scholarly journals Πρότυπο μεθυλίωσης σε ασθενείς με ιδιοπαθή φλεγμονώδη νόσο του εντέρου

2014 ◽  
Author(s):  
Παντελής Καρατζάς
Keyword(s):  
Peripheral Blood ◽  
Statistical Tests ◽  
Methylation Status ◽  
Methylation Profile ◽  
Healthy Individuals ◽  
Intestinal Tissue ◽  
Tissue Samples ◽  
Blood Samples ◽  
Number Of Patients ◽  
Show Evidence

Objective This thesis aimed to investigate the methylation profile of 22 genes associated with thepathogenesis of IBD in patients with ulcerative colitis (UC) or Crohn’s Disease (CD) andcompare them with the methylation profile of the same genes in healthy controls. Anadditional purpose of the study was to investigate whether methylation profile of these genesbetween inflamed intestinal tissue and peripheral blood are in concordance, hoping to indicatea possible future use of methylation as biomarker.Materials & MethodsIsolated peripheral blood samples and inflamed intestinal tissue samples were collectedfrom 24 patients with IBD, 12 of them suffering from UC and 12 from CD. The control groupconsisted of 12 healthy subjects without any personal and family history of digestive diseases.The promoter methylation status of genes involved in inflammation and autoimmunity wasprofiled using the Human Inflammatory Response and Autoimmunity EpiTect Methyl IISignature PCR Array profiles. Methylation was considered to be hyper-methylated if >20%according to the instructions of the manufacturer. The microarrays were validated with Quantitative Real-time PCR.The statistical analysis was performed using non-parametricstatistical tests (non-parametric statistical tests).ResultsRegarding CD, the methylation status of IL10RA, IL13, IL13RA1 and IL17C inperipheral blood samples did not differ significantly from the methylation status of healthycontrols. Only three genes – ATF2, CXCL5 and IL12B showed higher methylation in CDcompared to controls, but they did not exceed the threshold of 20% for hypermethylation. Allother genes tested appear lower methylation than controls.Regarding UC, methylation status of CXCL6 and IL13RA1 in peripheral blood samplesdid not differ significantly from the methylation status of healthy individuals. Five genes(CXCL14, CXCL5, GATA3, IL17C and IL4R,) were found to be significantly hypermethylatedin UC patients compared to healthy individuals. Some genes show higher methylation thancontrols, but they do not exceed 20% methylation threshold for hypermethylation. All other genes show lower methylation in UC compared to controls.Active cases of both CD and UC could be promptly distinguished from healthycontrols based on the signatures provided by the methylation profiles in peripheral bloodsamples. Based on these results - despite the relatively limited number of patients - it waspossible to define distinct signatures for active CD vs. active UC. Specifically, CXCL14,CXCL5, GATA3, IL17C and IL4R genes were hyper-methylated in UC compared to CD. Inaddition, CXCL6 which did not differ significantly between UC and controls appeared hypermethylatedcompared to CD; in contrast, IL13 which did not differ significantly between CDand controls appeared hypermethylated in CD compared to UC. Moreover the real-timequantitative PCR conducted for seven genes (CCL25, IL13, IL17RA, IL17A, IL12B, CXCL5,and IL4R) confirmed the causal relationship between hyper-methylation and lower expressionof genes. Finally, it was confirmed that methylation profile in intestinal tissue and peripheralblood are in concordance. ConclusionsIn this study we have identified panels of genes that show evidence of differentialmethylation between UC and controls, as well as CD and UC. Moreover there is strongevidence that methylation level in intestinal tissue samples is well related to methylation levelin whole blood samples. Our findings suggest that these genes play an important role in IBDpathogenesis, as differential methylation status observed affects gene expression at the mRNAlevel. In conclusion, the different methylation levels between CD and UC could play a role inconfirming the diagnosis of IBD, determining the exact type of IBD (UC or CD) and possiblyestimating the activity of disease

Azacytidine as a Maintenance Therapy in Elderly AML Progressively Demethylates CpG Sites within the p16 Gene

