scholarly journals Endothelial specific PER2 at the crossroads of light elicited circadian amplitude enhancement as novel cardioprotective strategy and transcriptional regulation of HIF1A-dependent metabolic adaptation to myocardial ischemia

2019 ◽  
Author(s):  
Yoshimasa Oyama ◽  
Colleen M. Bartman ◽  
Stephanie Bonney ◽  
J. Scott Lee ◽  
Lori A. Walker ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Healthy Volunteers ◽  
Affinity Purification ◽  
Critical Role ◽  
Control Point ◽  
Metabolic Adaptation ◽  
Whole Genome ◽  
Myocardial Ischemia And Reperfusion ◽  
Critical Control Point ◽  
Genome Array

ABSTRACTConsistent daylight oscillations and abundant oxygen availability are fundamental to human health. While both are connected from an evolutionary and cellular perspective, only oxygen is an established therapy in cardiovascular medicine. Here, we probe the mechanistic intersection between light-(Period 2, PER2) and oxygen-(hypoxia inducible factor, HIF1A) sensing pathways in cellular adaptation to low oxygen conditions with respect to myocardial ischemia.Using a whole genome array from daylight exposed wildtype orPer2−/−mice, an affinity purification-mass spectrometry-based proteomics screen for PER2 targets in hypoxic human endothelial cells, and targeted metabolomics from human healthy volunteers after daylight therapy, we investigated the intersection of light and hypoxia elicited pathways. Housing mice under daylight conditions prior to myocardial ischemia and reperfusion (IR)-injury, uncovered circadian PER2 amplitude enhancement as novel cardioprotective strategy, mimicking HIF1A metabolic adaptation to myocardial ischemia in a PER2 regulated manner. Whole genome array analysis from daylight exposed wildtype andPer2−/−mice or myocardial IR-injury in endothelial specific PER2 deficient mice (Per2loxP/loxP-VE-Cadherin -Cre) revealed a critical role for light elicited PER2 in maintaining the endothelial barrier function during myocardial ischemia. Mechanistic studies in human endothelia pointed towards a master transcriptional regulatory role for endothelial PER2 in metabolic reprograming to hypoxia via HIF1A, which was mimicked during normoxic PER2 stabilization. Translational investigation of light elicited pathways in human healthy volunteers found similar increases of PER2 or mimicking of HIF1A dependent metabolism. These studies identify light elicited circadian amplitude enhancement of endothelial PER2 as a novel cardioprotective strategy. Furthermore, these studies identify PER2 as critical control point of endothelial metabolic reprograming to maintain vascular integrity during myocardial IR-injury and implicate the use of daylight therapy to increase endothelial PER2 signaling as a strategy for the treatment of coronary artery disease.

A Genomic Approach to Characterize the Vulnerable Patient – a Clinical Update

2019 ◽  
Vol 4 (3) ◽  
pp. 141-144
Author(s):  
Evelin Szabó ◽  
Zsolt Parajkó ◽  
Diana Opincariu ◽  
Monica Chițu ◽  
Nóra Raț ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Ischemia ◽  
Treatment Options ◽  
Ischemic Heart ◽  
Pathophysiological Mechanism ◽  
Ischemia And Reperfusion Injury ◽  
Myocardial Ischemia And Reperfusion ◽  
Vulnerable Patient ◽  
Traditional Risk Factors ◽  
New Treatment

Abstract Atherosclerosis is the elemental precondition for any cardiovascular disease and the predominant cause of ischemic heart disease that often leads to myocardial infarction. Systemic risk factors play an important role in the starting and progression of atherosclerosis. The complexity of the disease is caused by its multifactorial origin. Besides the traditional risk factors, genetic predisposition is also a strong risk factor. Many studies have intensively researched cardioprotective drugs, which can relieve myocardial ischemia and reperfusion injury, thereby reducing infarct size. A better understanding of abnormal epigenetic pathways in the myocardial pathology may result in new treatment options. Individualized therapy based on genome sequencing is important for an effective future medical treatment. Studies based on multiomics help to better understand the pathophysiological mechanism of several diseases at a molecular level. Epigenomic, transcriptomic, proteomic, and metabolomic research may be essential in detecting the pathological phenotype of myocardial ischemia and ischemic heart failure.

