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https://www.readbyqxmd.com/read/28526543/thyroid-hormone-biosynthesis-machinery-is-altered-in-the-ischemic-myocardium-an-epigenomic-study
#1
Carolina Gil-Cayuela, Esther Roselló-LLetí, Estefanía Tarazón, Ana Ortega, Juan Sandoval, Luis Martínez-Dolz, Juan Cinca, Esther Jorge, José Ramón González-Juanatey, Francisca Lago, Miguel Rivera, Manuel Portolés
BACKGROUND: Abnormal thyroid hormone (TH) metabolism is significantly associated with impaired left ventricular (LV) function and death. Although TH was traditionally thought to be produced exclusively by the thyroid gland, an increasing number of studies report TH production in other tissues. Based on these findings, we evaluated whether the genes required for TH biosynthesis are expressed in the human heart, and whether their expression is altered in patients with ischemic cardiomyopathy (ICM) and is related to epigenetic variations...
May 11, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28523562/bioinformatics-tools-for-genome-wide-epigenetic-research
#2
Vladimir Espinosa Angarica, Antonio Del Sol
Epigenetics play a central role in the regulation of many important cellular processes, and dysregulations at the epigenetic level could be the source of serious pathologies, such as neurological disorders affecting brain development, neurodegeneration, and intellectual disability. Despite significant technological advances for epigenetic profiling, there is still a need for a systematic understanding of how epigenetics shapes cellular circuitry, and disease pathogenesis. The development of accurate computational approaches for analyzing complex epigenetic profiles is essential for disentangling the mechanisms underlying cellular development, and the intricate interaction networks determining and sensing chromatin modifications and DNA methylation to control gene expression...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523539/the-role-of-noncoding-rnas-in-neurodevelopmental-disorders-the-case-of-rett-syndrome
#3
Aida Obiols-Guardia, Sònia Guil
Current technologies have demonstrated that only a small fraction of our genes encode for protein products. The vast majority of the human transcriptome corresponds to noncoding RNA (ncRNA) of different size, localization, and expression profile. Despite the fact that a biological function remains yet to be determined for most ncRNAs, growing evidence points to their crucial regulatory roles at all stages in gene expression regulation, including transcriptional and posttranscriptional control, so that proper cell homeostasis seems to depend largely on a variety of ncRNA-mediated regulatory networks...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523112/development-of-highly-affine-and-selective-fluorinated-cannabinoid-type-2-receptor-ligands
#4
Rareş-Petru Moldovan, Kristin Hausmann, Winnie Deuther-Conrad, Peter Brust
Cannabinoid type 2 receptors (CB2 receptors) are involved in various pathological processes, and the visualization of their in vivo availability with positron emission tomography (PET) is of high interest. The study focuses on the introduction of fluorine into the structure of the highly affine and selective CB2 receptor ligand N-(adamantan-1-yl)-5-ethyl-2-methyl-1-phenyl-1H-imidazole-4-carboxamide (5). A novel series of compounds was developed by modifying (i) the adamantane-3-position, (ii) the imidazole-N-phenyl ring, and (iii) the imidazole-2-position, and the impact on the CB2 binding affinity and selectivity toward cannabinoid type 1 receptors (CB1) was evaluated...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28521327/epigenomics-pharmacoepigenomics-and-personalized-medicine-in-cervical-cancer
#5
Shama Prasada Kabekkodu, Sanjiban Chakrabarty, Supriti Ghosh, Angela Brand, Kapaettu Satyamoorthy
Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events...
May 19, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28513756/divergent-synthesis-of-biflavonoids-yields-novel-inhibitors-of-the-aggregation-of-amyloid-%C3%AE-1-42
#6
Tze Han Sum, Tze Jing Sum, Súil Collins, Warren R J D Galloway, David G Twigg, Florian Hollfelder, David R Spring
Biflavonoids are associated with a variety of biologically useful properties. However, synthetic biflavonoids are poorly explored within drug discovery. There is considerable structural diversity possible within this compound class and large regions of potentially biologically relevant biflavonoid chemical space remain untapped or underexplored. Herein, we report the development of a modular and divergent strategy towards biflavonoid derivatives which enabled the step-economical preparation of a structurally diverse collection of novel unnatural biflavonoids...