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4466-4466
Author(s):  
Margaret Dellett ◽  
Michelle Lazenby ◽  
Alan K Burnett ◽  
Ken I Mills
Keyword(s):  
Dna Methylation ◽  
Maintenance Therapy ◽  
Peripheral Blood ◽  
Age Of Onset ◽  
Methylation Status ◽  
Global Methylation ◽  
Cpg Sites ◽  
Number Of Patients ◽  
Elderly Aml ◽  
Diagnostic Samples

Abstract Acute myeloid leukemia (AML) accounts for ~30% of adult leukaemia cases and is expected to increase as the population ages, due to median age of onset at ~60 years old. Recent evidence suggests that DNA methylation is actively involved in AML and myelodysplastic syndrome (MDS). Tumor suppressor genes, such as p16, have been shown to be silenced by methylation in AML. However, epigenetic events such as DNA methylation are reversible and therefore targets for chemotherapeutic intervention. It has been reported that ~30% of MDS patients with an abnormal karyotype show normalization of their methylation status after receiving a demethylating drug during early stages of their therapy. The UK NCRI AML16 programme for elderly patients (>60 years old at diagnosis) with AML and high risk MDS has several therapeutic questions for patients considered fit for intensive treatment, one of which is to compare the use of azacytidine demethylation maintenance treatment with no maintenance therapy. Samples were obtained from patients entered into the AML16 trial, at diagnosis and from patients entered into the intensive arm of the trial who were randomized to receive azacytidine maintenance therapy were analyzed for the alterations for genomic methylation. Pyrosequencing was used to determine methylation within 17 CpG sites within p16, MLH1, and MGMT whilst LINE1 was used as a measure of global methylation. To date, approximately 714 patients have been entered into AML16. Of these 195 diagnostic samples have been analyzed, of which 103 were in the intensive arm of the trial. At the second randomization stage, 34 patient samples were analyzed and a further 26 samples were obtained following 3, 6 or 9 courses of azacytidine therapy. Statistical comparison of the methylation levels at each individual CpG or for the averaged CpG in each gene studies indicated that there was no difference whether the sample was derived from bone marrow or peripheral blood. This allowed the direct comparison of peripheral blood samples obtained at 2nd randomization and during azacytidine maintenance courses. Differential levels of methylation at individual CpG within the gene were seen at diagnosis. Higher levels of average p16 methylation were observed in the AML patients when compared to a small cohort of “well elderly” individuals. No difference was noted in the individual or averaged CpG methylation status for MGMT or LINE1 during the maintenance course of azacytidine. However, the methylation status of the CpG sites within the p16 and MLH1 genes reduced during maintenance by a median of 19% and 25% respectively. However, the number of patients completing three courses of azacytidine was only about 20% of those entering the intensive arm of AML16, however sequential samples from the same individual also showed demethylation of the CpG sites in p16 and MLH1. This study shows that azacytidine maintenance therapy in elderly AML patients does reduce the methylation status of some genes whilst others genes show no response. This is being investigated further using arrays containing 12,000 CpG sites which will be correlated with gene expression microarrays on the diagnostic samples from AML16.

scholarly journals Gene expression of one important microRNA in blood and tissue samples of oral squamous cell carcinoma

2021 ◽  
Author(s):  
Naghmeh Emami ◽  
Naghmeh Bahrami ◽  
Masoumeh Mirzaei ◽  
Abdolreza Mohamadnia
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Peripheral Blood ◽  
Expression Level ◽  
P Value ◽  
Healthy Individuals ◽  
Tissue Samples

Introduction: Oral Squamous Cell Carcinoma (OSCC) is one of the most common oral malignancies, which accounts for 80-90% of malignant neoplasms of the oral cavity. MicroRNAs (miRNAs) are small RNA molecules that regulate post-transcriptional gene expression by targeting mRNAs. Materials and Methods: In this case-control study, 40 patients with oral squamous cell carcinoma and 40 healthy individuals as control were studied. Blood samples were collected from both groups. Also, 30 cancer tissue samples and 30 healthy tissue samples were prepared and evaluated. RNA was extracted from collected peripheral blood and tissue samples and evaluated for the expression level of miR-494 via real-time PCR technique. P. value values<0.05 were considered statistically significant. Results: The expression level of miR-494 in serum (peripheral blood) of patients with oral squa- mous cell carcinoma increased by 1.12 fold (P-value<0.001) compared with healthy individuals. Also, the expression level of miR-494 in samples of oral squamous cell carcinoma infected tissue showed a 1.28-fold increase compared to healthy tissue. Conclusion: The results of this study indicate an increase in the expression level (up-regula- tion) of miR-494 in oral squamous cell carcinoma. This biomarker can be used in screening and early detection of oral squamous cell carcinoma.

