Glutathione peroxidase activity and expression levels are significantly increased in acute coronary syndromes

2017 ◽  
Vol 65 (5) ◽  
pp. 919-925 ◽  
Author(s):  
Ana Holley ◽  
Janet Pitman ◽  
John Miller ◽  
Scott Harding ◽  
Peter Larsen
Keyword(s):  
Glutathione Peroxidase ◽  
Acute Coronary Syndromes ◽  
Stable Coronary Artery Disease ◽  
Density Lipoprotein ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Protein Levels ◽  
Coronary Syndromes ◽  
Stable Cad ◽  
Gpx Activity

High levels of the antioxidant enzyme, glutathione peroxidase (GPx), have been associated with improved outcomes following acute coronary syndromes (ACS), suggesting a protective role. How GPx levels are altered with coronary disease is not clearly established. This study examined GPx activity, protein, and mRNA levels in healthy controls, patients with stable coronary artery disease (CAD), and patients with ACS. We studied 20 individuals from each of the healthy control, stable CAD, and ACS groups. GPx activity and protein levels, along with oxidized low-density lipoprotein (oxLDL) were assayed in plasma. GPx mRNA levels from whole blood were quantified using real-time PCR. Levels of GPx activity in the plasma were higher in ACS (109±7.7 U/mL) compared with patients with stable CAD (95.2±16.4 U/mL, p<0.01) and healthy controls (87.6±8.3 U/mL, p<0.001). Plasma GPx protein levels were also elevated in ACS (21.6±9.5 µg/mL) compared with patients with stable CAD (16.5±2.8 µg/mL, p<0.05) and healthy controls (16.3±5.3 µg/mL, p<0.05). Levels ofGPX1,GPX3, andGPX4mRNA were significantly higher in the patients with ACS. Levels of oxLDL were also significantly higher in patients with ACS (61.9±22.2 U/L) than in patients with stable CAD (47.8±10.4 U/L, p<0.05) and healthy controls (48.9±11.9 U/L, p<0.05). Levels of oxLDL, GPx activity, protein, and mRNA are all significantly higher in patients with ACS compared with patients with stable CAD and healthy controls. These findings suggest that GPx may be upregulated in response to a change in oxidative stress during an ACS.

scholarly journals Glutathione peroxidase in acute coronary syndromes

2021 ◽  
Author(s):  
◽  
Ana Simone Holley
Keyword(s):  
Oxidative Stress ◽  
Glutathione Peroxidase ◽  
Coronary Disease ◽  
Healthy Subjects ◽  
Acute Coronary Syndromes ◽  
Mrna Levels ◽  
Sod Activity ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
Gpx Activity

