keyword
MENU ▼
Read by QxMD icon Read
search

Small molecule epigenetics

keyword
https://www.readbyqxmd.com/read/28215221/targeting-chromatin-remodeling-in-inflammation-and-fibrosis
#1
J Yang, B Tian, A R Brasier
Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28215142/small-molecule-modulation-of-hdac6-activity-the-propitious-therapeutic-strategy-to-vanquish-neurodegenerative-disorders
#2
Shabir Ahmad Ganai
Histone deacetylases (HDACs) are epigenetic enzymes creating the transcriptionally inactive state of chromatin by erasing acetyl moiety from histone and non-histone substrates. HDAC6 modulates several biological pathways in dividing cells as well as in post-mitotic neurons, and has been implicated in the pathophysiology of neurodegeneration. The distinct cellular functions and survival in these cells are reliant on HDAC6-mediated processes including intracellular trafficking, chaperone-mediated stress responses, anti-oxidation and protein degradation...
February 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28187790/retinoic-acid-and-tgf-%C3%AE-signalling-cooperate-to-overcome-mycn-induced-retinoid-resistance
#3
David J Duffy, Aleksandar Krstic, Melinda Halasz, Thomas Schwarzl, Anja Konietzny, Kristiina Iljin, Desmond G Higgins, Walter Kolch
BACKGROUND: Retinoid therapy is widely employed in clinical oncology to differentiate malignant cells into their more benign counterparts. However, certain high-risk cohorts, such as patients with MYCN-amplified neuroblastoma, are innately resistant to retinoid therapy. Therefore, we employed a precision medicine approach to globally profile the retinoid signalling response and to determine how an excess of cellular MYCN antagonises these signalling events to prevent differentiation and confer resistance...
February 10, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28184298/recent-advances-in-understanding-assessing-toxicity-to-the-epigenome
#4
REVIEW
Kevin Sweder
The ability of non-genotoxic agents to induce cancer has been documented and clearly requires a reassessment of testing for environmental and human safety. Drug safety testing has historically relied on test batteries designed to detect DNA damage leading to mutation and cancer. The standard genetic toxicology testing battery has been a reliable tool set to identify small molecules/chemicals as hazards that could lead to genetic changes in organisms and induction of cancer. While pharmaceutical companies and regulatory agencies have extensively used the standard battery, it is not suitable for compounds that may induce epigenetic changes...
2017: F1000Research
https://www.readbyqxmd.com/read/28182006/coordinate-activities-of-brd4-and-cdk9-in-the-transcriptional-elongation-complex-are-required-for-tgf%C3%AE-induced-nox4-expression-and-myofibroblast-transdifferentiation
#5
Talha Ijaz, Mohammad Jamaluddin, Yingxin Zhao, Yueqing Zhang, Jayson Jay, Celeste C Finnerty, David N Herndon, Ronald G Tilton, Allan R Brasier
Transdifferentiation of quiescent dermal fibroblasts to secretory myofibroblasts has a central role in wound healing and pathological scar formation. This myofibroblast transdifferentiation process involves TGFβ-induced de novo synthesis of alpha smooth muscle cell actin (αSMA)+ fibers that enhance contractility as well as increased expression of extracellular matrix (ECM) proteins, including collagen and fibronectin. These processes are mediated upstream by the reactive oxygen species (ROS)-producing enzyme Nox4, whose induction by TGFβ is incompletely understood...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28181261/the-search-for-potent-small-molecule-hdacis-in-cancer-treatment-a-decade-after-vorinostat
#6
REVIEW
Chiara Zagni, Giuseppe Floresta, Giulia Monciino, Antonio Rescifina
Histone deacetylases (HDACs) play a crucial role in the remodeling of chromatin, and are involved in the epigenetic regulation of gene expression. In the last decade, inhibition of HDACs came out as a target for specific epigenetic changes associated with cancer and other diseases. Until now, more than 20 HDAC inhibitors (HDACIs) have entered clinical studies, and some of them (e.g., vorinostat, romidepsin) have been approved for the treatment of cutaneous T-cell lymphoma. This review provides an overview of current knowledge, progress, and molecular mechanisms of HDACIs, covering a period from 2011 until 2015...
February 9, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28178884/improved-post-thaw-function-and-epigenetic-changes-in-mesenchymal-stromal-cells-cryopreserved-using-multicomponent-osmolyte-solutions
#7
Kathryn Pollock, Rebekah Samsonraj, Amel Dudakovic, Roman Thaler, Aron Stumbras, David McKenna, Peter Dosa, Andre van Wijnen, Allison Hubel
Current methods for freezing mesenchymal stromal cells (MSCs) result in poor post-thaw function, which limits the clinical utility of these cells. This investigation develops a novel approach to preserve MSCs using combinations of sugars, sugar alcohols and small molecule additives. MSCs frozen using these solutions exhibit improved post-thaw attachment and a more normal alignment of the actin cytoskeleton compared to cells exposed to dimethylsulfoxide (DMSO). Osteogenic and chondrogenic differentiation assays show that cells retain their mesenchymal lineage properties...
