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https://www.readbyqxmd.com/read/28329817/early-life-benzo-a-pyrene-exposure-causes-neurodegenerative-syndromes-in-adult-zebrafish-danio-rerio-and-the-mechanism-involved
#1
Dongxu Gao, Chonggang Wang, Zhihui Xi, Yixi Zhou, Yuanchuan Wang, Zhenghong Zuo
There is increasing recognition of the importance of early-life environmental exposures in health disorders at later-life stages. The aim of this study was to evaluate whether early-life exposure to benzo[a]pyrene (BaP) could induce neurodegenerative syndromes at later-life stages in zebrafish. Embryos were exposed to BaP at doses of 0, 0.05, 0.5, 5, and 50 nM from early embryogenesis to 96 h post-fertilization (hpf), then transferred to clean water and maintained for 365 days. We found that BaP decreased locomotor and cognitive ability, neurotransmitter levels of dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine; and induced loss of dopaminergic neurons and resulted in neurodegeneration...
January 30, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28323001/dna-methyltransferase-1-rs16999593-genetic-polymorphism-decreases-risk-in-patients-with-transposition-of-great-arteries
#2
Liming Lei, Haoming Lin, Shilong Zhong, Zhiwei Zhang, Jimei Chen, Xiyong Yu, Xiaoqing Liu, Cheng Zhang, Zhiqiang Nie, Jian Zhuang
Complete transposition of the great arteries (TGA) is the most frequent cyanotic heart defect diagnosed in neonates. However, the exact etiology of TGA is unknown. The aim of the present study was to assess the association of TGA pathogenesis with single nucleotide polymorphisms (SNPs) in DNA methyltransferases (DNMTs)-1 and 3a- in Chinese children. We genotyped 5 SNPs (rs16999593, rs16999358, and rs2228611 in DNMT1; and rs2276599 and rs2276598 in DNMT3A) in 206 patients with complete TGA and 252 healthy children...
March 16, 2017: Gene
https://www.readbyqxmd.com/read/28321121/dnmt3a-regulates-t-cell-development-and-suppresses-t-all-transformation
#3
A C Kramer, A Kothari, W C Wilson, H Celik, J Nikitas, C Mallaney, E L Ostrander, E Eultgen, A Martens, M C Valentine, A L Young, T E Druley, M E Figueroa, B Zhang, G A Challen
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm resulting from the malignant transformation of T-cell progenitors, and comprises approximately 15 and 25% of pediatric and adult ALL cases respectively. It is well-established that activating NOTCH1 mutations are the major genetic lesions driving T-ALL in most patients, but efforts to develop targeted therapies against this pathway have produced limited success in decreasing leukemic burden and come with significant clinical side effects...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28315400/multicolor-flow-cytometry-and-multi-gene-next-generation-sequencing-are-complementary-and-highly-predictive-for-relapse-in-acute-myeloid-leukemia-following-allogeneic-transplant
#4
Bartlomiej M Getta, Sean M Devlin, Ross L Levine, Maria E Arcila, Abhinita S Mohanty, Ahmet Zehir, Martin S Tallman, Sergio A Giralt, Mikhail Roshal
Minimal Residual disease (MRD) in acute myeloid leukemia (AML) is typically measured using multi-parameter flow cytometry (MFC). Detection of leukemia mutations using multi-gene next generation sequencing (NGS) can potentially be used to measure residual disease. We used a targeted 28-gene NGS panel to detect mutations and different-from-normal 10-colour MFC to measure MRD in AML patients before allogeneic hematopoietic stem cell transplant (HCT). Residual disease was defined when any abnormal blast population was detected using MFC and when any leukemia allele was detected with a variant allele frequency (VAF) ≥5% using NGS...
