Methylome of skeletal muscle tissue in patients with hypertension and diabetes undergoing cardiopulmonary bypass

Epigenomics ◽  
2021 ◽  
Author(s):  
Ghazal Aghagoli ◽  
Andrew Del Re ◽  
Naohiro Yano ◽  
Zhiqi Zhang ◽  
Ahmad Aboul Gheit ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Cardiopulmonary Bypass ◽  
Dna Damage Response ◽  
Bypass Surgery ◽  
Heart Surgery ◽  
Minimal Effect ◽  
Uncontrolled Diabetes ◽  
Tnf Α ◽  
Damage Response

Background: Epigenomic changes occurring during surgery have been neglected in research; diabetes and hypertension can affect the epigenome but little is known about the epigenetics of skeletal muscle (SKM). Methods: DNA methylation was profiled via Illumina MethylationEPIC arrays in SKM samples obtained at the beginning and end of heart surgery with cardiopulmonary bypass. Results: Methylation in patients with hypertension and diabetes was significantly different, more so for uncontrolled diabetes; hypertension alone produced minimal effect. The affected pathways involved IL-1, IL-12, IL-18, TNF-α, IFNγ, VEGF, NF-κB and Wnt signaling, apoptosis and DNA damage response. Significant changes occurred during surgery and included loci in the Hippo–YAP/TAZ pathway. Conclusion: Cardiopulmonary bypass surgery affects the SKM methylome, and the combination of hypertension and diabetes induces changes in the SKM epigenome in contrast to hypertension alone.

Post-operative kinetics of C-reactive protein to distinguish between bacterial infection and systemic inflammation in infants after cardiopulmonary bypass surgery: the early and the late period

2021 ◽  
pp. 1-8
Author(s):  
Hanna Renk ◽  
David Grosse ◽  
Sarah Schober ◽  
Christian Schlensak ◽  
Michael Hofbeck ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Bacterial Infection ◽  
Congenital Heart ◽  
Bypass Surgery ◽  
Heart Surgery ◽  
Congenital Heart Surgery ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Post Operative Period ◽  
Kinetics Of

Abstract Objectives: Differentiation between post-operative inflammation and bacterial infection remains an important issue in infants following congenital heart surgery. We primarily assessed kinetics and predictive value of C-reactive protein for bacterial infection in the early (days 0–4) and late (days 5–28) period after cardiopulmonary bypass surgery. Secondary objectives were frequency, type, and timing of post-operative infection related to the risk adjustment for congenital heart surgery score. Methods: This 3-year single-centre retrospective cohort study in a paediatric cardiac ICU analysed 191 infants accounting for 235 episodes of CPBP surgery. Primary outcome was kinetics of CRP in the first 28 days after CPBP surgery in infected and non-infected patients. Results: We observed 22 infectious episodes in the early and 34 in the late post-operative period. CRP kinetics in the early post-operative period did not accurately differentiate between infected and non-infected patients. In the late post-operative period, infected infants displayed significantly higher CRP values with a median of 7.91 (1.64–22.02) and 6.92 mg/dl (1.92–19.65) on days 2 and 3 compared to 4.02 (1.99–15.9) and 3.72 mg/dl (1.08–9.72) in the non-infection group. Combining CRP on days 2 and 3 after suspicion of infection revealed a cut-off of 9.47 mg/L with an acceptable predictive accuracy of 76%. Conclusions: In neonates and infants, CRP kinetics is not useful to predict infection in the first 72 hours after CPBP surgery due to the inflammatory response. However, in the late post-operative period, CRP is a valuable adjunctive diagnostic test in conjunction with clinical presentation and microbiological diagnostics.

scholarly journals DNA Methylation Inhibitor 5-Aza-2′-Deoxycytidine Induces Reversible Genome-Wide DNA Damage That Is Distinctly Influenced by DNA Methyltransferases 1 and 3B

