scholarly journals DNA methylation and retinal degenerative diseases: at the crossroad between genes and diet

2020 ◽  
Vol 53 (383) ◽  
pp. MISC1-MISC3
Author(s):  
Andrea Maugeri
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Integrated Approach ◽  
Dietary Factors ◽  
Epigenetic Mechanisms ◽  
Degenerative Diseases ◽  
Retinal Cells ◽  
Significant Difference ◽  
Retinal Degenerative Diseases ◽  
The Impact

Retinal degenerative diseases are the leading causes of blindness and low vision among working-age and older adults worldwide, with 170 and 130 million individuals suffering from age-related macular degeneration (AMD) and diabetic retinopathy, respectively. Although several studies began to show benefits from dietary interventions against retinal degenerative disease, an integrated approach is needed to understand molecular mechanisms underpinning the protective or risky effect of dietary factors. A specific area of research that elucidates mechanisms involved in gene-diet interaction is the Nutri-epigenomics, the study of the impact of diet on gene expression by modulating epigenetic mechanisms. The present research investigated the role of DNA methylation – one of the most commonly analysed epigenetic mechanisms - in the pathophysiology of retinal degenerative diseases, by exploiting a multiple integrated approach. In vitro studies initially helped us to understand how pathological features of retinal degeneration (e.g. oxidative stress, inflammation and hyperglycaemia) modulated functions of enzymes involved in the methylation of Long Interspersed Nuclear Element 1 (LINE-1) sequences in retinal cells. We also proved that some nutrients (e.g. resveratrol and curcumin) might counteract these effects and restore DNA methylation level in retinal cells under oxidative, inflammatory and high glucose conditions. We further analysed whether LINE-1 methylation level differed between patients with AMD and controls without posterior segment eye diseases. Interestingly, we noted a significant difference between the two groups, with higher LINE-1 methylation level in blood samples from AMD patients. This evidence -albeit promising for biomarker discovery- requires confirmation by further large-size prospective studies taking into account different factors. Our research, in fact, also suggested that the risk of retinal degenerative diseases derives from the combination of genetic risk variants, clinical characteristics, environmental exposures and unhealthy lifestyles, which in turn are interrelated. Thus, it would be interesting to study how the exposome -the totality of exposures individuals experience over the course of life- might induce epigenetic mechanisms able to reduce or increase the risk for retinal degenerative diseases.

scholarly journals DNA Methylation Pattern in Overweight Women under an Energy-Restricted Diet Supplemented with Fish Oil

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Cátia Lira do Amaral ◽  
Fermín I. Milagro ◽  
Rui Curi ◽  
J. Alfredo Martínez
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Weight Loss ◽  
Fish Oil ◽  
Mononuclear Cells ◽  
Energy Restriction ◽  
Dietary Factors ◽  
Epigenetic Mechanisms ◽  
Overweight Women ◽  
Fish Oil Supplementation

Dietary factors modulate gene expression and are able to alter epigenetic signatures in peripheral blood mononuclear cells (PBMC). However, there are limited studies about the effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) on the epigenetic mechanisms that regulate gene expression. This research investigates the effects ofn-3-rich fish oil supplementation on DNA methylation profile of several genes whose expression has been reported to be downregulated byn-3 PUFA in PBMC:CD36,FFAR3,CD14,PDK4, andFADS1. Young overweight women were supplemented with fish oil or control in a randomized 8-week intervention trial following a balanced diet with 30% energy restriction. Fatty acid receptorCD36decreased DNA methylation at CpG +477 due to energy restriction. Hypocaloric diet-induced weight loss also reduced the methylation percentages of CpG sites located inCD14,PDK4, andFADS1. The methylation patterns of these genes were only slightly affected by the fish oil supplementation, being the most relevant to the attenuation of the weight loss-induced decrease inCD36methylation after adjusting by baseline body weight. These results suggest that then-3 PUFA-induced changes in the expression of these genes in PBMC are not mediated by DNA methylation, although other epigenetic mechanisms cannot be discarded.

