Search results for "stone"
showing 10 items of 1137 documents
Genotoxicity testing: Comparison of the γH2AX focus assay with the alkaline and neutral comet assays
2017
Genotoxicity testing relies on the quantitative measurement of adverse effects, such as chromosome aberrations, micronuclei, and mutations, resulting from primary DNA damage. Ideally, assays will detect DNA damage and cellular responses with high sensitivity, reliability, and throughput. Several novel genotoxicity assays may fulfill these requirements, including the comet assay and the more recently developed γH2AX assay. Although they are thought to be specific for genotoxicants, a systematic comparison of the assays has not yet been undertaken. In the present study, we compare the γH2AX focus assay with the alkaline and neutral versions of the comet assay, as to their sensitivities and li…
Dual inhibitors of histone deacetylases and other cancer-related targets: A pharmacological perspective.
2020
International audience; Epigenetic enzymes histone deacetylases (HDACs) are clinically validated anticancer drug targets which have been studied intensively in the past few decades. Although several drugs have been approved in this field, they are still limited to a subset of hematological malignancies (in particular T-cell lymphomas), with therapeutic potential not fully realized and the drug-resistance occurred after a certain period of use. To maximize the therapeutic potential of these classes of anticancer drugs, and to extend their application to solid tumors, numerous combination therapies containing an HDACi and an anticancer agent from other mechanisms are currently ongoing in clin…
Mitochondrion at the Crossroad Between Nutrients and Epigenome.
2019
Epigenetic profile is the link between the regulation of nuclear gene expression and the environment. The most important factors capable of significantly affecting the cellular environment are the amount and quality of nutrients available. Mitochondria are both involved in the production of some of the molecules capable of directly affecting the epigenome and have a critical role in the conversion of nutrients into usable energy. Carbohydrate and fats are converted into ATP, acetyl-CoA, SAM, and NADH. These high-energy substrates are, in turn, capable of driving the epigenetic profile. We describe substances capable of affecting this mechanism. On the other hand, nutritional interventions c…
DNA Hypomethylation and Histone Variant macroH2A1 Synergistically Attenuate Chemotherapy-Induced Senescence to Promote Hepatocellular Carcinoma Progr…
2016
Abstract Aging is a major risk factor for progression of liver diseases to hepatocellular carcinoma (HCC). Cellular senescence contributes to age-related tissue dysfunction, but the epigenetic basis underlying drug-induced senescence remains unclear. macroH2A1, a variant of histone H2A, is a marker of senescence-associated heterochromatic foci that synergizes with DNA methylation to silence tumor-suppressor genes in human fibroblasts. In this study, we investigated the relationship between macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, and liver carcinogenesis. We found that protein levels of both macroH2A1 isoforms were increased in the livers of very elderly rodents and humans, a…
Advances in Understanding the Molecular Basis of the Mediterranean Diet Effect
2018
Posted with permission from the Annual Review of Food Science and Technology, Volume 9 by Annual Reviews, http://www.annualreviews.org. Increasingly, studies showing the protective effects of the Mediterranean diet (MedDiet) on different diseases (cardiovascular, diabetes, some cancers, and even total mortality and aging indicators) are being published. The scientific evidence level for each outcome is variable, and new studies are needed to better understand the molecular mechanisms whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases but also discussing other relat…
Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis
2016
Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates…
Oxidative stress-mediated alterations in histone post-translational modifications
2021
Abstract Epigenetic regulation of gene expression provides a finely tuned response capacity for cells when undergoing environmental changes. However, in the context of human physiology or disease, any cellular imbalance that modulates homeostasis has the potential to trigger molecular changes that result either in physiological adaptation to a new situation or pathological conditions. These effects are partly due to alterations in the functionality of epigenetic regulators, which cause long-term and often heritable changes in cell lineages. As such, free radicals resulting from unbalanced/extended oxidative stress have been proved to act as modulators of epigenetic agents, resulting in alte…
ZNF518B gene up-regulation promotes dissemination of tumour cells and is governed by epigenetic mechanisms in colorectal cancer
2019
AbstractMost of colorectal cancer CRC-related death is due to metastasis and the finding of markers for prognosis of invasiveness, constitutes an appealing challenge. Here, after analysing cDNA array containing 43 tumour and 5 normal mucosa samples, we report that the expression of the ZNF518B gene as a whole and that of its two major splicing isoforms are significantly increased in tumours. The canonical isoform was also up-regulated in a patients’ cohort containing 70 tumour and 69 adjacent tissue samples. The effects of silencing ZNF518B on the phenotype of CRC cell lines were then studied. The gene does not affect cell proliferation, but plays a significant role in cell migration and in…
Histone Deacetylase Inhibitors from Marine Invertebrates
2020
Simple Summary Histone deacetylases (HDACs) are enzymes that control gene expression and are involved in the onset of serious human pathologies, including cancer; hence, their inhibitors (HDACis) have received increased attention in recent years. It is known that marine invertebrates produce significant amounts of molecules showing active pharmacological properties and an extensive spectrum of biomedical applications. This review is focused on the description of the molecular, biochemical, and, where available, physiological aspects of marine invertebrate-derived compounds that possess HDACi properties, taking into consideration their possible utilization as treatment agents against differe…
MiasDB: A Database of Molecular Interactions Associated with Alternative Splicing of Human Pre-mRNAs.
2016
Alternative splicing (AS) is pervasive in human multi-exon genes and is a major contributor to expansion of the transcriptome and proteome diversity. The accurate recognition of alternative splice sites is regulated by information contained in networks of protein-protein and protein-RNA interactions. However, the mechanisms leading to splice site selection are not fully understood. Although numerous databases have been built to describe AS, molecular interaction databases associated with AS have only recently emerged. In this study, we present a new database, MiasDB, that provides a description of molecular interactions associated with human AS events. This database covers 938 interactions …