A hazard analysis critical control point plan applied to the Lada vegetable production units (VPU) to ensure the safety of space grown vegetables

2011 ◽  
Author(s):  
Mary Hummerick ◽  
Jay Garland ◽  
Gail Bingham ◽  
Ray Wheeler ◽  
Shane Topham ◽  
...  
Keyword(s):  
Hazard Analysis ◽  
Control Point ◽  
Vegetable Production ◽  
Critical Control Point

In Vivo MRI Visualization of Acute Myocardial Ischemia and Reperfusion in Ferrets by the Persistent Action of the Contrast Agent Gd(BME-DTTA)

Circulation ◽  
1995 ◽  
Vol 92 (12) ◽  
pp. 3549-3559 ◽  
Author(s):  
Tamás Simor ◽  
Wen-Jang Chu ◽  
Lynne Johnson ◽  
Andras Safranko ◽  
Mark Doyle ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Contrast Agent ◽  
Acute Myocardial Ischemia ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion

scholarly journals ELAVL1 is transcriptionally activated by FOXC1 and promotes ferroptosis in myocardial ischemia/reperfusion injury by regulating autophagy

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Hui-Yong Chen ◽  
Ze-Zhou Xiao ◽  
Xiao Ling ◽  
Rong-Ning Xu ◽  
Peng Zhu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Beclin 1 ◽  
Myocardial Cells ◽  
Myocardial Ischemia And Reperfusion ◽  
Functional Roles ◽  
Cellular Iron ◽  
Luciferase Activity Assay ◽  
Myocardial Ischemia Reperfusion

Abstract Aims Myocardial ischemia is the most common form of cardiovascular disease and the leading cause of morbidity and mortality. Understanding the mechanisms is very crucial for the development of effective therapy. Therefore, this study aimed to investigate the functional roles and mechanisms by which ELAVL1 regulates myocardial ischemia and reperfusion (I/R) injury. Methods Mouse myocardial I/R model and cultured myocardial cells exposed to hypoxia/reperfusion (H/R) were used in this study. Features of ferroptosis were evidenced by LDH activity, GPx4 activity, cellular iron, ROS, LPO, and GSH levels. The expression levels of autophagy markers (Beclin-1, p62, LC3), ELAVL1 and FOXC1 were measured by qRT-PCR, immunostaining and western blot. RIP assay, biotin-pull down, ChIP and dual luciferase activity assay were employed to examine the interactions of ELAVL1/Beclin-1 mRNA and FOXC1/ELAVL1 promoter. CCK-8 assay was used to examine viability of cells. TTC staining was performed to assess the myocardial I/R injury. Results Myocardial I/R surgery induced ferroptosis and up-regulated ELAVL1 level. Knockdown of ELAVL1 decreased ferroptosis and ameliorated I/R injury. Si-ELAVL1 repressed autophagy and inhibition of autophagy by inhibitor suppressed ferroptosis and I/R injury in myocardial cells. Increase of autophagy could reverse the effects of ELAVL1 knockdown on ferroptosis and I/R injury. ELAVL1 directly bound with and stabilized Beclin-1 mRNA. Furthermore, FOXC1 bound to ELAVL1 promoter region and activated its transcription upon H/R exposure. Conclusion FOXC1 transcriptionally activated ELAVL1 may promote ferroptosis during myocardial I/R by modulating autophagy, leading to myocardial injury. Inhibition of ELAVL1-mediated autophagic ferroptosis would be a new viewpoint in the treatment of myocardial I/R injury.

scholarly journals Seaweed aquaculture: a preliminary assessment of biosecurity measures for controlling the ice-ice syndrome and pest outbreaks of a Kappaphycus farm