scholarly journals DNA Methylation Status of SHOX-Flanking CpG Islands in Healthy Individuals and Short Stature Patients with Pseudoautosomal Copy Number Variations

2019 ◽  
Vol 158 (2) ◽  
pp. 56-62 ◽  
Author(s):  
Kenichiro Ogushi ◽  
Atsushi Hattori ◽  
Erina Suzuki ◽  
Hirohito Shima ◽  
Masako Izawa ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Short Stature ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Copy Number ◽  
Methylation Status ◽  
Cpg Islands ◽  
Copy Number Variations ◽  
Peripheral Blood Cells ◽  
Healthy Individuals

SHOX resides in the short arm pseudoautosomal region (PAR1) of the sex chromosomes and escapes X inactivation. SHOX haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). A substantial percentage of cases with SHOX haploinsufficiency arise from pseudoautosomal copy number variations (CNVs) involving putative enhancer regions of SHOX. Our previous study using peripheral blood samples showed that some CpG dinucleotides adjacent to SHOX exon 1 were hypomethylated in a healthy woman and methylated in a woman with gross X chromosomal rearrangements. However, it remains unknown whether submicroscopic pseudoautosomal CNVs cause aberrant DNA methylation of SHOX-flanking CpG islands. In this study, we examined the DNA methylation status of SHOX-flanking CpG islands in 50 healthy individuals and 10 ISS/LWD patients with pseudoautosomal CNVs. In silico analysis detected 3 CpG islands within the 20-kb region from the translation start site of SHOX. Pyrosequencing and bisulfite sequencing of genomic DNA samples revealed that these CpG islands were barely methylated in peripheral blood cells and cultured chondrocytes of healthy individuals, as well as in peripheral blood cells of ISS/LWD patients with pseudoautosomal CNVs. These results, in conjunction with our previous findings, indicate that the DNA methylation status of SHOX-flanking CpG islands can be affected by gross X-chromosomal abnormalities, but not by submicroscopic CNVs in PAR1. Such CNVs likely disturb SHOX expression through DNA methylation-independent mechanisms, which need to be determined in future studies.

Reduced Proteasomal Activity in Marrow Cells From Myelodysplastic Syndrome (MDS) Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1776-1776
Author(s):  
Stela Karabina ◽  
Eleni Thanopoulou ◽  
Sotirios D Athanasiou ◽  
Argiris Symeonidis ◽  
Nicholas Zoumbos
Keyword(s):  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Proteasome Activity ◽  
Healthy Individuals ◽  
Blood Samples ◽  
Proteasomal Activity ◽  
Healthy Donors ◽  
Intracellular Proteins ◽  
Blood Mononuclear Cells ◽  
Marrow Cells