February 8, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28157484/small-molecules-modulate-chromatin-accessibility-to-promote-neurog2-mediated-fibroblast-to-neuron-reprogramming
#8
Derek K Smith, Jianjing Yang, Meng-Lu Liu, Chun-Li Zhang
Pro-neural transcription factors and small molecules can induce the reprogramming of fibroblasts into functional neurons; however, the immediate-early molecular events that catalyze this conversion have not been well defined. We previously demonstrated that neurogenin 2 (NEUROG2), forskolin (F), and dorsomorphin (D) can reprogram fibroblasts into functional neurons with high efficiency. Here, we used this model to define the genetic and epigenetic events that initiate an acquisition of neuronal identity. We demonstrate that NEUROG2 is a pioneer factor, FD enhances chromatin accessibility and H3K27 acetylation, and synergistic transcription activated by these factors is essential to successful reprogramming...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/28155868/a-critical-role-for-p38mapk-signalling-pathway-during-reprogramming-of-human-fibroblasts-to-ipscs
#9
Irina Neganova, Valeria Chichagova, Lyle Armstrong, Majlinda Lako
Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) holds enormous promise for regenerative medicine. Reprogramming is a stepwise process with well-defined stages of initiation, maturation and stabilisation which are critically dependent on interactions between key pluripotency transcription factors, epigenetic regulators and signalling pathways. In this manuscript we have investigated the role of p38 MAPK signalling pathway and have shown a subpopulation- and phase-specific pattern of activation occurring during the initiation and maturation stage of reprogramming in partially and fully reprogrammed cells respectively...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28144824/cellular-reprogramming-for-clinical-cartilage-repair
#10
REVIEW
Britta J H Driessen, Colin Logie, Lucienne A Vonk
The repair of articular cartilage needs a sufficient number of chondrocytes to replace the defect tissue, and therefore, expansion of cells is generally required. Chondrocytes derived by cellular reprogramming may provide a solution to the limitations of current (stem) cell-based therapies. In this article, two distinct approaches-induced pluripotent stem cell (iPSC)-mediated reprogramming and direct lineage conversion-are analysed and compared according to criteria that encompass the qualification of the method and the derived chondrocytes for the purpose of clinical application...
January 31, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28128194/a-molecular-roadmap-for-induced-multi-lineage-trans-differentiation-of-fibroblasts-by-chemical-combinations
#11
Xiaoping Han, Hao Yu, Daosheng Huang, Yang Xu, Assieh Saadatpour, Xia Li, Lengmei Wang, Jie Yu, Luca Pinello, Shujing Lai, Mengmeng Jiang, Xueying Tian, Fen Zhang, Yanhong Cen, Yuko Fujiwara, Wei Zhu, Bin Zhou, Tianhua Zhou, Hongwei Ouyang, Jianan Wang, Guo-Cheng Yuan, Shumin Duan, Stuart H Orkin, Guoji Guo
Recent advances have demonstrated the power of small molecules in promoting cellular reprogramming. Yet, the full potential of such chemicals in cell fate manipulation and the underlying mechanisms require further characterization. Through functional screening assays, we find that mouse embryonic fibroblast cells can be induced to trans-differentiate into a wide range of somatic lineages simultaneously by treatment with a combination of four chemicals. Genomic analysis of the process indicates activation of multi-lineage modules and relaxation of epigenetic silencing programs...
January 27, 2017: Cell Research
https://www.readbyqxmd.com/read/28123403/the-epigenome-as-a-therapeutic-target-for-parkinson-s-disease
#12
REVIEW
Shane V Hegarty, Aideen M Sullivan, Gerard W O'Keeffe
Parkinson's disease (PD) is a common, progressive neurodegenerative disease characterised by degeneration of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their effectiveness wear off over time and their prolonged use leads to disabling side-effects in PD patients. There is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in PD...
November 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28120717/understanding-epigenetic-alterations-in-alzheimer-s-and-parkinson-s-disease-towards-targeted-biomarkers-and-therapies
#13
Filippo Ciceri, David Rotllant, Tamara Maes
BACKGROUND: Alzheimer's and Parkinson's disease represent the two most common neurodegenerative disorders, affecting an increasing number of patients worldwide. Population ageing and lack of effective therapies and biomarkers strongly contribute to the socio-economical impact of these conditions. MESSAGE AND CONCLUSION: The aim of the review is to present a summary of the discoveries made on the epigenetics of Alzheimer's and Parkinson's disease, with a special focus on the recent advances towards the identification of new targeted therapies and biomarkers...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28112397/interplay-between-the-mirnome-and-the-epigenetic-machinery-implications-in-health-and-disease
#14
REVIEW
Shagun Poddar, Devesh Kesharwani, Malabika Datta
Epigenetics refers to functionally relevant genomic changes that do not involve changes in the basic nucleotide sequence. Majorly, these are of two types- DNA methylation and histone modifications. Small RNA molecules called miRNAs are often thought to mediate post-transcriptional epigenetic changes by mRNA degradation or translational attenuation. While DNA methylation and histone modifications have their own independent effects on various cellular events, several reports are suggestive of an obvious interplay between these phenomena and the miRNA regulatory program within the cell...