scholarly journals Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications

2021 ◽  
Vol 22 (20) ◽  
pp. 10969
Author(s):  
Daniel Desaulniers ◽  
Paule Vasseur ◽  
Abigail Jacobs ◽  
M. Cecilia Aguila ◽  
Norman Ertych ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Hazard Assessment ◽  
Integrated Approach ◽  
Epigenetic Mechanisms ◽  
Cancer Hallmarks ◽  
Cell Functions ◽  
Chemical Hazard ◽  
Chemical Carcinogenicity ◽  
Covalent Modifications

Epigenetics involves a series of mechanisms that entail histone and DNA covalent modifications and non-coding RNAs, and that collectively contribute to programing cell functions and differentiation. Epigenetic anomalies and DNA mutations are co-drivers of cellular dysfunctions, including carcinogenesis. Alterations of the epigenetic system occur in cancers whether the initial carcinogenic events are from genotoxic (GTxC) or non-genotoxic (NGTxC) carcinogens. NGTxC are not inherently DNA reactive, they do not have a unifying mode of action and as yet there are no regulatory test guidelines addressing mechanisms of NGTxC. To fil this gap, the Test Guideline Programme of the Organisation for Economic Cooperation and Development is developing a framework for an integrated approach for the testing and assessment (IATA) of NGTxC and is considering assays that address key events of cancer hallmarks. Here, with the intent of better understanding the applicability of epigenetic assays in chemical carcinogenicity assessment, we focus on DNA methylation and histone modifications and review: (1) epigenetic mechanisms contributing to carcinogenesis, (2) epigenetic mechanisms altered following exposure to arsenic, nickel, or phenobarbital in order to identify common carcinogen-specific mechanisms, (3) characteristics of a series of epigenetic assay types, and (4) epigenetic assay validation needs in the context of chemical hazard assessment. As a key component of numerous NGTxC mechanisms of action, epigenetic assays included in IATA assay combinations can contribute to improved chemical carcinogen identification for the better protection of public health.

scholarly journals The Impact of Using Educational Robot through Integrative Approach on the Achievement of Tenth-Grade Students in Trigonometry

2021 ◽  
Vol 45 (2) ◽  
pp. 200-227
Keyword(s):  
Public Schools ◽  
Integrated Approach ◽  
Modern Technology ◽  
Integrative Approach ◽  
Control Group ◽  
Validity And Reliability ◽  
Significant Difference ◽  
Tenth Grade ◽  
Educational Robot ◽  
The Impact

The study aimed at investigating the impact of using the educational robot through the integrative approach on achievement among tenth grade students in trigonometry. To achieve the aims of the study the researchers developed an academic unit adopting the integrated approach by using Educational Robot. The sample of the study consisted of (120) students of the tenth grade students in public schools in the city of Amman, divided equally into two groups: experimental and control. Achievement test in mathematics was used, which were validity and reliability was verified. The results of the study showed a statistically significant difference (α≤0.05) between the averages of the two groups experimental (which used the educational robot) and the control group (which did not use the educational robot) in mathematical achievement in favor of the experimental group. The study did not show an interaction between the use of the educational robot and the gender of the student in the mathematics achievement in the students of the tenth-grade students. In light of the study's findings, the researchers recommend using modern technology tools such as robot to teach mathematics. Keywords: Educational robot, achievement, trigonometry, integrative approach

scholarly journals Perspectives of Stem Cell–Based Therapy for Age-Related Retinal Degenerative Diseases

2017 ◽  
Vol 26 (9) ◽  
pp. 1538-1541 ◽  
Author(s):  
Vladimir Holan ◽  
Barbora Hermankova ◽  
Jan Kossl
Keyword(s):  
Stem Cell ◽  
Treatment Protocol ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Cell Type ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and glaucoma, mostly affect the elderly population and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop, or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell–based therapy that could replace diseased or missing retinal cells and support regeneration. In this respect, mesenchymal stem cells (MSCs) that can be obtained from the particular patient and used as autologous cells have turned out to be a promising stem cell type for treatment. Here we show that MSCs can differentiate into cells expressing markers of retinal cells, inhibit production of pro-inflammatory cytokines by retinal tissue, and produce a number of growth and neuroprotective factors for retinal regeneration. All of these properties make MSCs a prospective cell type for cell-based therapy of age-related retinal degenerative diseases.

scholarly journals Redefining the impact of nutrition on breast cancer incidence: is epigenetics involved?

