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https://www.readbyqxmd.com/read/29284398/mechanisms-of-radiation-bystander-and-non-targeted-effects-implications-to-radiation-carcinogenesis-and-radiotherapy
#1
Rasoul Yahyapour, Elahe Motevaseli, Abolhasan Rezaeyan, Hamid Abdollahi, Bagher Farhood, Mohsen Cheki, Masoud Najafi, Vilmar Villa
Knowledge of radiobiology is of paramount importance to be able to grasp and have an in-depth understanding of the consequences of ionizing radiation. One of the most important effects of this physical stressor's interaction to targeted and non-targeted cells, tissues and organs is on the late effects on the development of primary and secondary cancers. Thus, an in-depth understanding of the mechanisms of radiation carcinogenesis remain to be elucidated, and some studies have demonstrated or proposed a role of non-targeted effect in excess risk of cancer incidence...
December 29, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/29241213/antibiotics-induced-obesity-a-mitochondrial-perspective
#2
Melisa J Andrade, Chinchu Jayaprakash, Smitha Bhat, Nikolaos Evangelatos, Angela Brand, Kapaettu Satyamoorthy
Antibiotics are the first line of treatment against infections and have contributed immensely to reduce the morbidity and mortality rates. Recently, extensive use of antibiotics has led to alterations of the gut microbiome, predisposition to various diseases and most importantly, increase in the emergence of antibiotic-resistant bacteria, which poses a major threat to global public health. Another major issue faced worldwide due to unregulated use of antibiotics in children as well as in adults is the influence of metabolism and body weight homeostasis, leading to obesity...
December 15, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/29221988/modulations-of-keap1-nrf2-signaling-axis-by-tiia-ameliorated-the-oxidative-stress-induced-myocardial-apoptosis
#3
Shi-Hai Yan, Ning-Wei Zhao, Zhi-Rong Geng, Jia-Yin Shen, Fu-Ming Liu, Dong Yan, Jie Zhou, Chao Nie, Cheng-Cai Huang, Zhu-Yuan Fang
Mounting evidence has strongly implicated oxidative stress in the development of cardiac dysfunction, and myocardial apoptosis contributes to the pathogenesis of heart failure. Quantitative cardiac proteomics data revealed that pressure load by TAC resulted in a significant decline in mitochondrial metabolic activity, where TIIA (Tanshinone IIA sulfonate) treatment reversed it in vivo, which might be mediated by Nrf2. In NRVMs, TIIA treatment ameliorated H2O2-induced caspase-3/9 activations through the suppression of p38 and mTOR signaling pathways, where caspase-mediated cleavage of YY1 and PARP resulted in the defects in mitochondrial biogenesis and DNA repair, and this event finally led to cardiomyocyte apoptosis...
December 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29161229/sex-and-dose-specific-effects-of-maternal-bisphenol-a-exposure-on-pancreatic-islets-of-first-and-second-generation-adult-mice-offspring
#4
Amita Bansal, Cetewayo Rashid, Frances Xin, Changhong Li, Erzsebet Polyak, Anna Duemler, Tom van der Meer, Martha Stefaniak, Sana Wajid, Nicolai Doliba, Marisa S Bartolomei, Rebecca A Simmons
BACKGROUND: Exposure to the environmental endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with the increased risk of diabetes and obesity. However, the underlying mechanisms remain unknown. We recently demonstrated that perinatal BPA exposure is associated with higher body fat, impaired glucose tolerance, and reduced insulin secretion in first- (F1) and second-generation (F2) C57BL/6J male mice offspring. OBJECTIVE: We sought to determine the multigenerational effects of maternal bisphenol A exposure on mouse pancreatic islets...
September 27, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29118760/septic-shock-and-the-aging-process-a-molecular-comparison
#5
Fabiano Pinheiro da Silva, Marcel Cerqueira César Machado
Aging is a continuous process promoted by both intrinsic and extrinsic factors that each trigger a multitude of molecular events. Increasing evidence supports a central role for inflammation in this progression. Here, we discuss how the low-grade chronic inflammation that characterizes aging is tightly interconnected with other important aspects of this process, such as DNA damage, mitochondrial dysfunction, and epigenetic changes. Similarly, inflammation also plays a critical role in many morbid conditions that affect patients who are admitted to Intensive Care...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29110598/sirt1-as-a-therapeutic-target-in-diabetic-complications
#6
Justyna Strycharz, Żaneta Rygielska, Ewa Świderska, Józef Drzewoski, Janusz Szemraj, Leszek Szmigiero, Agnieszka Śliwińska
Background SIRT1 is an epigenetic enzyme involved in histone and non-histone protein deacetylation. It acts primarily as a metabolic sensor, which responses to changing energy status by deacetylating crucial transcription factors and cofactors. In this way, SIRT1 regulates mitochondrial function and biogenesis, oxidative stress, inflammation, apoptosis and cellular senescence. Disturbance of all of these phenomena promotes the pathogenesis of diabetic complications. These disorders are inseparably connected with chronic hyperglycemia, which possesses a strong epigenetic determinant...