March 14, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28303350/immunohistochemical-evaluation-of-klotho-and-dna-methyltransferase-3a-in-oral-squamous-cell-carcinomas
#5
Bhoj Raj Adhikari, Osamu Uehara, Hirofumi Matsuoka, Rie Takai, Fumiya Harada, Masafumi Utsunomiya, Takatoshi Chujo, Tetsuro Morikawa, Mamata Shakya, Koki Yoshida, Jun Sato, Toshiya Arakawa, Michiko Nishimura, Hiroki Nagayasu, Itsuo Chiba, Yoshihiro Abiko
Carcinoma follows a course of multiple changes that are affected by several important factors, with epigenetic silencing of the promoter gene being one of them. A series of studies have suggested that epigenetic changes in the anti-aging gene Klotho may be one of the emerging areas of concern in the study of carcinogenesis. We hypothesized that epigenetic silencing of Klotho due to hypermethylation of DNMT3a may be one of the causes of carcinoma in the oral and maxillofacial region. In this study, we analyzed the immunohistochemical expressions of Klotho and DNMT3a in tissues obtained from oral dysplasia and oral squamous cell carcinoma...
March 16, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28300839/bidirectional-transcription-of-linc00441-and-rb1-via-h3k27-modification-dependent-way-promotes-hepatocellular-carcinoma
#6
Junwei Tang, Yu Xie, Xiaoliang Xu, Yin Yin, Runqiu Jiang, Lei Deng, Zhongming Tan, Venkatanarayana Gangarapu, Jinhai Tang, Beicheng Sun
The retinoblastoma gene (RB1), a known tumor-suppressor gene (TSG), was decreased in multiple cancers including hepatocellular carcinoma (HCC). Here we focused on the bidirectional transcripted long noncoding RNA (Linc00441) with neighbor gene RB1 to investigate whether Linc00441 is involved in the suppression of RB1 in HCC. We found that aberrant upregulated intranuclear Linc00441 was reversely correlated with RB1 expression in human HCC samples. The gain- and loss-of-function investigation revealed that Linc00441 could promote the proliferation of HCC cells in vitro and in vivo with an apoptosis suppression and cell cycle rearrangement...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28297624/genomics-of-acute-myeloid-leukemia-diagnosis-and-pathways
#7
Lars Bullinger, Konstanze Döhner, Hartmut Döhner
In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28288143/dnmt3a-mutations-mediate-the-epigenetic-reactivation-of-the-leukemogenic-factor-meis1-in-acute-myeloid-leukemia
#8
H J Ferreira, H Heyn, M Vizoso, C Moutinho, E Vidal, A Gomez, A Martínez-Cardús, L Simó-Riudalbas, S Moran, E Jost, M Esteller
No abstract text is available yet for this article.
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28286768/epigenetic-guardian-a-review-of-the-dna-methyltransferase-dnmt3a-in-acute-myeloid-leukaemia-and-clonal-haematopoiesis
#9
REVIEW
Sabah F Chaudry, Timothy J T Chevassut
Acute myeloid leukaemia (AML) is a haematological malignancy characterized by clonal stem cell proliferation and aberrant block in differentiation. Dysfunction of epigenetic modifiers contributes significantly to the pathogenesis of AML. One frequently mutated gene involved in epigenetic modification is DNMT3A (DNA methyltransferase-3-alpha), a DNA methyltransferase that alters gene expression by de novo methylation of cytosine bases at CpG dinucleotides. Approximately 22% of AML and 36% of cytogenetically normal AML cases carry DNMT3A mutations and around 60% of these mutations affect the R882 codon...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28285987/tgf%C3%AE-incurred-epigenetic-aberrations-of-mirna-and-dna-methyltransferase-suppress-klotho-and-potentiate-renal-fibrosis
#10
Shasha Yin, Qin Zhang, Jun Yang, Wenjun Lin, Yanning Li, Fang Chen, Wangsen Cao
Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications such as aberrant miRNA and DNA methylation. Klotho is an anti-aging and anti-fibrotic protein and its early decline after renal injury is reportedly associated with aberrant DNA methylation. However, the key upstream pathological mediators and the molecular cascade leading to epigenetic Klotho suppression are not appreciably established. Here we investigate the epigenetic mechanism of Klotho deficiency and its functional relevance in renal fibrogenesis...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28278502/kaempferol-modulates-dna-methylation-and-downregulates-dnmt3b-in-bladder-cancer
#11
Wei Qiu, Jun Lin, Yichen Zhu, Jian Zhang, Liping Zeng, Ming Su, Ye Tian
BACKGROUND: Genomic DNA methylation plays an important role in both the occurrence and development of bladder cancer. Kaempferol (Kae), a natural flavonoid that is present in many fruits and vegetables, exhibits potent anti-cancer effects in bladder cancer. Similar to other flavonoids, Kae possesses a flavan nucleus in its structure. This structure was reported to inhibit DNA methylation by suppressing DNA methyltransferases (DNMTs). However, whether Kae can inhibit DNA methylation remains unclear...
