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Epigenetics pathology

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https://www.readbyqxmd.com/read/28735484/microsphere-based-assessment-of-dna-methylation-for-aml-prognosis
#1
Gerald B W Wertheim, Marlise R Luskin, Martin Carroll, Stephen R Master
Epigenetic dysregulation, including aberrant methylation of cytosine residues in DNA, is a hallmark of cancer and clearly results in oncogenic cellular alterations such as transcriptional attenuation of tumor suppressors and genomic instability. A number of studies have examined DNA methylation alterations in patients with acute myeloid leukemia (AML) and have shown that analysis of multilocus methylation patterns can identify biologically distinct AML subclasses and can predict patient prognosis. In order to utilize the prognostic capability of methylation analysis in a clinical setting, we have developed a microsphere-based HpaII tiny fragment enrichment by ligation-mediated PCR (xMELP) assay to interrogate the methylation state of genomic multiple loci along with a random forest-based classification algorithm that correlates DNA methylation status with patient prognosis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28725914/vascular-complications-in-diabetes-old-messages-new-thoughts
#2
REVIEW
Josephine M Forbes, Amelia K Fotheringham
In parallel with the growing diabetes pandemic, there is an increasing burden of micro- and macrovascular complications, occurring in the majority of patients. The identification of a number of synergistic accelerators of disease, providing therapeutic pathways, has stabilised the incidence of complications in most western nations. However, the primary instigators of diabetic complications and, thus, prevention strategies, remain elusive. This has necessitated a refocus on natural history studies, where tissue and plasma samples are sequentially taken to determine when and how disease initiates...
July 19, 2017: Diabetologia
https://www.readbyqxmd.com/read/28723648/cytosine-5-hydroxymethylation-regulates-vhl-gene-expression-in-renal-clear-cell-carcinoma
#3
En-Guang Ma, Yu-Feng Bai, Wei Cao, Yan Cao, Yong-Gang Huang, Huan-Chen Cheng, Rui-Hua An
Cytosine5-hyxymethylation (5hmC)which is a new epigenetic modification form plays important roles in the development and progression of tumors. In the present study, we observed that levels of 5hmC in the promoter region of Von Hippel-Lindau (VHL) were lower in 97 samples of renal clear cell carcinoma tissue than in matched adjacent benign tissues. Moreover, when the cancer tissue samples were divided based on pathological staging, VHL expression and the level of 5hmC in the VHL promoter were both lower in pathological grade III tumors than in grades I or II...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723469/inflammation-microbiota-and-prostate-cancer
#4
REVIEW
Martin Puhr, Angelo De Marzo, William Isaacs, Marshall Scott Lucia, Karen Sfanos, Srinivasan Yegnasubramanian, Zoran Culig
CONTEXT: Chronic inflammation of the prostate has been associated with preneoplastic lesions and cancer development. Multiple causes have been considered for chronic inflammation of the prostate. Inflammatory cytokines such as interleukins are implicated in prostate carcinogenesis and development. OBJECTIVE: To evaluate literature published on etiological factors, urinary microbiota, morphological features of proliferative inflammatory atrophy and high-grade prostate intraepithelial neoplasia, genetic polymorphisms, inflammatory stress, and cytokine signaling...
October 2016: European Urology Focus
https://www.readbyqxmd.com/read/28721198/brd4-inhibition-for-the-treatment-of-pathological-organ-fibrosis
#5
REVIEW
Matthew S Stratton, Saptarsi M Haldar, Timothy A McKinsey
Fibrosis is defined as excess deposition of extracellular matrix, resulting in tissue scarring and organ dysfunction. It is estimated that 45% of deaths in the developed world are due to fibrosis-induced organ failure. Despite the well-accepted role of fibrosis in the pathogenesis of numerous diseases, there are only two US Food and Drug Administration-approved anti-fibrotic therapies, both of which are currently restricted to the treatment of pulmonary fibrosis. Thus, organ fibrosis represents a massive unmet medical need...
2017: F1000Research
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#6
Rocío Simón, Carolina J Simoes da Silva, Sol Fereres, Ana Busturia
The Polycomb group (PcG) of proteins control developmental gene silencing and are highly conserved between flies and mammals. PcG proteins function by controlling post-translational modification of histones, such as ubiquitylation, which impacts chromatin compaction and thus gene transcription. Changes in PcG cellular levels have drastic effects on organismal development and are involved in the generation of human pathologies such as cancer. However, the mechanisms controlling their levels of expression and their physiological effects are only partially understood...