2021 ◽  
Author(s):  
Cicilia S. B. Kambey ◽  
Iona Campbell ◽  
Elizabeth J. Cottier-Cook ◽  
Adibi R. M. Nor ◽  
Azhar Kassim ◽  
...  
Keyword(s):  
Hazard Analysis ◽  
Kappaphycus Alvarezii ◽  
Control Point ◽  
Control Measures ◽  
Seaweed Aquaculture ◽  
Critical Control Point ◽  
Management Measures ◽  
Long Line ◽  
Pest Outbreaks ◽  
The Impact

AbstractThe application of biosecurity in seaweed aquaculture plays an important role in reducing the impact of disease and pest outbreaks. The continuous occurrence of seaweed pests including the macroalgal epiphytes, epi-endophytic filamentous algae and biofilms on Kappaphycus farms may also potentially induce further incidences of the ice-ice syndrome. In this study, on-farm biosecurity management measures were tested on the commercially grown seaweeds Kappaphycus malesianus and Kappaphycus alvarezii during peak ice-ice season at Gallam-Gallam Village, Sabah, Malaysia. The investigation was focused on preventative control measures including the early detection of the ice-ice syndrome and pests through propagule health checks, regular cleaning of the crop thallus and associated long-line ropes and monitoring of the environment. Farm procedures and practices were also assessed in terms of their biosecurity ‘risk’ using the hazard analysis and critical control point (HCCAP) approach. Observations were replicated in two different farm management systems; one system adopted routine biosecurity measures and the other had no biosecurity measures. The results showed that the ice-ice syndrome and pest outbreak was significantly decreased by 60–75% for K. malesianus and 29–71% for K. alvarezii at the farm which adopted the routine biosecurity measures compared with the no biosecurity treatment. The biosecurity measures also significantly improved growth rate and seaweed quality. The infection levels of the epi-endophyte Melanothamnus sp. contributed to the ice-ice syndrome in K. malesianus, whilst the epiphyte coverage was correlated to the ice-ice incidence in K. alvarezii. This study provides the first evidence of biosecurity management measures significantly decreasing the incidence of the ice-ice syndrome and pests on a commercial seaweed farm.

scholarly journals Food Allergen Detection Methods: A Coordinated Approach

2004 ◽  
Vol 87 (6) ◽  
pp. 1383-1390 ◽  
Author(s):  
Philip R Goodwin
Keyword(s):  
Hazard Analysis ◽  
Adult Population ◽  
Control Point ◽  
Cost Effective ◽  
Test Methods ◽  
Detection Methods ◽  
Critical Control Point ◽  
Life Threatening ◽  
Monitoring And Surveillance ◽  
Analytical Approaches

Abstract The levels (1–2%) and increasing severity of allergic responses to food in the adult population are well documented, as is the phenomenon of even higher (3–8%) and apparently increasing incidence in children, albeit that susceptibility decreases with age. Problematic foods include peanut, milk, eggs, tree nuts, and sesame, but the list is growing as awareness continues to rise. The amounts of such foods that can cause allergic reactions is difficult to gauge; however, the general consensus is that ingestion of low parts per million is sufficient to cause severe reactions in badly affected individuals. Symptoms can rapidly—within minutes—progress from minor discomfort to severe, even life-threatening anaphylactic shock in those worst affected. Given the combination of high incidence of atopy, potential severity of response, and apparently widespread instances of “hidden” allergens in the food supply, it is not surprising that this issue is increasingly subject to legislative and regulatory scrutiny. In order to assist in the control of allergen levels in foods to acceptable levels, analysts require a combination of test methods, each designed to produce accurate, timely, and cost-effective analytical information. Such information contributes significantly to Hazard Analysis Critical Control Point programs to determine food manufacturers’ risk and improves the accuracy of monitoring and surveillance by food industry, commercial, and enforcement laboratories. Analysis thereby facilitates improvements in compliance with labeling laws with concomitant reductions in risks to atopic consumers. This article describes a combination of analytical approaches to fulfill the various needs of these 3 analytical communities.

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