15,098 results match your criteria demethylation

Whole Genomic DNA Methylation Profiling of CpG Sites in Promoter Regions of Dorsal Root Ganglion in Diabetic Neuropathic Pain Mice.

J Mol Neurosci 2021 May 5. Epub 2021 May 5.

Department of Neurobiology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, 100069, Beijing, China.

DNA methylation and demethylation play an important role in neuropathic pain. In general, DNA methylation of CpG sites in the promoter region impedes gene expression, whereas DNA demethylation contributes to gene expression. Here, we evaluated the methylation status of CpG sites in genomic DNA promoter regions in dorsal root ganglions (DRGs) of diabetic neuropathic pain (DNP) mice. Read More

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Activation-induced deaminase is critical for the establishment of DNA methylation patterns prior to the germinal center reaction.

Nucleic Acids Res 2021 May 5. Epub 2021 May 5.

Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), 08916 Badalona, Barcelona, Spain.

Activation-induced deaminase (AID) initiates antibody diversification in germinal center B cells by deaminating cytosines, leading to somatic hypermutation and class-switch recombination. Loss-of-function mutations in AID lead to hyper-IgM syndrome type 2 (HIGM2), a rare human primary antibody deficiency. AID-mediated deamination has been proposed as leading to active demethylation of 5-methycytosines in the DNA, although evidence both supports and casts doubt on such a role. Read More

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Isolation and expansion of thymus-derived regulatory T cells for use in paediatric heart transplant patients.

Eur J Immunol 2021 May 5. Epub 2021 May 5.

MRC Centre for Transplantation, School of Immunology and Microbial Sciences, King's, College London, Guy's Hospital, London, UK.

Regulatory T-cells (Tregs) are a subset of T-cells generated in the thymus with intrinsic immunosuppressive properties. Phase I clinical trials have shown safety and feasibility of Treg infusion to promote immune tolerance and new studies are ongoing to evaluate their efficacy. During heart transplantation, thymic tissue is routinely discarded providing an attractive source of Tregs. Read More

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Locus-specific characterization of human endogenous retrovirus expression in prostate, breast, and colon cancers.

Cancer Res 2021 May 3. Epub 2021 May 3.

Computational Biology Institute, George Washington University

Human endogenous retroviruses (HERV) have been implicated in a variety of diseases including cancers. Recent research implicates HERVs in epigenetic gene regulation. Here we utilize a recently developed bioinformatics tool for identifying HERV expression at the locus-specific level to identify differential expression of HERVs in matched tumor-normal RNA-seq data from The Cancer Genome Atlas (TCGA). Read More

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The epigenetic regulation of synaptic genes contributes to the etiology of autism.

Rev Neurosci 2021 May 3. Epub 2021 May 3.

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05Bratislava, Slovakia.

Epigenetic mechanisms greatly affect the developing brain, as well as the maturation of synapses with pervasive, long-lasting consequences on behavior in adults. Substantial evidence exists that implicates dysregulation of epigenetic mechanisms in the etiology of neurodevelopmental disorders. Therefore, this review explains the role of enzymes involved in DNA methylation and demethylation in neurodevelopment by emphasizing changes of synaptic genes and proteins. Read More

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Nonalcoholic Fatty Liver Disease Development in Zebrafish upon Exposure to Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate, a Novel Brominated Flame Retardant.

Environ Sci Technol 2021 May 2. Epub 2021 May 2.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardant, can potentially cause lipid metabolism disorder; however, its biological effects on lipid homeostasis remain unknown. We investigated its ability to cause nonalcoholic fatty liver disease (NAFLD) in zebrafish. Female zebrafish were fed a high-fat diet (HFD, 24% crude fat) or normal diet (ND, 6% crude fat), and exposed to TBPH (0. Read More

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SIRT1 Deacetylates TET2 and Promotes Its Ubiquitination Degradation to Achieve Neuroprotection Against Parkinson's Disease.

Front Neurol 2021 15;12:652882. Epub 2021 Apr 15.

Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The epigenetic modifications, such as DNA methylation and histone acetylation, play a critical role in the pathogenesis of Parkinson's disease (PD). However, the relationship between DNA methylation and histone acetylation in PD is not fully understood. Previous studies have shown that patients with PD exhibit an epigenetic and transcriptional upregulation of Ten-Eleven Translocation 2 (TET2), a member of the DNA hydroxylases family. Read More

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Different Pharmacokinetics of Tramadol, -Demethyltramadol and -Demethyltramadol in Postoperative Surgical Patients From Those Observed in Medical Patients.

Front Pharmacol 2021 15;12:656748. Epub 2021 Apr 15.

