbar Saboor-Yaraghi
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319850/methylation-of-hpa-axis-related-genes-in-men-with-hypersexual-disorder
#12
Jussi Jokinen, Adrian E Boström, Andreas Chatzittofis, Diana M Ciuculete, Katarina Görts Öberg, John N Flanagan, Stefan Arver, Helgi B Schiöth
Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, and proposed as a diagnosis in the DSM 5, shares some overlapping features with substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. In this study, comprising 67 HD male patients and 39 male healthy volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality...
March 10, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28319609/developmental-alterations-in-huntington-s-disease-neural-cells-and-pharmacological-rescue-in-cells-and-mice
#13
(no author information available yet)
Neural cultures derived from Huntington's disease (HD) patient-derived induced pluripotent stem cells were used for 'omics' analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation...
March 20, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28319441/calorie-restriction-breaks-an-epigenetic-barrier-to-longevity
#14
Diego Molina-Serrano, Antonis Kirmizis
No abstract text is available yet for this article.
March 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28319413/aberrant-promoter-hypermethylation-of-p16-survivin-and-retinoblastoma-in-gastric-cancer
#15
L Guo, C Huang, Q J Ji
BACKGROUND: Gastric cancer is common and can be found throughout the world. Notoriously like other cancers, gastric cancer is a consequence of cellular regulation disorder. Epigenetics, including many oncogenes or tumour suppressor genes, can provide some clues for this kind of disorder. DNA methylation, especially promoter methylation, which causes the silence/decrease of tumour related genes, has become a focus in various tumour types. The aim of this study was to investigate promoter methylation of certain genes: p16, survivin, retinoblastoma (Rb), all of which have been regarded as genes related to gastric cancer...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28319137/the-h3k27-demethylase-utx-regulates-adipogenesis-in-a-differentiation-stage-dependent-manner
#16
Kazushige Ota, Kit I Tong, Kouichiro Goto, Shuta Tomida, Akiyoshi Komuro, Zhong Wang, Kazuto Nishio, Hitoshi Okada
Understanding the molecular mechanisms that drive adipogenesis is important in developing new treatments for obesity and diabetes. Epigenetic regulations determine the capacity of adipogenesis. In this study, we examined the role of a histone H3 lysine 27 demethylase, the ubiquitously transcribed tetratricopeptide repeat protein on the X chromosome (Utx), in the differentiation of mouse embryonic stem cells (mESCs) to adipocytes. Using gene trapping, we examined Utx-deficient male mESCs to determine whether loss of Utx would enhance or inhibit the differentiation of mESCs to adipocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28319045/akt-mediated-stabilization-of-histone-methyltransferase-whsc1-promotes-prostate-cancer-metastasis
#17
Ni Li, Wei Xue, Huairui Yuan, Baijun Dong, Yufeng Ding, Yongfeng Liu, Min Jiang, Shan Kan, Tongyu Sun, Jiale Ren, Qiang Pan, Xiang Li, Peiyuan Zhang, Guohong Hu, Yan Wang, Xiaoming Wang, Qintong Li, Jun Qin
Loss of phosphatase and tensin homolog (PTEN) and activation of the PI3K/AKT signaling pathway are hallmarks of prostate cancer (PCa). However, these alterations alone are insufficient for cells to acquire metastatic traits. Here, we have shown that the histone dimethyl transferase WHSC1 critically drives indolent PTEN-null tumors to become metastatic PCa. In a PTEN-null murine PCa model, WHSC1 overexpression in prostate epithelium cooperated with Pten deletion to produce a metastasis-prone tumor. Conversely, genetic ablation of Whsc1 prevented tumor progression in PTEN-null mice...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318821/snf2-family-protein-fft3-suppresses-nucleosome-turnover-to-promote-epigenetic-inheritance-and-proper-replication
#18
Nitika Taneja, Martin Zofall, Vanivilasini Balachandran, Gobi Thillainadesan, Tomoyasu Sugiyama, David Wheeler, Ming Zhou, Shiv I S Grewal
Heterochromatin can be epigenetically inherited in cis, leading to stable gene silencing. However, the mechanisms underlying heterochromatin inheritance remain unclear. Here, we identify Fft3, a fission yeast homolog of the mammalian SMARCAD1 SNF2 chromatin remodeler, as a factor uniquely required for heterochromatin inheritance, rather than for de novo assembly. Importantly, we find that Fft3 suppresses turnover of histones at heterochromatic loci to facilitate epigenetic transmission of heterochromatin in cycling cells...
March 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28318385/arsenic-induced-sumoylation-of-mus81-is-involved-in-regulating-genomic-stability
#19
Liyan Hu, Feikun Yang, Lou Lu, Wei Dai
Chronic environmental exposure to metal toxicants such as chromium and arsenic is closely related to the development of several types of common cancers. Genetic and epigenetic studies in the past decade reveal that post-translational modifications of histones play a role in metal carcinogenesis. However, exact molecular mechanisms of metal carcinogenesis remain to be elucidated. In this study we found that As2O3, an environmental metal toxicant, up-regulated overall modifications of many cellular proteins by SUMO2/3...
March 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28317902/a-natural-tandem-array-alleviates-epigenetic-repression-of-ipa1-and-leads-to-superior-yielding-rice
#20
Lin Zhang, Hong Yu, Bin Ma, Guifu Liu, Jianjun Wang, Junmin Wang, Rongcun Gao, Jinjun Li, Jiyun Liu, Jing Xu, Yingying Zhang, Qun Li, Xuehui Huang, Jianlong Xu, Jianming Li, Qian Qian, Bin Han, Zuhua He, Jiayang Li
Super hybrid rice varieties with ideal plant architecture (IPA) have been critical in enhancing food security worldwide. However, the molecular mechanisms underlying their improved yield remain unclear. Here, we report the identification of a QTL, qWS8/ipa1-2D, in the super rice Yongyou12 (YY12) and related varieties. In-depth genetic molecular characterization of qWS8/ipa1-2D reveals that this newly identified QTL results from three distal naturally occurring tandem repeats upstream of IPA1, a key gene/locus previously shown to shape rice ideal plant architecture and greatly enhance grain yield...
March 20, 2017: Nature Communications
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