May 17, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28508328/mir-424-functions-as-a-tumor-suppressor-in-glioma-cells-and-is-down-regulated-by-dna-methylation
#7
Chen Jin, Minhong Li, Yian Ouyang, Zhigang Tan, Yugang Jiang
Glioma is one of the most lethal malignancies, and increasing reports revealed that microRNAs (miRNAs), a class of small non-coding RNAs, play a critical role in the development and pathology of human gliomas. MiR-424 has been found to be dysregulated in many different types of human cancers. However, the clinical significance and function of miR-424 in glioma remains unclear. Here, based on RTq-PCR analysis in 148 clinical specimens, we found miR-424 expression was significantly decreased in glioma tumor tissues than in adjacent non-neoplastic brain tissues, and decreased miR-424 expression was associated with glioma KPS (P = 0...
May 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28507726/adapting-tissue-engineered-in-vitro-cns-models-for-high-throughput-study-of-neurodegeneration
#8
Caitriona O'Rourke, Charlotte Lee-Reeves, Rosemary Al Drake, Grant Ww Cameron, A Jane Loughlin, James B Phillips
Neurodegenerative conditions remain difficult to treat, with the continuing failure to see therapeutic research successfully advance to clinical trials. One of the obstacles that must be overcome is to develop enhanced models of disease. Tissue engineering techniques enable us to create organised artificial central nervous system tissue that has the potential to improve the drug development process. This study presents a replicable model of neurodegenerative pathology through the use of engineered neural tissue co-cultures that can incorporate cells from various sources and allow degeneration and protection of neurons to be observed easily and measured, following exposure to neurotoxic compounds - okadaic acid and 1-methyl-4-phenylpyridinium...
January 2017: Journal of Tissue Engineering
https://www.readbyqxmd.com/read/28506355/-effects-of-adipose-derived-stem-cells-and-non-methylated-cpg-oligodeoxynucleotides-on-peripheral-blood-cd4-cd25-regulatory-t-cells-in-young-mice-with-food-allergy
#9
Xu-Lin Chen, Cheng-Zhong Zheng
OBJECTIVE: To investigate the effects of adipose-derived stem cells (ADSC) and non-methylated CpG-oligodeoxynucleotides (CpG-ODN) on the expression of peripheral blood CD4(+)CD25(+) regulatory T (Treg) cells in young mice with food allergy, as well as their immune intervention effects. METHODS: A total of 40 female BALB/c mice were randomly divided into control group, allergic group, ADSC treatment group, and CpG-ODN treatment group, with 10 mice in each group. A mouse model of food allergy was established by intraperitoneal injection and intragastric administration of ovalbumin (OVA) for sensitization and challenge...
May 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28502129/diagnostic-role-of-rassf1a-and-p16ink4a-promoter-gene-hypermethylation-in-serum-dna-of-lung-cancer-patients-clinicopathological-significance
#10
Wafaa T El-Sherif, Sohair K Sayed, Sherif H Galal, Hoda A Makhlouf, Alaa T Hassan, Hosam A Yousef
The most common inactivation mechanism of tumor suppressor genes, RASSF1A and p16INK4a, in lung cancer is hypermethylation. We detected the methylation status of RASSF1A and p16INK4a in serum of lung cancer patients using methylation-specific PCR and analyzed their clinicopathological significance. Each of RASSF1A and p16INK4a hypermethylation was detected in 31.1% cancer patients but not in benign lung lesion patients. Hypermethylation was preferentially observed in small cell lung cancer (SCLC) for RASSF1A (50%), but not for p16INK4a...