Department of Anesthesiology, Resuscitation and ICU, Osijek University Hospital, Osijek, Croatia.

Most studies examining tramadol metabolism have been carried out in non-surgical patients and with oral tramadol. The aim of this study was 1) to measure concentrations of tramadol, -demethyltramadol (ODT), and -demethyltramadol (NDT) in the surgical patients admitted to the intensive care unit (ICU) within the first 24 postoperative hours after intravenous application of tramadol, and 2) to examine the effect of systemic inflammation on tramadol metabolism and postoperative pain. A prospective observational study was carried out in the surgical ICU in the tertiary hospital. Read More

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Pharmacokinetics of Anthraquinones from Medicinal Plants.

Front Pharmacol 2021 15;12:638993. Epub 2021 Apr 15.

Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.

Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Read More

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Pharmacokinetics, Bioavailability, Excretion and Metabolism Studies of Akebia Saponin D in Rats: Causes of the Ultra-Low Oral Bioavailability and Metabolic Pathway.

Front Pharmacol 2021 15;12:621003. Epub 2021 Apr 15.

Pharmacy Department of Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Akebia saponin D (ASD) has a variety of biological activities and great medicinal potential, but its oral bioavailability is so low as to limit its development. Its pharmacokinetic profiles and excretion and metabolism have not been fully elucidated. This study was an attempt in this area. Read More

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Mechanism of validamycin A inhibiting DON biosynthesis and synergizing with DMI fungicides against Fusarium graminearum.

Mol Plant Pathol 2021 May 2. Epub 2021 May 2.

College of Plant Protection, Nanjing Agricultural University, Nanjing, China.

Deoxynivalenol (DON) is a vital virulence factor of Fusarium graminearum, which causes Fusarium head blight (FHB). We recently found that validamycin A (VMA), an aminoglycoside antibiotic, can be used to control FHB and inhibit DON contamination, but its molecular mechanism is still unclear. In this study, we found that both neutral and acid trehalase (FgNTH and FgATH) are the targets of VMA in F. Read More

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ALKBH5-mediated m6A demethylation of lncRNA RMRP plays an oncogenic role in lung adenocarcinoma.

Hui Yu Zhe Zhang

Mamm Genome 2021 May 1. Epub 2021 May 1.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, 138 Yi xue yuan Road, Shanghai, 200032, People's Republic of China.

Lung adenocarcinomas are more common in non-smoking males and females. In this study, we investigated the function of long non-coding RNA RMRP in lung adenocarcinoma and further explore the regulatory role of ALKBH5 in lncRNA methylation. The results showed lncRNA RMRP expression was significantly enhanced in lung adenocarcinoma tissues, and is positively correlated with poor prognosis. Read More

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The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls.

Psychoneuroendocrinology 2021 Mar 23;128:105205. Epub 2021 Mar 23.

Clinic for Psychiatry, Clinical Centre of Serbia, Pasterova 2, Belgrade 11000, Serbia; Faculty of Medicine, University of Belgrade, Dr Subotica 8, Belgrade 11000, Serbia.

Hypothalamic-pituitary-adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. Read More

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Higher Cd-accumulating oilseed rape has stronger Cd tolerance due to stronger Cd fixation in pectin and hemicellulose and higher Cd chelation.

Environ Pollut 2021 Apr 24;285:117218. Epub 2021 Apr 24.

Southern Regional Collaborative Innovation Center for Grain and Oil Crops in China, College of Resources and Environmental Sciences, Hunan Agricultural University, Changsha, China. Electronic address:

Oilseed rape (Brassica napus) has potential as a hyperaccumulator in the phytoremediation of cadmium (Cd)-contaminated soils. Oilseed rape varieties with higher Cd accumulation ability and Cd tolerance are ideal candidates for the hyperaccumulation of excess Cd. To explore the physiological and molecular mechanisms underlying Cd tolerance and high Cd accumulation in oilseed rape leaves, we examined two genotypes, "BN067" (Cd-sensitive with lower Cd accumulation in leaves) and "BN06" (Cd-tolerant with higher Cd accumulation in leaves). Read More

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Methylation status of ADAM12 promoter are associated with its expression levels in colorectal cancer.

Pathol Res Pract 2021 Apr 15;221:153449. Epub 2021 Apr 15.

Department of Pathology and Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. Electronic address:

Background: Colorectal cancer (CRC) is a kind of malignant tumor of digestive system severely affecting human health. The occurrence of CRC is a polygenic and multi-step complex process involving genetic and epigenetic alterations. ADAM12 (a disintegrin and metalloproteases 12), is a gene that was commonly hypermethylated in esophageal cancer using whole-genome methylation microarray in our previous study. Read More

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Mechanism of MicroRNA-375 Promoter Methylation in Promoting Ovarian Cancer Cell Malignancy.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033820980115

Obstetrics and Gynecology Department, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.