July 13, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28710355/high-resolution-imaging-of-dna-methylation-dynamics-using-a-zebrafish-reporter
#7
Ranran Zhang, Lian Liu, Yuxiao Yao, Fei Fei, Feng Wang, Qian Yang, Yonghao Gui, Xu Wang
As one of the major epigenetic modifications, DNA methylation is constantly regulated during embryonic development, cell lineage commitment, and pathological processes. To facilitate real-time observation of DNA methylation, we generated a transgenic zebrafish reporter of DNA methylation (zebraRDM) via knockin of an mCherry-fused methyl-CpG binding domain (MBD) probe driven by the bactin2 promoter. The probe colocalized with heterochromatin, and its intensity was positively correlated with 5 mC immunostaining at a subcellular resolution in early embryos...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709638/dna-methylation-protects-against-cisplatin-induced-kidney-injury-by-regulating-specific-genes-including-interferon-regulatory-factor-8
#8
Chunyuan Guo, Lirong Pei, Xiao Xiao, Qingqing Wei, Jian-Kang Chen, Han-Fei Ding, Shuang Huang, Guoping Fan, Huidong Shi, Zheng Dong
DNA methylation is an epigenetic mechanism that regulates gene transcription without changing primary nucleotide sequences. In mammals, DNA methylation involves the covalent addition of a methyl group to the 5-carbon position of cytosine by DNA methyltransferases (DNMTs). The change of DNA methylation and its pathological role in acute kidney injury (AKI) remain largely unknown. Here, we analyzed genome-wide DNA methylation during cisplatin-induced AKI by reduced representation bisulfite sequencing. This technique identified 215 differentially methylated regions between the kidneys of control and cisplatin-treated animals...
July 11, 2017: Kidney International
https://www.readbyqxmd.com/read/28707092/the-determinants-of-alternative-rna-splicing-in-human-cells
#9
REVIEW
Tatsiana V Ramanouskaya, Vasily V Grinev
Alternative splicing represents an important level of the regulation of gene function in eukaryotic organisms. It plays a critical role in virtually every biological process within an organism, including regulation of cell division and cell death, differentiation of tissues in the embryo and the adult organism, as well as in cellular response to diverse environmental factors. In turn, studies of the last decade have shown that alternative splicing itself is controlled by different mechanisms. Unfortunately, there is no clear understanding of how these diverse mechanisms, or determinants, regulate and constrain the set of alternative RNA species produced from any particular gene in every cell of the human body...
July 13, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28706445/histone-demethylase-kdm2b-upregulates-histone-methyltransferase-ezh2-expression-and-contributes-to-the-progression-of-ovarian-cancer-in-vitro-and-in-vivo
#10
Yan Kuang, Fangfang Lu, Jianfeng Guo, Hong Xu, Qi Wang, Chaohuan Xu, Longjia Zeng, Suyi Yi
Aberrant histone methylation contributes to the progression and development of many tumors. Histone methylation is a dynamic process regulated by both histone demethylase and histone methyltransferase, which ultimately alters the levels of gene transcription. However, the relationship between histone demethylase and histone methyltransferase, as well as their regulatory mechanisms in ovarian cancer development, is still unclear. Lysine-specific demethylase 2B (KDM2B) is a key demethylase of H3K36me3 and H3K4me3 that regulates gene expression and plays a role in tumorigenesis via epigenetic mechanisms...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28705657/role-of-glutathione-in-the-regulation-of-epigenetic-mechanisms-in-disease
#11
REVIEW
José Luis García-Giménez, Carlos Romá-Mateo, Gisselle Pérez-Machado, Lorena Peiró-Chova, Federico V Pallardó
Epigenetics is a rapidly growing field that studies gene expression modifications not involving changes in the DNA sequence. Histone H3, one of the basic proteins in the nucleosomes that make up chromatin, is S-glutathionylated in mammalian cells and tissues, making Gamma-L-glutamyl-L-cysteinylglycine, glutathione (GSH), a physiological antioxidant and second messenger in cells, a new post-translational modifier of the histone code that alters the structure of the nucleosome. However, the role of GSH in the epigenetic mechanisms likely goes beyond a mere structural function...
July 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28704777/preinvasive-disease-of-the-airway
#12
REVIEW
Ricky M Thakrar, Adam Pennycuick, Elaine Borg, Sam M Janes
Squamous cell carcinoma of the lung arises from preinvasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, not every lesion appears to follow this course and many individuals can have stable disease, or indeed regress to normal epithelium. From our increased understanding of the molecular pathology it is becoming apparent that the respiratory epithelium accumulates progressive genetic and epigenetic insults in response to carcinogens...