Abstract Abstract 1776 Poster Board I-802 Introduction The proteasome is a multicatalytic complex that is responsible for the degradation of many intracellular proteins in the cytoplasm and nucleus of all eukaryotic cells. The chymotryptic-like (ChT-L) activity is one of the three proteasomal activities and is rate-limiting in the degradation of intracellular proteins. Such proteins include natural unfolded proteins, oxidized, mutated or damaged proteins and many short–lived proteins such as cell cycle proteins. The correlation between MDS and the presence of increased oxidative stress as well as oxidized proteins within the cell has already been reported. Insufficient proteasomal activity causes the accumulation of oxidatively modified proteins something that may lead to the misregulation of cellular homeostasis. In addition, its role to the pathogenesis of many diseases has already been documented and many studies over the past years strongly indicate the implication of proteasome in many hematological malignancies. Patients and methods: In this study we examined the proteasomal activity of mononuclear cells and immunomagnetically isolated CD34+ marrow cells from 24 marrow and 9 peripheral blood samples from MDS patients (10 RA, 2 RARS, 5 RCMD, 10 RAEB I, 2 RAEB II, 4 CMML) compared to the cells from 6 marrow samples of age matched healthy individuals, 8 mobilized peripheral blood samples (mPB) and 14 blood samples from healthy donors. For each sample, cells were lysed with Dithiothreitol (DTT) followed by incubation with the fluorescent conjugated peptide Suc-LLVY-AMC. The fluorescence intensity was directly dependent to ChT-L activity within the cells. The proteasome inhibitor MG-132 was used as negative control. We also examined the amount of the β1 subunit of the proteasome in marrow mononuclear cells from MDS patients, by flow cytometry. Results Proteasome activity was significantly reduced in MDS marrow mononuclear cells compared with the cells from healthy individuals. The reduction was 55% and 75% compared with mononuclear cells from marrow samples of healthy donors and mPB samples, respectively. The activity was similarly reduced in both CD34+ and CD34- marrow cells from MDS patients compared to the cells from healthy individuals (70% and 60% reduction respectively). Further analysis showed high variation of the amount of the β1 proteasomal subunit in MDS patients contrary to healthy individuals. Additionally, cells from the mPB samples possessed higher levels of proteasomal activity and β1 subunit compared to the cells from healthy donors. Proteasome activity of blood mononuclear cells from MDS patients was similar to the cells from the blood samples of healthy individuals although the variance was high in both study groups. Conclusions Both mononuclear and progenitor CD34+ marrow cells from MDS patients have reduced proteasomal activity compared to the same cell populations from healthy individuals. However, no difference in activity was detected between MDS and healthy individuals blood mononuclear cells. The quantitative assessment of the proteasome shows high variation within the MDS group and further investigation is required. Disclosures No relevant conflicts of interest to declare.

scholarly journals Discrimination between human populations using a small number of differentially methylated CpG sites: a preliminary study using lymphoblastoid cell lines and peripheral blood samples of European and Chinese origin

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Patrycja Daca-Roszak ◽  
Roman Jaksik ◽  
Julia Paczkowska ◽  
Michał Witt ◽  
Ewa Ziętkiewicz
Keyword(s):  
Cell Lines ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Methylation Status ◽  
Predictive Ability ◽  
Human Populations ◽  
Lymphoblastoid Cell Lines ◽  
Blood Samples ◽  
Cpg Sites ◽  
Lymphocyte Cell

Abstract Background Epigenetics is one of the factors shaping natural variability observed among human populations. A small proportion of heritable inter-population differences are observed in the context of both the genome-wide methylation level and the methylation status of individual CpG sites. It has been demonstrated that a limited number of carefully selected differentially methylated sites may allow discrimination between main human populations. However, most of the few published results have been performed exclusively on B-lymphocyte cell lines. Results The goal of our study was to identify a set of CpG sites sufficient to discriminate between populations of European and Chinese ancestry based on the difference in the DNA methylation profile not only in cell lines but also in primary cell samples. The preliminary selection of CpG sites differentially methylated in these two populations (pop-CpGs) was based on the analysis of two groups of commercially available ethnically-specific B-lymphocyte cell lines, performed using Illumina Infinium Human Methylation 450 BeadChip Array. A subset of 10 pop-CpGs characterized by the best differentiating criteria (|Mdiff| > 1, q < 0.05; lack of the confounding genomic features), and 10 additional CpGs in their immediate vicinity, were further tested using pyrosequencing technology in both B-lymphocyte cell lines and in the primary samples of the peripheral blood representing two analyzed populations. To assess the population-discriminating potential of the selected set of CpGs (further referred to as “composite pop (CEU-CHB)-CpG marker”), three classification methods were applied. The predictive ability of the composite 8-site pop (CEU-CHB)-CpG marker was assessed using 10-fold cross-validation method on two independent sets of samples. Conclusions Our results showed that less than 10 pop-CpG sites may distinguish populations of European and Chinese ancestry; importantly, this small composite pop-CpG marker performs well in both lymphoblastoid cell lines and in non-homogenous blood samples regardless of a gender.

scholarly journals Discrimination between human populations using a small number of differentially methylated CpG sites:  A preliminary study using lymphoblastoid cell lines and peripheral blood samples of European and Chinese origin.