<p>Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are among the primary antioxidant enzymes that scavenge reactive oxygen species in the blood (ROS), thereby protecting against high levels of oxidative stress. The consequences of oxidative stress include cellular injury and tissue damage. High levels of oxidative stress have been implicated in the pathogenesis of acute coronary syndromes (ACS), however large clinical trials involving dietary antioxidant supplements have not shown a reduction in the rate of major adverse cardiovascular events (MACE).  In a cohort of 262 ACS patients we examined the relationship between GPx activity, SOD activity and MACE. Patients with MACE were found to have significantly lower levels of GPx activity than those without MACE, whereas SOD activity did not differ between the groups. Furthermore, dividing the patients into quartiles corresponding to levels of GPx activity demonstrated significantly higher rates of MACE in the lower quartile of GPx activity compared to the highest quartile.  Previous studies have demonstrated that deficiencies in GPx activity are associated with vascular dysfunction and platelet-dependent thrombosis, leading to the hypothesis that low levels of GPx activity would be associated with increased levels of platelet reactivity. In 51 ACS patients we did not observe a significant relationship between these two parameters, however we did demonstrate that increasing levels of GPx activity was associated with lower levels of ROS. ROS measures were based on the response of the platelets to addition of exogenous nitric oxide. Such an inverse relationship between GPx activity and levels of ROS is consistent with the view that GPx activity may play an important role in an ACS by reducing ROS-mediated damage, thereby protecting against MACE.  We examined levels of GPx activity, protein concentration and mRNA expression across populations of ACS patients, stable coronary disease patients and healthy subjects. Cardiovascular risk factors thought to influence levels of GPx activity were controlled for in all three cohorts. These studies demonstrated that GPx activity, protein and mRNA levels were significantly elevated in the ACS patients compared to the stable coronary disease patients and healthy subjects. Oxidised low-density lipoprotein (oxLDL), a widely used marker of oxidative stress, was also significantly elevated in the ACS patients compared to the other two cohorts.  In a study examining the temporal changes in GPx activity in the acute phase of an ACS, GPx activity was found to be highly dynamic, with no consistent single time point that identified when peak activity occurred. In the majority of patients, levels of oxLDL were found to peak prior to, or at the same time, as peak GPx activity, suggesting that GPx activity was modulated by changes in oxidative stress.  In conclusion, the elevated levels of GPx activity observed in ACS patients were found to be highly dynamic throughout an ACS event. However those with lower levels of GPx activity have an increased risk of adverse clinical outcomes that may be due to an inadequate defence against levels of ROS. Whether these patients can be accurately identified and targeted with an appropriate therapeutic intervention warrants further investigation.</p>

scholarly journals Glutathione peroxidase in acute coronary syndromes

2021 ◽  
Author(s):  
◽  
Ana Simone Holley
Keyword(s):  
Oxidative Stress ◽  
Glutathione Peroxidase ◽  
Coronary Disease ◽  
Healthy Subjects ◽  
Acute Coronary Syndromes ◽  
Mrna Levels ◽  
Sod Activity ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
Gpx Activity

<p>Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are among the primary antioxidant enzymes that scavenge reactive oxygen species in the blood (ROS), thereby protecting against high levels of oxidative stress. The consequences of oxidative stress include cellular injury and tissue damage. High levels of oxidative stress have been implicated in the pathogenesis of acute coronary syndromes (ACS), however large clinical trials involving dietary antioxidant supplements have not shown a reduction in the rate of major adverse cardiovascular events (MACE).  In a cohort of 262 ACS patients we examined the relationship between GPx activity, SOD activity and MACE. Patients with MACE were found to have significantly lower levels of GPx activity than those without MACE, whereas SOD activity did not differ between the groups. Furthermore, dividing the patients into quartiles corresponding to levels of GPx activity demonstrated significantly higher rates of MACE in the lower quartile of GPx activity compared to the highest quartile.  Previous studies have demonstrated that deficiencies in GPx activity are associated with vascular dysfunction and platelet-dependent thrombosis, leading to the hypothesis that low levels of GPx activity would be associated with increased levels of platelet reactivity. In 51 ACS patients we did not observe a significant relationship between these two parameters, however we did demonstrate that increasing levels of GPx activity was associated with lower levels of ROS. ROS measures were based on the response of the platelets to addition of exogenous nitric oxide. Such an inverse relationship between GPx activity and levels of ROS is consistent with the view that GPx activity may play an important role in an ACS by reducing ROS-mediated damage, thereby protecting against MACE.  We examined levels of GPx activity, protein concentration and mRNA expression across populations of ACS patients, stable coronary disease patients and healthy subjects. Cardiovascular risk factors thought to influence levels of GPx activity were controlled for in all three cohorts. These studies demonstrated that GPx activity, protein and mRNA levels were significantly elevated in the ACS patients compared to the stable coronary disease patients and healthy subjects. Oxidised low-density lipoprotein (oxLDL), a widely used marker of oxidative stress, was also significantly elevated in the ACS patients compared to the other two cohorts.  In a study examining the temporal changes in GPx activity in the acute phase of an ACS, GPx activity was found to be highly dynamic, with no consistent single time point that identified when peak activity occurred. In the majority of patients, levels of oxLDL were found to peak prior to, or at the same time, as peak GPx activity, suggesting that GPx activity was modulated by changes in oxidative stress.  In conclusion, the elevated levels of GPx activity observed in ACS patients were found to be highly dynamic throughout an ACS event. However those with lower levels of GPx activity have an increased risk of adverse clinical outcomes that may be due to an inadequate defence against levels of ROS. Whether these patients can be accurately identified and targeted with an appropriate therapeutic intervention warrants further investigation.</p>