Objective: Ovarian cancer (OC) ranks one of the most prevalent fatal tumors of female genital organs. Aberrant promoter methylation triggers changes of microRNA (miR)-375 in OC. Our study aimed to evaluate the mechanism of methylated miR-375 promoter region in OC cell malignancy and to seek the possible treatment for OC. Read More

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Characterization of in vitro phase I metabolites of methamnetamine in human liver microsomes by liquid chromatography-quadrupole time-of-flight mass spectrometry.

Int J Legal Med 2021 Apr 29. Epub 2021 Apr 29.

Pharmacological Research Division, Toxicological and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi, 28159, Chungccheongbuk-do, Republic of Korea.

N-Methyl-1-(naphthalen-2-yl)propan-2-amine (methamnetamine, PAL-1046) is an amphetamine-based new psychoactive substance (NPS). Methamnetamine has been reported to cause excessive release of serotonin, and it is classified as an empathogen or entactogen. It is not regulated as a controlled substance in most countries, and there are no studies on its metabolism. Read More

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Small-Molecule Inhibitors of the RNA M6A Demethylases FTO Potently Support the Survival of Dopamine Neurons.

Int J Mol Sci 2021 Apr 26;22(9). Epub 2021 Apr 26.

Institute of Chemistry, University of Tartu, Ravila 14a, 50411 Tartu, Estonia.

The fat mass and obesity-associated protein (FTO), an RNA N-methyladenosine (mA) demethylase, is an important regulator of central nervous system development, neuronal signaling and disease. We present here the target-tailored development and biological characterization of small-molecule inhibitors of FTO. The active compounds were identified using high-throughput molecular docking and molecular dynamics screening of the ZINC compound library. Read More

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DNA Methylation of the Angiotensinogen Gene, , and the Aldosterone Synthase Gene, in Cardiovascular Diseases.

Int J Mol Sci 2021 Apr 27;22(9). Epub 2021 Apr 27.

Department of Endocrinology and Metabolism, Kanazawa University Hospital, Kanazawa 920-8641, Japan.

Angiotensinogen (AGT) and aldosterone play key roles in the regulation of blood pressure and are implicated in the pathogenesis of cardiovascular diseases. DNA methylation typically acts to repress gene transcription. The aldosterone synthase gene is regulated by angiotensin II and potassium. Read More

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Genomic Uracil and Aberrant Profile of Demethylation Intermediates in Epigenetics and Hematologic Malignancies.

Int J Mol Sci 2021 Apr 19;22(8). Epub 2021 Apr 19.

Department of Clinical and Molecular Medicine, NTNU Norwegian University of Science and Technology, NO-7491 Trondheim, Norway.

DNA of all living cells undergoes continuous structural and chemical alterations resulting from fundamental cellular metabolic processes and reactivity of normal cellular metabolites and constituents. Examples include enzymatically oxidized bases, aberrantly methylated bases, and deaminated bases, the latter largely uracil from deaminated cytosine. In addition, the non-canonical DNA base uracil may result from misincorporated dUMP. Read More

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Stability of Imprinting and Differentiation Capacity in Naïve Human Cells Induced by Chemical Inhibition of CDK8 and CDK19.

Cells 2021 Apr 12;10(4). Epub 2021 Apr 12.

Cellular Plasticity and Disease Group, Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.

Pluripotent stem cells can be stabilized in vitro at different developmental states by the use of specific chemicals and soluble factors. The naïve and primed states are the best characterized pluripotency states. Naïve pluripotent stem cells (PSCs) correspond to the early pre-implantation blastocyst and, in mice, constitute the optimal starting state for subsequent developmental applications. Read More

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Long Non-Coding Expression Correlates with Renal Cell Carcinoma Metastasis and Aggressiveness.

Noncoding RNA 2021 Apr 10;7(2). Epub 2021 Apr 10.

Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia.

Long non-coding RNAs (lncRNAs) can be specifically expressed in different tissues and cancers. By controlling the gene expression at the transcriptional and translational levels, lncRNAs have been reported to be involved in tumor growth and metastasis. Recent data demonstrated that multiple lncRNAs have a crucial role in renal cell carcinoma (RCC) progression-the most common malignant urogenital tumor. Read More

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The JMJ29 Protein Controls Circadian Oscillation through Diurnal Histone Demethylation at the and Loci.