2020 ◽  
Author(s):  
Patrycja Daca-Roszak ◽  
Roman Jaksik ◽  
Julia Paczkowska ◽  
Michal Witt ◽  
Ewa Zietkiewicz
Keyword(s):  
Cell Lines ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Methylation Status ◽  
Human Populations ◽  
Lymphoblastoid Cell Lines ◽  
Blood Samples ◽  
Chinese Populations ◽  
Cpg Sites ◽  
Lymphocyte Cell

Abstract Background Epigenetics is one of the factors shaping natural variability observed among human populations. A small proportion of heritable inter-population differences are observed in the context of both the genome-wide methylation level and the methylation status of individual CpG sites. It has been demonstrated that a limited number of carefully selected differentially methylated sites may allow discrimination between main human populations. However, most of the few published results have been performed exclusively on B-lymphocyte cell lines. Results The goal of our study was to identify a set of CpG sites sufficient to discriminate between European and Chinese populations based on the difference in the DNA methylation profile not only in cell lines but also in primary cell samples. The preliminary selection of CpG sites differentially methylated in these two populations (pop-CpGs) was based on the analysis of two groups of commercially available ethnically-specific B-lymphocyte cell lines, performed using Illumina Infinium Human Methylation 450 BeadChip Array. A subset of ten pop-CpGs characterized by the best differentiating criteria (|Mdiff|>1, q<0.05; lack of the confounding genomic features), and ten additional CpGs in their immediate vicinity, were further tested using pyrosequencing technology in both B-lymphocyte cell lines and in the primary samples of the peripheral blood representing two analyzed populations. To assess the population-discriminating potential of the selected set of CpGs (further referred to as “ composite pop(CEU-CHB)-CpG marker ”) , three classification methods were applied. The predictive ability of the composite 8-site pop(CEU-CHB)-CpG marker was assessed using 10-fold cross-validation method on two independent sets of samples. Conclusions Our results showed that less than 10 pop-CpG sites may distinguish European and Chinese populations; importantly, this small composite pop-CpG marker performs well in both lymphoblastoid cell lines and in non-homogenous blood samples regardless of a gender .

scholarly journals Telomere Length in Cystic Fibrosis Patients – Are Patients with CF Ageing Too Quickly?

2021 ◽  
pp. 90
Author(s):  
Keyword(s):  
Cystic Fibrosis ◽  
Telomere Length ◽  
Peripheral Blood ◽  
Demographic Data ◽  
Repetitive Sequences ◽  
Annual Review ◽  
Healthy Population ◽  
Healthy Individuals ◽  
Blood Samples ◽  
Biological Ageing

Life expectancy for patients living with Cystic Fibrosis (CF) is increasing year on year and there is growing interest in the ageing process in CF. Telomeres are repetitive sequences of DNA that cap the ends of eukaryotic chromosomes and shorten with ongoing cell division, thus providing a marker of replicative history and biological ageing. We aimed to investigate whether telomere length as a function of age differs between patients with CF and healthy individuals and whether telomere length is associated with severity of the patient’s CF condition. Peripheral blood samples and demographic data were collected from 47 consenting patients (age 1 to 57 years) with CF attending their routine annual review appointment at the All Wales Adult CF Centre and Noah’s Ark Children’s’ Hospital in Cardiff, UK. Telomere length profiles were assessed from peripheral blood samples, using the high resolution single telomere length analysis technique (STELA) and compared to healthy control telomere length data. Patients with CF had significantly shorter telomere lengths than healthy individuals, when adjusting for age (p<0.001). Telomere length is decreasing 70% more quickly in the CF cohort than healthy controls. Telomere length does not appear to correlate with markers of disease severity. Telomere lengths are significantly shorter in individuals with CF than in the age-adjusted healthy population. This is suggestive of premature biological ageing of peripheral blood leukocytes in CF patients.