2012 ◽  
Vol 25 (1) ◽  
pp. 68-95 ◽  
Author(s):  
Dorothy Teegarden ◽  
Isabelle Romieu ◽  
Sophie A. Lelièvre
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Methylation ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Incidence ◽  
Breast Cancer Incidence ◽  
Dietary Factors ◽  
Transcription Control ◽  
The Impact

Breast cancer incidence is rising worldwide with an increase in aggressive neoplasias in young women. Possible factors involved include lifestyle changes, notably diet that is known to make an impact on gene transcription. However, among dietary factors, there is sufficient support for only greater body weight and alcohol consumption whereas numerous studies revealing an impact of specific diets and nutrients on breast cancer risk show conflicting results. Also, little information is available from middle- and low-income countries. The diversity of gene expression profiles found in breast cancers indicates that transcription control is critical for the outcome of the disease. This suggests the need for studies on nutrients that affect epigenetic mechanisms of transcription, such as DNA methylation and post-translational modifications of histones. In the present review, a new examination of the relationship between diet and breast cancer based on transcription control is proposed in light of epidemiological, animal and clinical studies. The mechanisms underlying the impact of diets on breast cancer development and factors that impede reaching clear conclusions are discussed. Understanding the interaction between nutrition and epigenetics (gene expression control via chromatin structure) is critical in light of the influence of diet during early stages of mammary gland development on breast cancer risk, suggesting a persistent effect on gene expression as shown by the influence of certain nutrients on DNA methylation. Successful development of breast cancer prevention strategies will require appropriate models, identification of biological markers for rapid assessment of preventive interventions, and coordinated worldwide research to discern the effects of diet.

scholarly journals THU0024 METHYLATION ANALYSIS OF VITAMIN D SIGNALING PATHWAY GENES IN RHEUMATOID ARTHRITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 225.1-225
Author(s):  
E. Punceviciene ◽  
J. Gaizevska ◽  
R. Sabaliauskaite ◽  
L. Venceviciene ◽  
D. Vitkus ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Dna Methylation ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Methylation Level ◽  
Methylation Pattern ◽  
Healthy Controls ◽  
Methylation Analysis ◽  
Vitamin D Metabolism ◽  
Significant Difference