2007 ◽  
Vol 28 (2) ◽  
pp. 752-771 ◽  
Author(s):  
Stela S. Palii ◽  
Beth O. Van Emburgh ◽  
Umesh T. Sankpal ◽  
Kevin D. Brown ◽  
Keith D. Robertson
Keyword(s):  
Dna Methylation ◽  
Dna Damage ◽  
Tumor Cells ◽  
Dna Damage Response ◽  
Dna Methyltransferases ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Checkpoint Kinase ◽  
Genome Wide ◽  
Damage Response

ABSTRACT Genome-wide DNA methylation patterns are frequently deregulated in cancer. There is considerable interest in targeting the methylation machinery in tumor cells using nucleoside analogs of cytosine, such as 5-aza-2′-deoxycytidine (5-azadC). 5-azadC exerts its antitumor effects by reactivation of aberrantly hypermethylated growth regulatory genes and cytoxicity resulting from DNA damage. We sought to better characterize the DNA damage response of tumor cells to 5-azadC and the role of DNA methyltransferases 1 and 3B (DNMT1 and DNMT3B, respectively) in modulating this process. We demonstrate that 5-azadC treatment results in growth inhibition and G2 arrest—hallmarks of a DNA damage response. 5-azadC treatment led to formation of DNA double-strand breaks, as monitored by formation of γ-H2AX foci and comet assay, in an ATM (ataxia-telangiectasia mutated)-dependent manner, and this damage was repaired following drug removal. Further analysis revealed activation of key strand break repair proteins including ATM, ATR (ATM-Rad3-related), checkpoint kinase 1 (CHK1), BRCA1, NBS1, and RAD51 by Western blotting and immunofluorescence. Significantly, DNMT1-deficient cells demonstrated profound defects in these responses, including complete lack of γ-H2AX induction and blunted p53 and CHK1 activation, while DNMT3B-deficient cells generally showed mild defects. We identified a novel interaction between DNMT1 and checkpoint kinase CHK1 and showed that the defective damage response in DNMT1-deficient cells is at least in part due to altered CHK1 subcellular localization. This study therefore greatly enhances our understanding of the mechanisms underlying 5-azadC cytotoxicity and reveals novel functions for DNMT1 as a component of the cellular response to DNA damage, which may help optimize patient responses to this agent in the future.

DNA methylation changes induced by BDE-209 are related to DNA damage response and germ cell development in GC-2spd

2021 ◽  
Vol 109 ◽  
pp. 161-170
Author(s):  
Xiangyang Li ◽  
Yue Zhang ◽  
Xiaomin Dong ◽  
Guiqing Zhou ◽  
Yujian Sang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Damage ◽  
Germ Cell ◽  
Dna Damage Response ◽  
Cell Development ◽  
Germ Cell Development ◽  
Damage Response ◽  
Bde 209

“Beyond Beating Heart Surgery” Heartstring Device Protects against Perioperative Neurological Events

2010 ◽  
Vol 5 (2) ◽  
pp. 118-121 ◽  
Author(s):  
Andreas G. Sakopoulos ◽  
John G. Jacobson ◽  
Don R. Wilson ◽  
Wilfred M. Huse
Keyword(s):  
Cardiopulmonary Bypass ◽  
Coronary Artery ◽  
Coronary Artery Bypass ◽  
Coronary Artery Bypass Surgery ◽  
Bypass Surgery ◽  
Heart Surgery ◽  
Artery Bypass ◽  
Myocardial Revascularization ◽  
Off Pump ◽  
Mammary Arteries