No Evidence for t(14;18)-Positive Cells in Newborns and Young Children until the Age of 10 Followed by a Linear Increase of the Prevalence in Healthy Individuals until the Age of 50 Years.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4281-4281
Author(s):  
Frank Schüler ◽  
Lars Dölken ◽  
Sandra Dölken ◽  
Carsten Hirt ◽  
Gerhard Fusch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Peripheral Blood ◽  
Age Groups ◽  
Lymphoid Tissues ◽  
Median Frequency ◽  
Healthy Individuals ◽  
Tissue Samples ◽  
Spleen Tissue ◽  
Tonsil Tissue

Abstract The t(14;18) translocation associated with follicular lymphoma can be detected in healthy individuals when highly sensitive PCR-based techniques are applied on blood and tissue samples. We studied the prevalence and frequency of t(14;18)-positive cells in a total of 632 healthy individuals (newborns to elderly adults). A standardized quantitative real-time PCR was carried out for the detection of t(14;18)-MBR-positive cells [Dölken,L. et al.; Biotechniques1998;25:1058–1064]. The K-ras wild-type gene served as reference gene to determine the number of cells in a given sample. The individuals under study were divided into eight age groups (A: 0–9; B: 10–19; C: 20–29; D: 30–39, E: 40–49; F: 50–59; G: 60–69; H: 70–91 years). The prevalence of t(14;18) positive cells within these ten groups strongly correlates with age (χ2 Test: P &lt; 0.0001). Until the age of 10 no individual (n=87; cord blood samples: n=36, 0–1 year: n=12; 1–9 years: n=39) had detectable circulating t(14;18)-positive cells. In the age groups between 10 to 50 years (n=336) the prevalence of circulating t(14;18)-positive cells shows a significant increase from each younger to the following older age group (Fisher’s exact test; each p value significant). The prevalence rises by a constant linear rate of 1.62% per year (r2=0.9945) beginning in a median age of 7.7 years (prevalence=1.62*[years]−7.7). We did not observe any further increase in the prevalence in individuals older than 50 years of age. The median frequencies of t(14;18) positive cells in the seven age groups from 10 – 91 years show an association with age (Kruskall Wallis test: P=0.0009). A one-by-one comparison of the seven age groups that had circulating t(14;18) positive cells (10–91 years) showed a significantly higher median frequency of t(14;18) positive cells in the two oldest age groups G (60–69yrs.) and H (70–91) than in younger groups (Mann Whitney test). Therefore, we were interested in determining the age when t(14;18) positive cells appear in different lymphoid tissues as well as peripheral blood and bone marrow. 12 tonsil samples with no pathological abnormality were obtained from 12 newborns. There were no detectable t(14;18)-positive cells in all cases. From further 11 individuals we analyzed peripheral blood, bone marrow, tonsil tissue, spleen tissue and lymph node tissue for t(14;18)-positive cells. Two individuals younger than 1 year had no detectable t(14;18)-positive cells in any tissue sample. In the remaining 9 individuals (17 – 32 years) t(14;18)-positive cells could be detected: 5+/9 spleen tissues, 5+/9 tonsil tissue, 4+/9 peripheral blood, 2+/9 lymph node tissue, 1+/9 bone marrow. The 5 positive spleen tissue samples had a significant higher frequency of t(14;18) positive cells than observed in peripheral blood and all other tissue samples. In conclusion, expanded t(14;18)-positive cell clones can be detected circulating in the peripheral blood after the age of 10 years with an increasing prevalence and frequency until the age of 50. Among various lymphoid tissues obtained from individuals in the age of 17–32 years the highest frequency of t(14;18)-positive cells can be found in the spleen.

scholarly journals DNA methylation analysis of candidate genes associated with dementia in peripheral blood