Background:Vitamin D is known for its immunomodulatory and epigenome interacting effects. Vitamin D deficiency is frequently observed in rheumatoid arthritis (RA) patients compared to healthy controls, is also named as a potential risk factor in RA ethiopatogenesis and may alter DNA methylation of certain genes [1,2]. Still, causality of vitamin D deficiency in RA patients needs to be elucidated.Objectives:The aim of the study was to evaluate relationship between DNA methylation status of vitamin D related genes (VDR,CYP24A1,CYP2R1), miRNA-155 expression, vitamin D level and its association with RA.Methods:CpG islands in promoter region of theVDR,CYP24A1,CYP2R1genes were chosen for DNA methylation analysis by means of pyrosequencing. DNA from blood mononuclear cells of 31 RA patients and 31 age and sex matched healthy controls was assessed for methylation pattern after informed consent was obtained in Vilnius university Hospital Santaros klinikos Centre of Rheumatology. For miRNA analysis quantitative reverse transcription PCR was used. Chemiluminescent microplate immunoassay was used to asses 25(OH)D serum levels.Results:25(OH)D concentrations varied from deficiency (<50 nmol/l), insufficiency (50-75 nmol/l) to normal range (≥75-100 nmol/l) in RA (mean 47.49 nmol/l; SD ± 27.93) and healthy controls (mean 57.38 nmol/l; SD ± 29.93)).CYP24A1methylation level was significantly higher in comparison toVDR(p<0.0001) andCYP2R1(p<0.0001) genes in both groups.CYP24A1hypermethylation was also observed in older subjects (p=0.012). The study demonstrated a significant positive correlation between vitamin D concentration andVDR,CYP2R1genes methylation intensity (r2=0.31, p=0.014; r2=0.25, p=0.042, respectively). However, gene methylation frequency and methylation intensity showed no significant difference between RA patients and healthy controls (VDR– 2.4vs2.6 %,CYP24A1– 16.6vs15.3 %,CYP2R1– 2.6vs2.6 %) (p>0.05). To note, miRNA-155 expression negatively correlated withCYP24A1methylation intensity (r2=-0.43, p=0.009).Conclusion:Our study identified significant associations between theVDRandCYP2R1promoter methylation and vitamin D concentration. However, no significant differences in DNA methylation pattern between RA patients and healthy controls were detected. MiR-155 expression was associated withCYP24A1methylation level, confirming its possible involvement in vitamin D metabolism. The data of our study suggests that epigenetic phenomena are significantly involved in vitamin D metabolism and may have an indirect effect on RA ethiopatogenesis.References:[1]Jeffery LE, et al. Nat Rev Rheumatol. 2016,12.4:201.[2]Fetahu IS et al. Front Physiol. 2014,5:164.Acknowledgments:This project has received funding from the Research Council of Lithuania (LMTLT), agreement No. S-MIP-17-12.Disclosure of Interests:None declared

scholarly journals Analysis of mRNA expression and DNA methylation level of RAC1 gene encoding focal adhesion molecule in endometrial and peritoneal endometriosis

2020 ◽  
pp. 43-49
Author(s):  
Irwina Eka Deraya ◽  
Andon Hestiantoro ◽  
Raden Muharam ◽  
Muhammad Lucky Marwali ◽  
Agus Surur As'adi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Focal Adhesion ◽  
Methylation Level ◽  
Promoter Hypermethylation ◽  
Mrna Expression Level ◽  
Normal Endometrium ◽  
Significant Difference ◽  
Its Gene ◽  
Peritoneal Endometriosis

Focal adhesion molecules involve in cellular migration, attachment, and play a role in endometriosis pathomechanisms. Recent studies showed that the expression of RAC1, a gene encoded focal adhesion molecule, was predominantly found in endometriosis. As gene expression may be regulated by DNA methylation. Therefore, this study aimed to analyze promoter methylation level of RAC1 gene and mRNA expression in endometrial and peritoneal endometriosis tissues. This study using 20 endometrial and 9 peritoneal tissues from the same patients and 20 normal endometrial. The DNA and RNA from samples were isolated, DNA was converted using sodium bisulfite and amplified using Methyl Specific Polymerase Chain Reaction (MSP) method. The methylation level was determined by the intensity measurement of the bands that arose in gel electrophoresis using ImageJ software, whereas mRNA expression level was measured by Reverse Transcription-quantitative PCR (RT-qPCR) method. The mRNA expression level of RAC1 gene in peritoneal endometriosis increased compared to normal endometrium, as well as compared to endometrial endometriosis, but there was no significant difference in endometrial endometriosis compared to normal. Promoter hypermethylation level of RAC1 gene in peritoneal endometriosis was significantly different compared to normal endometrium, however not significant to endometrial endometriosis. Methylation level of its gene in endometrial endometriosis shown no significant difference compared to normal. There was association between promoter hypermethylation level and its mRNA expression in endometrial endometriosis (R= 0.014; p=0.952). The elevation of mRNA expression of RAC1 gene plays a role in endometrial cell migration to peritoneum, and associated with promoter hypermethylation level of its gene.

scholarly journals Available Starch: from food process control to lower glycemic response