November 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29073779/mitochondrial-nad-nadh-redox-state-and-diabetic-cardiomyopathy
#7
Jessica M Berthiaume, Jacob G Kurdys, Danina M Muntean, Mariana G Rosca
SIGNIFICANCE: Diabetic cardiomyopathy is a frequent complication occurring even in well-controlled asymptomatic diabetic patients, and may advance to heart failure. Recent advances: The diabetic heart is characterized by a state of "metabolic rigidity" involving enhanced rates of fatty acid uptake and mitochondrial oxidation as the predominant energy source, and exhibits mitochondrial electron transport chain defects. These alterations promote redox state changes evidenced by a decreased NAD+/NADH ratio associated with an increase in acetyl-CoA/CoA ratio...
October 26, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29059699/identification-of-the-genomic-region-under-epigenetic-regulation-during-nonalcoholic-fatty-liver-disease-progression
#8
Kikuko Hotta, Takuya Kitamoto, Aya Kitamoto, Yuji Ogawa, Yasushi Honda, Takaomi Kessoku, Masato Yoneda, Kento Imajo, Wataru Tomeno, Satoru Saito, Atsushi Nakajima
AIM: The progression of nonalcoholic fatty liver disease (NAFLD) is affected by epigenetics. We performed co-methylation and differentially methylated region (DMR) analyses to identify the genomic region that is under epigenetic regulation during NAFLD progression. METHODS: We collected liver biopsy specimens from 60 Japanese patients with NAFLD and classified these into mild (fibrosis stages 0-2) or advanced (fibrosis stages 3-4) NAFLD. We performed genome-wide DNA methylation analysis and identified the differentially methylated CpGs between mild and advanced NAFLD...
October 23, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29043077/recent-advances-in-understanding-werner-syndrome
#9
REVIEW
Raghavendra A Shamanna, Deborah L Croteau, Jong-Hyuk Lee, Vilhelm A Bohr
Aging, the universal phenomenon, affects human health and is the primary risk factor for major disease pathologies. Progeroid diseases, which mimic aging at an accelerated rate, have provided cues in understanding the hallmarks of aging. Mutations in DNA repair genes as well as in telomerase subunits are known to cause progeroid syndromes. Werner syndrome (WS), which is characterized by accelerated aging, is an autosomal-recessive genetic disorder. Hallmarks that define the aging process include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication...
2017: F1000Research
https://www.readbyqxmd.com/read/29027980/the-plasticizer-bisphenol-a-perturbs-the-hepatic-epigenome-a-systems-level-analysis-of-the-mirnome
#10
Ludivine Renaud, Willian A da Silveira, E Starr Hazard, Jonathan Simpson, Silvia Falcinelli, Dongjun Chung, Oliana Carnevali, Gary Hardiman
Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs (miRNAs), are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops a disease that resembles human cancer. Using zebrafish as a systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development...
October 13, 2017: Genes
https://www.readbyqxmd.com/read/29018509/circrna_0046367-prevents-hepatoxicity-of-lipid-peroxidation-an-inhibitory-role-against-hepatic-steatosis
#11
Xing-Ya Guo, Jian-Neng Chen, Fang Sun, Yu-Qin Wang, Qin Pan, Jian-Gao Fan
Hepatic steatosis reflects the miRNA-related pathological disorder with triglyceride accumulation and lipid peroxidation, which leads to nonalcoholic steatohepatitis, liver fibrosis/cirrhosis, and even hepatocellular carcinoma. Circular RNA (circRNA)/miRNA interaction reveals a novel layer of epigenetic regulation, yet the miRNA-targeting circRNA remains uncertain in hepatic steatosis. Here, we uncover circRNA_0046367 to be endogenous modulator of miR-34a that underlies hepatic steatosis. In contrast to its expression loss during the hepatocellular steatosis in vivo and in vitro, circRNA_0046367 normalization abolished miR-34a's inhibitory effect on peroxisome proliferator-activated receptor α (PPARα) via blocking the miRNA/mRNA interaction with miRNA response elements (MREs)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29016348/parp-1-and-parp-2-activity-in-cancer-induced-cachexia-potential-therapeutic-implications
#12
Esther Barreiro, Joaquim Gea
Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia...
October 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28986361/regulating-microrna-expression-at-the-heart-of-diabetes-mellitus-and-the-mitochondrion
#13
Quincy A Hathaway, Mark V Pinti, Andrya J Durr, Shanawar Waris, Danielle L Shepherd, John M Hollander
Type 2 diabetes mellitus is a major risk factor for cardiovascular disease and mortality. Uncontrolled type 2 diabetes mellitus results in a systemic milieu of increased circulating glucose and fatty acids. The development of insulin resistance in cardiac tissue decreases cellular glucose import and enhances mitochondrial fatty acid uptake. While triacylglycerol and cytotoxic lipid species begin to accumulate in the cardiomyocyte, the energy substrate utilization ratio of free fatty acids (FFAs) to glucose changes to almost entirely FFAs...