July 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28702092/pat-h-ms-coupled-with-laser-microdissection-to-study-histone-post-translational-modifications-in-selected-cell-populations-from-pathology-samples
#13
Roberta Noberini, Rémi Longuespée, Cristina Richichi, Giancarlo Pruneri, Mark Kriegsmann, Giuliana Pelicci, Tiziana Bonaldi
BACKGROUND: Aberrations in histone post-translational modifications (hPTMs) have been linked with various pathologies, including cancer, and could not only represent useful biomarkers but also suggest possible targetable epigenetic mechanisms. We have recently developed an approach, termed pathology tissue analysis of histones by mass spectrometry (PAT-H-MS), that allows performing a comprehensive and quantitative analysis of histone PTMs from formalin-fixed paraffin-embedded pathology samples...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28701587/prostate-cancer-diagnosis-using-epigenetic-biomarkers-3d-high-content-imaging-and-probabilistic-cell-by-cell-classifiers
#14
Darko Stefanovski, George Tang, Kolja Wawrowsky, Raymond C Boston, Nils Lambrecht, Jian Tajbakhsh
BACKGROUND: Prostate cancer (PCa) management can benefit from novel concepts/biomarkers for reducing the current 20-30% chance of false-negative diagnosis with standard histopathology of biopsied tissue. METHOD: We explored the potential of selected epigenetic markers in combination with validated histopathological markers, 3D high-content imaging, cell-by-cell analysis, and probabilistic classification in generating novel detailed maps of biomarker heterogeneity in patient tissues, and PCa diagnosis...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700589/ank1-is-up-regulated-in-laser-captured-microglia-in-alzheimer-s-brain-the-importance-of-addressing-cellular-heterogeneity
#15
Diego Mastroeni, Shobana Sekar, Jennifer Nolz, Elaine Delvaux, Katie Lunnon, Jonathan Mill, Winnie S Liang, Paul D Coleman
Recent epigenetic association studies have identified a new gene, ANK1, in the pathogenesis of Alzheimer's disease (AD). Although strong associations were observed, brain homogenates were used to generate the data, introducing complications because of the range of cell types analyzed. In order to address the issue of cellular heterogeneity in homogenate samples we isolated microglial, astrocytes and neurons by laser capture microdissection from CA1 of hippocampus in the same individuals with a clinical and pathological diagnosis of AD and matched control cases...
2017: PloS One
https://www.readbyqxmd.com/read/28698407/ccctc-binding-factor-inhibits-breast-cancer-cell-proliferation-and-metastasis-via-inactivation-of-the-nuclear-factor-kappab-pathway
#16
Jie Wu, Peng-Chang Li, Jun-Yi Pang, Guo-You Liu, Xue-Min Xie, Jia-Yao Li, Yi-Cong Yin, Jian-Hua Han, Xiu-Zhi Guo, Ling Qiu
CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698163/selective-effect-of-hydroxyapatite-nanoparticles-on-osteoporotic-and-healthy-bone-formation-correlates-with-intracellular-calcium-homeostasis-regulation
#17
Rui Zhao, Pengfei Xie, Kun Zhang, Zhurong Tang, Xuening Chen, Xiangdong Zhu, Yujiang Fan, Xiao Yang, Xingdong Zhang
Adequate bone substitutes osseointegration has been difficult to achieve in osteoporosis. Hydroxyapatite of the osteoporotic bone, secreted by pathologic osteoblasts, had a smaller crystal size and lower crystallinity than that of the normal. To date, little is known regarding the interaction of synthetic hydroxyapatite nanoparticles (HANPs) with osteoblasts born in bone rarefaction. The present study investigated the biological effects of HANPs on osteoblastic cells derived from osteoporotic rat bone (OVX-OB), in comparison with the healthy ones (SHM-OB)...
July 8, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28698146/epigenetic-regulation-of-epithelial-mesenchymal-transition-by-kdm6a-histone-demethylase-in-lung-cancer-cells
#18
Minoru Terashima, Akihiko Ishimura, Sasithorn Wanna-Udom, Takeshi Suzuki
Histone methylation is associated with various biological and pathological processes including cancer development. KDM6A is a candidate tumor suppressor gene that encodes a histone H3 lysine 27 (H3K27) demethylase. In this study, we discovered that ectopic expression of KDM6A antagonized TGF-β-induced epithelial-mesenchymal transition (EMT) and cell migration of lung cancer cell lines through its demethylase activity. KDM6A counteracted TGF-β-dependent changes in the expression of EMT-related genes such as CDH1/E-cadherin, FN1/Fibronectin, ZEB family and microRNA-200 family...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28695747/novel-strategies-for-anti-aging-drug-discovery
#19
Komal Saraswat, Syed Ibrahim Rizvi
Scientific achievements in the last few decades, leading to effective therapeutic interventions, have dramatically improved human life expectancy. Consequently, aging has become a significant problem and represents the major risk factor for most human pathologies including diabetes, cardiovascular diseases, neurological disorders, and cancer. Scientific discoveries over the past two decades have been instrumental in dissecting molecular mechanism(s) which play important roles in determining longevity. The same understanding has also led to the acknowledgement of the plurality of 'causes' which act either alone or in combination to create the condition which can be defined as 'aging'...
July 11, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28694462/transgenerational-inheritance-of-susceptibility-to-diabetes-induced-male-subfertility
#20
Gabriela Pavlinkova, Hasmik Margaryan, Eva Zatecka, Eliska Valaskova, Fatima Elzeinova, Alena Kubatova, Romana Bohuslavova, Jana Peknicova
Male infertility is a worldwide problem associated with genetic background, environmental factors, and diseases. One of the suspected contributing factors to male infertility is diabetes mellitus. We investigated the molecular and morphological changes in sperms and testicular tissue of diabetic males. The study was performed in streptozotocin-induced type 1 diabetes mouse model. Diabetes decreased sperm concentration and viability and increased sperm apoptosis. Changes in protamine 1/protamine 2 ratio indicated reduced sperm quality...
July 10, 2017: Scientific Reports
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