March 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28273636/mir-30b-5p-acts-as-a-tumor-suppressor-repressing-cell-proliferation-and-cell-cycle-in-human-hepatocellular-carcinoma
#12
Xian Qin, Jing Chen, Long Wu, Zhisu Liu
MicroRNAs have been verified to participate in various biological behaviors of different tumors, via multiple signaling pathways. Many kinds of microRNAs in hepatocellular carcinoma have been researched. However, miR-30b-5p hasn't been included. Our study aim at the impacts of miR-30b-5p on HCC and the pathway it mediating. The results showed miR-30b-5p was significant downregulated in HCC tissues and cell lines. With clinical data, we've discovered miR-30b-5p was correlated with several clinical pathological characteristics, such as survival time, tumor size, HBV infected, pathological stage, differentiation and intrahepatic metastasis...
March 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28270689/dna-methyltransferase-dnmt3a-contributes-to-neuropathic-pain-by-repressing-kcna2-in-primary-afferent-neurons
#13
Jian-Yuan Zhao, Lingli Liang, Xiyao Gu, Zhisong Li, Shaogen Wu, Linlin Sun, Fidelis E Atianjoh, Jian Feng, Kai Mo, Shushan Jia, Brianna Marie Lutz, Alex Bekker, Eric J Nestler, Yuan-Xiang Tao
Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28270006/-effects-of-dietary-monosodium-glutamate-on-gene-expression
#14
Júlia Vanda Jurasek, László Bence Raposa, Andrea Gubicskóné Kisbenedek, Veronika Varga, Zoltán Szabó, Tímea Varjas
INTRODUCTION: Nowadays, the food industry more often uses different type of additives during the food production. AIM: Our aim was to examine the monosodium-glutamate's effect (in animal experiment) on DNA-methyltransferases in gene expression patterns of mRNA levels. MATERIALS AND METHOD: In the investigation we used 24 (n=24) CD1 type female mice. The animals were fed with different equivalent human doses of the tested substance. After autopsy, mRNA was isolated from different tissues (lung, liver, kidney, spleen)...
March 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28267064/nerve-injury-induced-epigenetic-silencing-of-opioid-receptors-controlled-by-dnmt3a-in-primary-afferent-neurons
#15
Linlin Sun, Jian-Yuan Zhao, Xiyao Gu, Lingli Liang, Shaogen Wu, Kai Mo, Jian Feng, Weixiang Guo, Jun Zhang, Alex Bekker, Xinyu Zhao, Eric J Nestler, Yuan-Xiang Tao
Opioids are the gold standard for pharmacological treatment of neuropathic pain, but their analgesic effects are unsatisfactory in part due to nerve injury-induced downregulation of opioid receptors in dorsal root ganglia (DRG) neurons. How nerve injury drives such downregulation remains elusive. DNA methyltransferase-(DNMT-) triggered DNA methylation represses gene expression. We show here that blocking the nerve injury-induced increase in DRG DNMT3a (a de novo DNMT) rescued the expression of Oprm1 and Oprk1 mRNAs and their respective encoding mu opioid receptor (MOR) and kappa opioid receptor (KOR) proteins in the injured DRG...