October 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28986235/alpha-synuclein-epigenetics-mitochondria-metabolism-calcium-traffic-circadian-dysfunction-in-parkinson-s-disease-an-integrated-strategy-for-management
#14
REVIEW
Oliver T Phillipson
The motor deficits which characterise the sporadic form of Parkinson's disease arise from age-related loss of a subset of dopamine neurons in the substantia nigra. Although motor symptoms respond to dopamine replacement therapies, the underlying disease process remains. This review details some features of the progressive molecular pathology and proposes deployment of a combination of nutrients: R-lipoic acid, acetyl-l-carnitine, ubiquinol, melatonin (or receptor agonists) and vitamin D3, with the collective potential to slow progression of these features...
November 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28983101/emerging-therapies-for-idiopathic-pulmonary-fibrosis-a-progressive-age-related-disease
#15
REVIEW
Ana L Mora, Mauricio Rojas, Annie Pardo, Moises Selman
Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges...
November 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28965985/dysfunctions-of-mitochondria-in-close-association-with-strong-perturbation-of-long-noncoding-rnas-expression-in-down-syndrome
#16
Jia-Jun Qiu, Yan-Na Liu, Zhao-Rui Ren, Jing-Bin Yan
Trisomy 21 is the most common chromosomal disorder and underlies Down syndrome. Epigenetics, such as DNA methylation and post-translational histone modifications, plays a vital role in Down syndrome. However, the functions of epigenetics-related long noncoding RNAs (lncRNAs), found to have an impact on neural diseases such as Alzheimer's disease, remain unknown in Down syndrome. In this study, we analyzed the RNA sequencing data from Down syndrome-induced pluripotent stem cells (iPSCs) and normal iPSCs. A large number of lncRNAs were identified differentially expressed in Down syndrome-iPSCs...
November 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28949008/vitamin-d-deficiency-accelerates-ageing-and-age-related-diseases-a-novel-hypothesis
#17
Michael J Berridge
Ageing can occur at different rates, but what controls this variable rate is unknown. Here I have developed a hypothesis that vitamin D may act to control the rate of ageing. The basis of this hypothesis emerged from studyng the various cellular processes that control ageing. These processes such as autophagy, mitochondrial dysfunction, inflammation, oxidative stress, epigenetic changes, DNA disorders and alterations in Ca(2+) and reactive oxygen species (ROS) signalling are all known to be regulated by vitamin D...
November 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28941093/staging-in-bipolar-disorder-from-theoretical-framework-to-clinical-utility
#18
Michael Berk, Robert Post, Aswin Ratheesh, Emma Gliddon, Ajeet Singh, Eduard Vieta, Andre F Carvalho, Melanie M Ashton, Lesley Berk, Susan M Cotton, Patrick D McGorry, Brisa S Fernandes, Lakshmi N Yatham, Seetal Dodd
Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures...
October 2017: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
https://www.readbyqxmd.com/read/28865727/altered-mitochondrial-epigenetics-associated-with-subchronic-doxorubicin-cardiotoxicity
#19
André Ferreira, Teresa Cunha-Oliveira, Rui F Simões, Filipa S Carvalho, Ana Burgeiro, Kendra Nordgren, Kendall B Wallace, Paulo J Oliveira
Doxorubicin (DOX), a potent and broad-spectrum antineoplastic agent, causes an irreversible, cumulative and dose-dependent cardiomyopathy that ultimately leads to congestive heart failure. The mechanisms responsible for DOX cardiotoxicity remain poorly understood, but seem to involve mitochondrial dysfunction on several levels. Epigenetics may explain a portion of this effect. Since mitochondrial dysfunction may affect the epigenetic landscape, we hypothesize that this cardiac toxicity may result from epigenetic changes related to disruption of mitochondrial function...
September 1, 2017: Toxicology
https://www.readbyqxmd.com/read/28855114/mitochondrial-epigenetic-crosstalk-in-environmental-toxicology
#20
Caren Weinhouse
Crosstalk between the nuclear epigenome and mitochondria, both in normal physiological function and in responses to environmental toxicant exposures, is a developing sub-field of interest in environmental and molecular toxicology. The majority (∼99%) of mitochondrial proteins are encoded in the nuclear genome, so programmed communication among nuclear, cytoplasmic, and mitochondrial compartments is essential for maintaining cellular health. In this review, we will focus on correlative and mechanistic evidence for direct impacts of each system on the other, discuss demonstrated or potential crosstalk in the context of chemical insult, and highlight biological research questions for future study...
November 1, 2017: Toxicology
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