Objective There is a growing body of evidence favoring off-pump coronary artery bypass surgery (OPCAB) over traditional coronary artery bypass surgery (CABG) with cardiopulmonary bypass as a method for reducing perioperative neurologic events. Aortic manipulation, whether with OPCAB or coronary artery bypass surgery with cardiopulmonary bypass, is strongly linked with adverse neurologic outcomes. Although the aortic “no-touch” technique has merit, most cardiac surgeons are reluctant to base entire myocardial revascularization exclusively on mammary pedicles. The purpose of this study was to analyze our experience with OPCAB combined with the use of a Heartstring proximal anastomotic device, as a strategy for reducing clinically evident cerebrovascular accidents. Methods Two hundred twenty-seven consecutive isolated OPCAB were performed without the use of a side-biting aortic clamp. In all these operations, a Heartstring device was used, permitting clampless hand-sutured proximal anastomoses. All patients were managed in this fashion regardless of the status of their ascending aorta. A mean of 3.4 bypasses were performed during each operation, with one or two mammary arteries harvested routinely. In 98% of patients, a single proximal anastomosis was performed; there was liberal use of sequential bypass grafts. Results Mean age was 69.3 years, with 17% octogenarians. Preexisting cerebrovascular disease was present in 22.4% of patients. There were no clinically evident perioperative neurologic events in any patients. There were no operative deaths. Conclusions This series suggests that OPCAB performed with a single, clampless, proximal aortic anastomosis, and with a Heartstring device may protect against perioperative strokes.

Successful Treatment of Accidental Air Embolism in Warm Heart Surgery

2003 ◽  
Vol 11 (1) ◽  
pp. 68-69 ◽  
Author(s):  
Walter J Gomes ◽  
David A Strisiver ◽  
Albert JF Penco ◽  
Kamal Rampersad ◽  
Gianni D Angelini
Keyword(s):  
Cardiopulmonary Bypass ◽  
Cerebral Perfusion ◽  
Coronary Artery Bypass Surgery ◽  
Bypass Surgery ◽  
Heart Surgery ◽  
Artery Bypass ◽  
Air Embolism ◽  
Induced Hypothermia ◽  
Retrograde Cerebral Perfusion ◽  
Warm Heart Surgery

Normothermic cardiopulmonary bypass has recently been proposed as a superior technique for maintaining body metabolism. However, its use remains controversial since the degree of cerebral protection provided might be inferior to that conferred by conventional hypothermic techniques. We report a case of accidental massive air embolism during coronary artery bypass surgery under normothermia, which was successfully managed with induced hypothermia at 20°C and retrograde cerebral perfusion.

scholarly journals Novel epigenetic signature of DNA damage response genes for prognostication and immunophenotype of non-G-CIMP glioblastomas

2021 ◽  
Author(s):  
Bowen Li ◽  
Fangfang Liu ◽  
Weihong Hu ◽  
Rui Li ◽  
Amandine Etcheverry ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Risk Score ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Close Correlation ◽  
Lower Grade ◽  
Mgmt Methylation ◽  
Damage Response

Abstract Background Dysregulation and dysfunction of DNA damage response (DDR) have prognostic and predictive implications for glioblastomas (GBMs) without glioma-CpGs island methylator phenotype (G-CIMP); mathematical modeling based on DNA methylation abnormality in DDR genes may serve as clinically useful biomarkers. Methods Independent cohorts of non-G-CIMP GBMs and IDH wild type (wt) lower-grade gliomas (LGGs) from local and public databases were included for discovery and validation of a multimarker signature, combined using a RISK score model. Different bioinformatic and functional experiments were performed for biological validation. Results By analyzing DNA methylation microarray data of DDR genes, we totally identified five CpGs, each of which was significantly correlated with overall survival (OS) of non-G-CIMP GBMs, independent of age, treatments and the O-6-methylguanine-DNA methyltransferase (MGMT) methylation status. A RISK score signature of the 5 CpGs was constructed and validated to powerfully and independently prognosticate prognosis in non-G-CIMP GBMs. It also showed good discriminating value in stratified cohorts by patient age and MGMT methylation status. Bioinformatic analysis revealed a close correlation of the DDR epigenetic signature to distinct immunophenotypes of non-G-CIMP GBMs. Functional studies showed that NSUN5, epigenetically regulated by one identified CpGs, exhibited tumor-suppressor characteristics but may have immunosuppressive implications and confer TMZ resistance to GBM cells. Conclusions The epigenetic signature of DDR genes might be of promising value for refining current prognostic classification of non-G-CIMP GBMs, and its potential links to distinct immunophenotypes make it a promising biomarker candidate in the coming era of cancer immunotherapy.

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