Plasma haemoxygenase-1 in coronary artery disease

2010 ◽  
Vol 104 (11) ◽  
pp. 1029-1037 ◽  
Author(s):  
Naglaa Idriss ◽  
Gregory Lip ◽  
Balu Balakrishnan ◽  
Rumi Jaumdally ◽  
Christopher Boos ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Umbilical Vein ◽  
Stable Coronary Artery Disease ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Healthy Controls ◽  
Coronary Syndromes ◽  
Artery Disease ◽  
Stable Cad ◽  
Umbilical Vein Endothelial Cells

SummaryIt was the aim of this study to determine plasma haemoxygenase-1 (HO-1) across the spectrum of health, angina but normal coronary arteries (NCA), stable coronary artery disease (CAD), and acute coronary syndromes (ACS), and relationships with angiogenin, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1, and vascular endothelial growth factor. Plasma markers were measured (ELISA) in peripheral venous citrated plasma from 50 healthy subjects, 30 with NCA, 70 with stable CAD and 24 with an ACS, and from patient’s aortic root, coronary ostium, coronary sinus and femoral artery. Human umbilical vein endothelial cells (HUVECs) were cultured with or without tumour necrosis factor (TNF), and platelets were probed. HO-1 was raised in stable CAD (p<0.05) and increased further in ACS (p<0.01) compared to healthy controls and NCA. HO-1 correlated only with MMP-9, and then only in the healthy controls. There were no major differences from cardiac or peripheral sites. HO-1 was present in HUVECs and 24-hour HUVEC supernatants but release was abolished by TNF. Platelets had no HO-1. In conclusion, HO-1 is raised in stable CAD and ACS and may arise from the endothelium but not the platelet. This may have implications for our understanding of the pathophysiology of CAD and its acute presentation as ACS.

scholarly journals Post-transcriptional regulation of glutathione peroxidase gene expression by selenium in the HL-60 human myeloid cell line

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2535-2541 ◽  
Author(s):  
S Chada ◽  
C Whitney ◽  
PE Newburger
Keyword(s):  
Glutathione Peroxidase ◽  
Enzymatic Activity ◽  
Cell Line ◽  
Myeloid Cell ◽  
Mrna Levels ◽  
Protein Levels ◽  
Myeloid Cell Line ◽  
Cloned Cdna ◽  
Post Transcriptional Regulation ◽  
Gpx Activity

We have used a cloned cDNA for the major human selenoprotein, glutathione peroxidase (GPx), to assess the mode of regulation of human GPx gene (GPX-1) expression by selenium. When the HL-60 human myeloid cell line is grown in a selenium-deficient medium, GPx enzymatic activity decreases 30-fold compared with selenium-replete cells. Upon return to a medium containing selenium in the form of selenite, GPx activity in the cells starts to increase within 48 hours and reaches maximal (selenium-replete) levels at 7 days. Steady-state immunoreactive protein levels correlate with enzymatic activity. Cycloheximide inhibits the rise in GPx activity that accompanies selenium replenishment, indicating that protein synthesis is required for the increase. However, GPx mRNA levels and the rate of transcription of the human GPx gene change very little and thus appear to be independent of the selenium supply. Thus the human GPx gene appears to be regulated post-transcriptionally, probably cotranslationally, in response to selenium availability.