March 4, 2017: Pain
https://www.readbyqxmd.com/read/28262826/epigenetic-modifications-of-interleukin-6-in-synovial-fibroblasts-from-osteoarthritis-patients
#16
Fei Yang, Song Zhou, Chuandong Wang, Yan Huang, Huiwu Li, You Wang, Zhenan Zhu, Jian Tang, Mengning Yan
Osteoarthritis (OA) is the most common degenerative disease of the synovial joint. The synovial membrane is responsible for the inflammatory reaction leading to the secretion of macrophage-derived pro-inflammatory cytokines, such as IL-6. Suppressing IL-6 over-expression in synovial fibroblasts (SF) is a promising method to prevent OA development and progression, in which the prerequisite is the elucidation of the molecular mechanisms underlying IL-6 over-expression in SF. Currently, there are few reports concerning epigenetic modifications in IL-6 in OA SF...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257867/cobalamin-supplementation-during-in%C3%A2-vitro-maturation-improves-developmental-competence-of-sheep-oocytes
#17
Federica Zacchini, Paola Toschi, Grazyna Ewa Ptak
Pregnancies obtained by Assisted Reproductive Technologies are at higher risk of miscarriage than those obtained naturally. Previously, we reported impaired placental vascular development of in vitro produced (IVP) sheep embryos and defective DNA methylation in the placentae of those embryos. One reason behind these observed defects may be an impaired One Carbon Metabolism (OCM) The present study was performed to test the hypothesis that Cobalamin (Vitamin B12, an important OCM co-factor) supplementation during IVM corrects DNA methylation of IVP embryos and, consequently, ameliorates placental vasculogenesis...
April 15, 2017: Theriogenology
https://www.readbyqxmd.com/read/28255022/molecular-features-of-early-onset-adult-myelodysplastic-syndrome
#18
Cassandra M Hirsch, Bartlomiej P Przychodzen, Tomas Radivoyevitch, Bhumika Patel, Swapna Thota, Michael J Clemente, Yasunobu Nagata, Thomas LaFramboise, Hetty Carraway, Aziz Nazha, Mikkael A Sekeres, Hideki Makishima, Jaroslaw P Maciejewski
Myelodysplastic syndromes are typically diseases of older adults. Early onset patients may have distinct molecular and clinical features or reflect a demographic continuum. The identification of differences between early onset patients and those diagnosed at a traditional age has the potential to advance understanding of the pathogenesis of myelodysplasia and may lead to formation of distinct morphologic subcategories. We studied a cohort of 634 patients with various subcategories of myelodysplastic syndrome and secondary acute myeloid leukemia, stratifying based on age at presentation and clinical parameters...
March 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28252641/mechanical-compression-induces-vegfa-overexpression-in-breast-cancer-via-dnmt3a-dependent-mir-9-downregulation
#19
Baek Gil Kim, Ming-Qing Gao, Suki Kang, Yoon Pyo Choi, Joo Hyun Lee, Ji Eun Kim, Hyun Ho Han, Seong Gyeong Mun, Nam Hoon Cho
Tumor growth generates mechanical compression, which may trigger mechanotransduction in cancer and stromal cells and promote tumor progression. However, very little is known about how compression stimulates signal transduction and contributes to tumor progression. In the present study, we demonstrated that compression enhances a tumor progression phenotype using an in vitro compression model, and validated the results from the in vitro model with high- and low-compressed breast cancer tissues. Mechanical compression induced miR-9 downregulation by DNMT3A-dependent promoter methylation in the MDA-MB-231 and BT-474 breast cancer cell lines and in cancer-associated fibroblasts...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28251343/methyl-donor-depletion-of-head-and-neck-cancer-cells-in-vitro-establishes-a-less-aggressive-tumour-cell-phenotype
#20
Vanessa Hearnden, Hilary J Powers, Abeir Elmogassabi, Rosanna Lowe, Craig Murdoch
PURPOSE: DNA methylation plays a fundamental role in the epigenetic control of carcinogenesis and is, in part, influenced by the availability of methyl donors obtained from the diet. In this study, we developed an in-vitro model to investigate whether methyl donor depletion affects the phenotype and gene expression in head and neck squamous cell carcinoma (HNSCC) cells. METHODS: HNSCC cell lines (UD-SCC2 and UPCI-SCC72) were cultured in medium deficient in methionine, folate, and choline or methyl donor complete medium...
March 1, 2017: European Journal of Nutrition
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