Epigenomics ◽  
2020 ◽  
Vol 12 (23) ◽  
pp. 2109-2123
Author(s):  
Peter D Fransquet ◽  
Paul Lacaze ◽  
Richard Saffery ◽  
James Phung ◽  
Emily Parker ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Candidate Genes ◽  
Effect Size ◽  
Peripheral Blood ◽  
Healthy Individuals ◽  
Methylation Analysis ◽  
Blood Samples ◽  
Gender Education ◽  
Dna Methylation Analysis

Aim: To investigate whether genes implicated in dementia pathogenesis are differently methylated in peripheral blood. Materials & methods: Participants included 160 cognitively healthy individuals aged 70+ years: 73 who were subsequently diagnosed with dementia and 87 controls matched on age, gender, education, smoking and baseline cognition. A total of 49 participants also provided blood samples at diagnosis. Blood DNA methylation of APOE, APP, BDNF, PIN1, SNCA and TOMM40 was examined. Results: A total of 56 of 299 probes were differentially methylated in dementia compared with controls and 39 probes prior to diagnosis. The greatest effect size was in APP (cg19423170, Δ-8.32%, adjusted p = 0.009 at diagnosis; cg19933173, Δ-4.18%, adjusted p < 0.0001 prediagnosis). Conclusion: Genes implicated in dementia pathogenesis show differential blood methylation in dementia, even prior to diagnosis.

scholarly journals Potential Role of Aspirin in the Prevention of Aneurysmal Subarachnoid Hemorrhage

2015 ◽  
Vol 39 (5-6) ◽  
pp. 332-342 ◽  
Author(s):  
Robert M. Starke ◽  
Nohra Chalouhi ◽  
Dale Ding ◽  
David M. Hasan
Keyword(s):  
Cerebral Aneurysm ◽  
Peripheral Blood ◽  
Cerebral Aneurysms ◽  
Aneurysm Rupture ◽  
Aspirin Therapy ◽  
Blood Samples ◽  
Aneurysm Formation ◽  
Number Of Patients ◽  
Increased Risk ◽  
Cox 2

Background: Inflammation is a key element behind the pathophysiology of cerebral aneurysm formation and rupture. Aspirin is a potent inhibitor of cyclooxygenase-2 (COX), which plays a critical role in the expression of immune modulators known to contribute to cerebral aneurysm formation and rupture. Currently, there are no pharmacological therapies for patients with cerebral aneurysms. Both endovascular and microsurgical interventions may be associated with significant morbidity and mortality. Potentially, a medical alternative that prevents aneurysm progression and rupture may be a beneficial therapy for a significant number of patients. Summary: In animal models, treatment with aspirin and genetic inactivation of COX-2 decreases aneurysm formation and rupture. Selective inhibition of COX-1 did not decrease aneurysm rupture, suggesting that selection inhibition of COX-2 may be critical in thwarting aneurysm progression. Walls of ruptured human intracranial aneurysms have higher levels of COX-2 and microsomal prostaglandin E2 synthase 1 (mPGES-1), both of which are known to be inhibited by aspirin. In a pilot study, patients undergoing microsurgical clipping had attenuated expression of COX-2, mPGES-1, and macrophages in aneurysm walls after 3 months of aspirin therapy versus those that did not receive aspirin. Additionally, in patients undergoing endovascular therapy, local circulating expression of chemokines and COX-2 were increased in blood samples taken from within aneurysm domes as compared to peripheral blood sample controls. Treatment with aspirin also resulted in decreased expression of COX-2 within leukocytes within aneurysms as compared to peripheral blood samples. Novel molecular imaging with ferumoxytol-enhanced MRI may help in the identification of patients at increased risk for aneurysm rupture and assessment of a response to aspirin therapy. Key Messages: Aspirin has been found to be a safe in patients harboring cerebral aneurysms and clinical studies provide evidence that it may decrease the overall rate of rupture. Furthermore, aspirin is an accessible and inexpensive medicine for patients who may not have access to endovascular or microsurgical treatment or for patients who are deemed low risk of aneurysm rupture, high risk for intervention, or both. Future clinical trials are indicated to determine the overall effect of aspirin on aneurysm progression and rupture. This review provides an update on the potential mechanisms and benefits of aspirin in the treatment of cerebral aneurysms.

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