Platelet Interactions with Von Willebrand Factor: Comparing Platelet Function in Acute and Stable Coronary Syndromes

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3829-3829
Author(s):  
Eimear Dunne ◽  
Adam Ralph ◽  
David Foley ◽  
Antonio J Ricco ◽  
Dermot Kenny
Keyword(s):  
Platelet Function ◽  
Research Funding ◽  
Surface Coverage ◽  
Stable Coronary Artery Disease ◽  
Healthy Controls ◽  
Coronary Syndromes ◽  
Artery Disease ◽  
Stable Cad ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract In unstable coronary syndromes, von Willebrand Factor (VWF) adheres to exposed subendothelial matrix. Initial platelet interaction with immobilised VWF is rapidly reversible, shear dependent, and includes characteristic start-stop translocation of platelets. Platelets tether to bound VWF via the glycoprotein (GP)Ib receptor and initiate a complex signalling cascade, ultimately activating the integrin αIIbβ3 receptor that crosslinks fibrinogen and causes platelet arrest. We have developed a microfluidic assay utilizing video microscopy to accurately measure dynamic platelet behaviour in microliters of blood perfused across VWF at arterial shear rates (1500 s-1). Tracking multiple individual platelets from frame to frame with unique motion-analysis software, the assay measures the total number of platelets 1) interacting with VWF, 2) translocating across VWF (GPIb dependent), and 3) stably adhered to the surface (αIIbβ3 dependent), as well as 4) the development rate of thrombi, and 5) the percent surface coverage at 17 sec (the end of the assay). Variations in platelet function associated with acute coronary syndromes (ACS) and stable coronary artery disease (CAD) are poorly understood. We hypothesise that platelet function differs between normal donors, patients with stable CAD taking aspirin (ASA), and patients with ACS on dual anti-platelet therapy (DAPT). We characterised dynamic platelet function in 66 healthy donors, 67 patients with stable CAD on long-term ASA alone and 85 patients recruited within 3 days of a cardiac event on DAPT (ACS group). All patients had an appropriate response to either ASA alone or DAPT as defined by consensus guidelines using light transmission aggregometry (LTA) in response to 500 mg/mL arachidonic acid and 20 mM ADP. Compared to healthy controls and despite an adequate LTA response to DAPT, patients with ACS had significantly more platelets interacting with VWF (534±281 vs 424±198 (mean±SD), p ² 0.01), stably adhered platelets (237±118 vs 189±69, p ² 0.01), translocating platelets (365±186 vs 303±141, p ² 0.04) and final surface coverage (12.8±3.7% vs 11.2±2.7%, p ² 0.002). The differences between CAD patients on ASA alone and those with ACS were even more striking: long-term-ASA CAD patients had fewer stably adhered (181±83 vs 237±118, p ² 0.002) and translocating platelets (271±141 vs 365±186, p ² 0.0006). Both the rate of thrombus growth (9.8±2.7 vs 8.6±2.7, p ² 0.005) and the percent surface coverage (12.8±3.7% vs 10.8±3.4%, p ² 0.0007) were significantly greater in ACS patients. Conclusion: Despite nominal LTA-measured response to DAPT, the profile of dynamic platelet behaviour measured by novel platelet function parameters is remarkably different in patients with ACS from those with stable CAD (Figure 1). Platelets from patients with ACS interact more with VWF compared to healthy controls and patients with stable coronary artery disease. Our dynamic platelet function assay describes for the first time novel platelet interactions with VWF suggesting a new way to guide antiplatelet therapy. Figure 1 The profile of platelet interactions with VWF is markedly different in patients with ACS. Dynamic platelet interaction with VWF in patients with ACS and stable CAD was normalised against healthy controls (bars represent normalised 95% confidence intervals). Platelets from patients with ACS have a higher rate of interaction with the surface compared to healthy controls and stable patients on aspirin alone. Figure 1. The profile of platelet interactions with VWF is markedly different in patients with ACS. Dynamic platelet interaction with VWF in patients with ACS and stable CAD was normalised against healthy controls (bars represent normalised 95% confidence intervals). Platelets from patients with ACS have a higher rate of interaction with the surface compared to healthy controls and stable patients on aspirin alone. Disclosures Dunne: Science Foundation Ireland: Research Funding. Ralph:Science Foundation Ireland: Research Funding. Ricco:Science Foundation Ireland: Research Funding. Kenny:Science Foundation Ireland: Research Funding; Enterprise Ireland: Research Funding.