Genes (Basel) 2021 Apr 5;12(4). Epub 2021 Apr 5.

Department of Chemistry, Seoul National University, Seoul 08826, Korea.

The circadian clock matches various biological processes to diurnal environmental cycles, such as light and temperature. Accumulating evidence shows that chromatin modification is crucial for robust circadian oscillation in plants, although chromatin modifiers involved in regulating core clock gene expression have been limitedly investigated. Here, we report that the Jumonji C domain-containing histone demethylase JMJ29, which belongs to the JHDM2/KDM3 group, shapes rhythmic changes in H3K4me3 histone marks at core clock loci in . Read More

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Ten-eleven translocase: key regulator of the methylation landscape in cancer.

J Cancer Res Clin Oncol 2021 Apr 28. Epub 2021 Apr 28.

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India.

Purpose: Methylation of 5th residue of cytosine in CpG island forms 5-methylcytosine which is stable, heritable epigenetic mark. Methylation levels are broadly governed by methyltransferases and demethylases. An aberration in the demethylation process contributes to the silencing of gene expression. Read More

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Circular RNA circZbtb20 maintains ILC3 homeostasis and function via Alkbh5-dependent mA demethylation of Nr4a1 mRNA.

Cell Mol Immunol 2021 Apr 28. Epub 2021 Apr 28.

Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Group 3 innate lymphoid cells (ILC3s) play critical roles in innate immunity and gut homeostasis. However, how ILC3 homeostasis is regulated remains elusive. Here, we identified a novel circular RNA, circZbtb20, that is highly expressed in ILC3s and required for their maintenance and function. Read More

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Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance.

Cell Metab 2021 Apr 21. Epub 2021 Apr 21.

Department of Basic Medical Sciences, School of Medicine, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, THU-PKU Center for Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:

The ever-increasing understanding of the complexity of factors and regulatory layers that contribute to immune evasion facilitates the development of immunotherapies. However, the diversity of malignant tumors limits many known mechanisms in specific genetic and epigenetic contexts, manifesting the need to discover general driver genes. Here, we have identified the mA demethylase FTO as an essential epitranscriptomic regulator utilized by tumors to escape immune surveillance through regulation of glycolytic metabolism. Read More

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Orthogonal Demethylase-Activated Deoxyribozyme for Intracellular Imaging and Gene Regulation.

J Am Chem Soc 2021 Apr 27. Epub 2021 Apr 27.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.

The epigenetic modification of nucleic acids represents a versatile approach for achieving high-efficient control over gene expression and transcription and could dramatically expand their biosensing and therapeutic applications. Demethylase-involved removal of N6-methyladenine (mA) represents one of the vital epigenetic reprogramming events, yet its direct intracellular evaluation and as-guided gene regulation are extremely rare. The endonuclease-mimicking deoxyribozyme (DNAzyme) is a catalytically active DNA that enables the site-specific cleavage of the RNA substrate, and several strategies have imparted the magnificent responsiveness to DNAzyme by using chemical and light stimuli. Read More

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Bidirectional interaction of nobiletin and gut microbiota in mice fed with a high-fat diet.

Food Funct 2021 Apr;12(8):3516-3526

Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, New Jersey 08901, USA.

Nobiletin is abundant in citrus peels and demonstrates good anti-obesity bioactivity. However, its anti-obesity mechanisms still remain unclear. This study aims to explore the bidirectional interaction between nobiletin and gut microbiota in mice fed with a high-fat diet. Read More

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Saikosaponin D exhibits anti-leukemic activity by targeting FTO/mA signaling.

Theranostics 2021 31;11(12):5831-5846. Epub 2021 Mar 31.

Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130017, China.

The implementation of targeted therapies for acute myeloid leukemia (AML) has been challenging. Fat mass and obesity associated protein (FTO), an mRNA N-methyladenosine (mA) demethylase, functions as an oncogene that promotes leukemic oncogene-mediated cell transformation and leukemogenesis. Here, we investigated the role of Saikosaponin-d (SsD) in broad anti-proliferation effects in AML and evaluated the mA demethylation activity by targeting FTO of SsD. Read More

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The occurrence of lupus nephritis is regulated by USP7-mediated JMJD3 stabilization.

Immunol Lett 2021 Apr 22. Epub 2021 Apr 22.

Department of Dermatology, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha 410000, P.R. China. Electronic address:

Ubiquitin-specific peptidases7 (USP7) participates in the regulation of various metabolic and immune disorders. However, the role of USP7 in lupus nephritis (LN) remains unknown. The current study set out to elucidate the regulatory role of USP7 in LN together with JMJD3 and NF-κB. Read More

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