June 2016: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/28501774/tuning-of-major-signaling-networks-tgf-%C3%AE-wnt-notch-and-hedgehog-by-mirnas-in-human-stem-cells-commitment-to-different-lineages-possible-clinical-application
#11
REVIEW
Sedigheh Fekri Aval, Hajie Lotfi, Roghayeh Sheervalilou, Nosratollah Zarghami
Two distinguishing characteristics of stem cells, their continuous division in the undifferentiated state and growth into any cell types, are orchestrated by a number of cell signaling pathways. These pathways act as a niche factor in controlling variety of stem cells. The core stem cell signaling pathways include Wingless-type (Wnt), Hedgehog (HH), and Notch. Additionally, they critically regulate the self-renewal and survival of cancer stem cells. Conversely, stem cells' main properties, lineage commitment and stemness, are tightly controlled by epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulatory events...
May 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28501592/endoscopic-and-molecular-characterization-of-colorectal-sessile-serrated-adenoma-polyps-with-cytological-dysplasia
#12
Yoshihito Tanaka, Hiro-O Yamano, Eiichiro Yamamoto, Hiro-O Matushita, Hironori Aoki, Kenjiro Yoshikawa, Ryo Takagi, Eiji Harada, Michiko Nakaoka, Yuko Yoshida, Makoto Eizuka, Tamotsu Sugai, Hiromu Suzuki, Hiroshi Nakase
BACKGROUND AND AIMS: Sessile serrated adenoma/polyps (SSA/Ps), which are precursor lesions of colorectal cancer (CRC) with BRAF mutation and the CpG island methylator phenotype (CIMP), develop cytological dysplasia (CD) during the progression of colorectal tumorigenesis. In the present study, we aimed to clarify the endoscopic and molecular signatures of SSA/Ps, with and without CD. METHODS: A series of 208 serrated lesions, including 41 hyperplastic polyps (HPs), 90 SSA/Ps, 33 SSA/Ps with CD and 44 traditional serrated adenomas (TSAs), were observed and resected using magnifying endoscopy...
May 10, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28501566/dna-methylation-regulated-gene-expression-in-organ-fibrosis
#13
REVIEW
Xiangyu Zhang, Min Hu, Xing Lyu, Chun Li, Victor J Thannickal, Yan Y Sanders
DNA methylation is a major epigenetic mechanism to regulate gene expression. Epigenetic regulation, including DNA methylation, histone modifications and RNA interference, results in heritable changes in gene expression independent of alterations in DNA sequence. Epigenetic regulation often occurs in response to aging and environment stimuli, including exposures and diet. Studies have shown that DNA methylation is critical in the pathogenesis of fibrosis involving multiple organs sytems, contributing to significant morbidity and mortality...
May 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28498396/diverse-expression-patterns-and-tumorigenic-role-of-neurotensin-signaling-components-in-colorectal-cancer-cells
#14
Ji Tae Kim, Heidi L Weiss, B Mark Evers
Colorectal cancer (CRC), which is one of the most common malignancies worldwide, results from an accumulation of genetic and epigenetic modifications including DNA methylation. Neurotensin (NTS), a hormone localized to the gut and central nervous system, mediates its physiological and pathological effects, including growth stimulation for a variety of cancers, through three distinct NTS receptors (NTSRs). Most NTS functions are mediated through the high-affinity receptor NTSR1, and expression of NTSR1 is increased in many cancers including CRC...