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Vinoy Sophie ◽  
Gautier Cesbron-Lavau ◽  
Alexandra Meynier ◽  
Aurélie Goux
Keyword(s):  
Energy Intake ◽  
Global Analysis ◽  
Dietary Factors ◽  
Starch Digestibility ◽  
Daily Energy Intake ◽  
Significant Difference ◽  
Daily Energy ◽  
The Impact ◽  
Food Processes

AbstractStarch is one of the major sources of carbohydrates (CHO) contributing to about 50–70% of the daily energy intake in human diet. Processed foods contribute to an important part of daily energy intake, especially in occidental countries. During food processing, starch undergoes dramatic changes when heated in the presence of water or high pressure. The objective of this work was to evaluate the impact of controlling food processes on starch digestibility profile in cereal-based foods and the interest of preserving starch in its native, slowly digestible, form on in vivo metabolic fate.Four different food processes were evaluated: extrusion, dry bread, soft cake and rotary-moulded biscuit. The resulting differences in gelatinization of each product translated to different SDS levels. Imaging techniques (X-ray diffraction, microtomography and electronic microscopy) were used to investigate the changes in SDS structure obtained through the different food processes. For in vivo evaluation, 12 healthy subjects were recruited and consumed a portion of 50 g of available CHOs of each product, in a crossover design. Glycemic and insulin responses were evaluated over 120 minutes in postprandial period.We showed that rotary molding technology preserved starch in its intact form and provided the highest SDS content (28g/100g) when the three other technologies (dried bread, soft cake and extrusion) led to SDS content below 3g/100 g. In addition, the lowest SDS contents are explained by a higher level of starch structure disruption which translated in a shift from crystalline structure into amorphous one. These data were linked to in vivo results. The global analysis for GI indicated that a significant difference existed among the foods’ mean GI values (p < 0.0001). Rotary product showed the lowest GI values. The soft, the dried bread had medium GI and extruded product had the highest GI with 77. The global analysis for II indicated that a significant difference existed among the foods’ mean II values (p < 0.0001), with the same order as for GI values. In addition, a portion of rotary-molded biscuit decreased significantly the glycemic peak by 1 mM compared to the 3 other products.Decrease of postprandial glycemia is a meaningful target in the prevention of metabolic diseases. This can be achieved through the modification of dietary factors such as starch digestibility.

scholarly journals Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 588
Author(s):  
Vladimir Holan ◽  
Katerina Palacka ◽  
Barbora Hermankova
Keyword(s):  
Clinical Trials ◽  
Experimental Studies ◽  
Experimental Models ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.

scholarly journals Advancement in Nanostructure-Based Tissue-Engineered Biomaterials for Retinal Degenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1005
Author(s):  
Sonali Suresh Rohiwal ◽  
Zdenka Ellederová ◽  
Taras Ardan ◽  
Jiri Klima
Keyword(s):  
Stem Cells ◽  
Retinal Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Subretinal Space ◽  
Retinal Diseases ◽  
Degenerative Diseases ◽  
Retinal Cells ◽  
Wide Range ◽  
Retinal Degenerative Diseases

The review intends to overview a wide range of nanostructured natural, synthetic and biological membrane implants for tissue engineering to help in retinal degenerative diseases. Herein, we discuss the transplantation strategies and the new development of material in combination with cells such as induced pluripotent stem cells (iPSC), mature retinal cells, adult stem cells, retinal progenitors, fetal retinal cells, or retinal pigment epithelial (RPE) sheets, etc. to be delivered into the subretinal space. Retinitis pigmentosa and age-related macular degeneration (AMD) are the most common retinal diseases resulting in vision impairment or blindness by permanent loss in photoreceptor cells. Currently, there are no therapies that can repair permanent vision loss, and the available treatments can only delay the advancement of retinal degeneration. The delivery of cell-based nanostructure scaffolds has been presented to enrich cell survival and direct cell differentiation in a range of retinal degenerative models. In this review, we sum up the research findings on different types of nanostructure scaffolds/substrate or material-based implants, with or without cells, used to deliver into the subretinal space for retinal diseases. Though, clinical and pre-clinical trials are still needed for these transplants to be used as a clinical treatment method for retinal degeneration.

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