January 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28107481/bet-inhibitors-disrupt-rad21-dependent-conformational-control-of-kshv-latency
#15
Horng-Shen Chen, Alessandra De Leo, Zhuo Wang, Andrew Kerekovic, Robert Hills, Paul M Lieberman
Kaposi's Sarcoma-associated Herpesvirus (KSHV) establishes stable latent infection in B-lymphocytes and pleural effusion lymphomas (PELs). During latency, the viral genome persists as an epigenetically constrained episome with restricted gene expression programs. To identify epigenetic regulators of KSHV latency, we screened a focused small molecule library containing known inhibitors of epigenetic factors. We identified JQ1, a Bromodomain and Extended Terminal (BET) protein inhibitor, as a potent activator of KSHV lytic reactivation from B-cells carrying episomal KSHV...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28092669/interplay-between-epigenetics-and-metabolism-in-oncogenesis-mechanisms-and-therapeutic-approaches
#16
REVIEW
C C Wong, Y Qian, J Yu
Epigenetic and metabolic alterations in cancer cells are highly intertwined. Oncogene-driven metabolic rewiring modifies the epigenetic landscape via modulating the activities of DNA and histone modification enzymes at the metabolite level. Conversely, epigenetic mechanisms regulate the expression of metabolic genes, thereby altering the metabolome. Epigenetic-metabolomic interplay has a critical role in tumourigenesis by coordinately sustaining cell proliferation, metastasis and pluripotency. Understanding the link between epigenetics and metabolism could unravel novel molecular targets, whose intervention may lead to improvements in cancer treatment...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28080202/chemical-probes-targeting-epigenetic-proteins-applications-beyond-oncology
#17
Suzanne Ackloo, Peter J Brown, Susanne Müller
Epigenetic chemical probes are potent, cell-active, small molecule inhibitors and antagonists of specific domains in a protein; they have been indispensable for studying bromodomains and protein methyltransferases. The Structural Genomics Consortium (SGC), comprising scientists from academic and pharmaceutical laboratories, has generated most of the current epigenetic chemical probes. Moreover, the SGC has shared about four thousand aliquots of these probes, which have been used primarily for phenotypic profiling or to validate targets in cell lines or primary patient samples cultured in vitro...
January 12, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28071961/cellular-analysis-of-the-action-of-epigenetics-drugs-and-probes
#18
Mirjam Hau, Fides Zenk, A Ganesan, Nicola Iovino, Manfred Jung
Small molecule drugs and probes are important tools in drug discovery, pharmacology, and cell biology. This is of course also true for epigenetic inhibitors. Important examples for the use of established epigenetic inhibitors are the study of the mechanistic role of a certain target in a cellular setting or the modulation of a certain phenotype in an approach that aims towards therapeutic application. Alternatively, cellular testing may aim at the validation of a new epigenetic inhibitor in drug discovery approaches...
January 10, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28069948/genomic-targeting-of-epigenetic-probes-using-a-chemically-tailored-cas9-system
#19
Glen P Liszczak, Zachary Z Brown, Samuel H Kim, Rob C Oslund, Yael David, Tom W Muir
Recent advances in the field of programmable DNA-binding proteins have led to the development of facile methods for genomic localization of genetically encodable entities. Despite the extensive utility of these tools, locus-specific delivery of synthetic molecules remains limited by a lack of adequate technologies. Here we combine the flexibility of chemical synthesis with the specificity of a programmable DNA-binding protein by using protein trans-splicing to ligate synthetic elements to a nuclease-deficient Cas9 (dCas9) in vitro and subsequently deliver the dCas9 cargo to live cells...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28038447/proteome-alterations-associated-with-transformation-of-multiple-myeloma-to-secondary-plasma-cell-leukemia
#20
Alexey Zatula, Aida Dikic, Celine Mulder, Animesh Sharma, Cathrine B Vågbø, Mirta M L Sousa, Anders Waage, Geir Slupphaug
Plasma cell leukemia is a rare and aggressive plasma cell neoplasm that may either originate de novo (primary PCL) or by leukemic transformation of multiple myeloma (MM) to secondary PCL (sPCL). The prognosis of sPCL is very poor, and currently no standard treatment is available due to lack of prospective clinical studies. In an attempt to elucidate factors contributing to transformation, we have performed super-SILAC quantitative proteome profiling of malignant plasma cells collected from the same patient at both the MM and sPCL stages of the disease...
December 27, 2016: Oncotarget
keyword
keyword
27390
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"