May 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28497038/epigenetics-and-vascular-diseases-influence-of-non-coding-rnas-and-their-clinical-implications
#15
REVIEW
Leonardo Elia, Manuela Quintavalle
Epigenetics refers to heritable mechanisms able to modulate gene expression that do not involve alteration of the genomic DNA sequence. Classically, mechanisms such as DNA methylation and histone modifications were part of this classification. Today, this field of study has been expanded and includes also the large class of non-coding RNAs (ncRNAs). Indeed, with the extraordinary possibilities introduced by the next-generation sequencing approaches, our knowledge of the mammalian transcriptome has greatly improved...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28487416/the-amyloid-%C3%AE-oligomer-a%C3%AE-56-induces-specific-alterations-in-neuronal-signaling-that-lead-to-tau-phosphorylation-and-aggregation
#16
Fatou Amar, Mathew A Sherman, Travis Rush, Megan Larson, Gabriel Boyle, Liu Chang, Jürgen Götz, Alain Buisson, Sylvain E Lesné
Oligomeric forms of amyloid-forming proteins are believed to be the principal initiating bioactive species in many neurodegenerative disorders, including Alzheimer's disease (AD). Amyloid-β (Aβ) oligomers are implicated in AD-associated phosphorylation and aggregation of the microtubule-associated protein tau. To investigate the specific molecular pathways activated by different assemblies, we isolated various forms of Aβ from Tg2576 mice, which are a model for AD. We found that Aβ*56, a 56-kDa oligomer that is detected before patients develop overt signs of AD, induced specific changes in neuronal signaling...
May 9, 2017: Science Signaling
https://www.readbyqxmd.com/read/28486922/an-overview-on-screening-methods-for-lysine-specific-demethylase-1-lsd1-inhibitors
#17
Yi-Chao Zheng, Jiao Chang, Ting Zhang, Feng-Zhi Suo, Xiao-Bing Chen, Ying Liu, Bing Zhao, Bin Yu, Hong-Min Liu
BACKGROUND: In the past few years, lots of attention has been given to the identification and characterization of selective and potent inhibitors of the first identified histone demethylase LSD1, which may erase mono- and di-methylated histone 3 lysine 4 and 9. As the aberrant overexpression of LSD1 is involved in various pathological processes, especially cancer, obtaining selective and potent LSD1 inhibitors has emerged as a crucial issue in medicinal chemistry research. METHOD: Until now, several LSD1 inhibitor screening models have been established, including enzyme coupled assay, LC-MS based assay, FRET based assay...
May 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28486919/metabolic-imbalance-of-homocysteine-and-hydrogen-sulfide-in-kidney-disease
#18
O Karmin, Yaw L Siow
Homocysteine (Hcy) and hydrogen sulfide (H2S) are important molecules produced during the metabolism of sulfur-containing amino acids. Hcy metabolism is central to the supply of methyl groups that are essential for biological function. Hcy can be either regenerated to methionine or metabolized to cysteine, a precursor for glutathione synthesis. Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) play a crucial role in metabolizing Hcy to cysteine through the transsulfuration pathway. These two enzymes are also responsible for H2S generation through desulfuration reactions...
May 9, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28485587/strategic-design-of-2-2-bipyridine-derivatives-to-modulate-metal-amyloid-%C3%AE-aggregation
#19
Yonghwan Ji, Hyuck Jin Lee, Minjeong Kim, Geewoo Nam, Shin Jung C Lee, Jaeheung Cho, Cheol-Min Park, Mi Hee Lim
The complexity of Alzheimer's disease (AD) stems from the inter-relation of multiple pathological factors upon initiation and progression of the disease. To identify the involvement of metal-bound amyloid-β (metal-Aβ) aggregation in AD pathology, among the pathogenic features found in the AD-affected brain, small molecules as chemical tools capable of controlling metal-Aβ aggregation were developed. Herein, we report a new class of 2,2'-bipyridine (bpy) derivatives (1-4) rationally designed to be chemical modulators toward metal-Aβ aggregation over metal-free Aβ analogue...
May 9, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28485323/rhubarb-monomers-protect-intestinal-mucosal-barrier-in-sepsis-via-junction-proteins
#20
Lyu Wang, Yun-Liang Cui, Zhe Zhang, Zhao-Fen Lin, De-Chang Chen
BACKGROUND: Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins. METHODS: Healthy male Sprague-Dawley rats (weighing 230-250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0...
May 20, 2017: Chinese Medical Journal
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