scholarly journals Post-transcriptional regulation of glutathione peroxidase gene expression by selenium in the HL-60 human myeloid cell line

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2535-2541 ◽  
Author(s):  
S Chada ◽  
C Whitney ◽  
PE Newburger
Keyword(s):  
Glutathione Peroxidase ◽  
Enzymatic Activity ◽  
Cell Line ◽  
Myeloid Cell ◽  
Mrna Levels ◽  
Protein Levels ◽  
Myeloid Cell Line ◽  
Cloned Cdna ◽  
Post Transcriptional Regulation ◽  
Gpx Activity

Abstract We have used a cloned cDNA for the major human selenoprotein, glutathione peroxidase (GPx), to assess the mode of regulation of human GPx gene (GPX-1) expression by selenium. When the HL-60 human myeloid cell line is grown in a selenium-deficient medium, GPx enzymatic activity decreases 30-fold compared with selenium-replete cells. Upon return to a medium containing selenium in the form of selenite, GPx activity in the cells starts to increase within 48 hours and reaches maximal (selenium-replete) levels at 7 days. Steady-state immunoreactive protein levels correlate with enzymatic activity. Cycloheximide inhibits the rise in GPx activity that accompanies selenium replenishment, indicating that protein synthesis is required for the increase. However, GPx mRNA levels and the rate of transcription of the human GPx gene change very little and thus appear to be independent of the selenium supply. Thus the human GPx gene appears to be regulated post-transcriptionally, probably cotranslationally, in response to selenium availability.

scholarly journals Relative hypoxia and oxidative stress in spleen lymphocytes of immunized Balb/c mice as indicated by HIF-1α, HIF-2α, Nrf2 expression, and glutathione peroxidase activity

2018 ◽  
Vol 27 (4) ◽  
pp. 223-8 ◽  
Author(s):  
Citra Praditi ◽  
Ani R. Prijanti ◽  
Sri W.A. Jusman ◽  
Mohamad Sadikin
Keyword(s):  
Oxidative Stress ◽  
Glutathione Peroxidase ◽  
Buffy Coat ◽  
Mrna Levels ◽  
Post Immunization ◽  
Protein Levels ◽  
Spleen Lymphocytes ◽  
And Oxidative Stress ◽  
Gpx Activity ◽  
Nrf2 Protein

Background: Lymphocytes activated by immunization must increase their metabolism to meet the energy requirements for mitosis, differentiation, and protein synthesis, which may subject the cell to conditions of relative hypoxia and oxidative stress. This study was conducted to investigate the increase in the levels of transcription factors involved in both conditions.Methods: Male Balb/c mice were divided into the following four groups, each consisting of six animals: the control and three experimental groups. The experimental groups were immunized by injection of 0.2 ml of 2% sheep red blood cells (SRBC) suspended in phosphate-buffered saline (PBS). Lymphocytes were harvested from the spleens of each group at time intervals of 24-, 48-, and 72-h post-immunization. The buffy coat from splenocytes was separated using Ficoll Histopaque as the medium. The lymphocytes were separated from adherent cells by incubating the purified splenocytes in microtubes for 2-h. Cells were lysed by three freeze–thaw cycles (−80°C and 37°C) and used to analyze the levels of HIF-1α and HIF-2α (mRNA and protein), Nrf2 (protein), and glutathione peroxidase (GPx) activity.Results: The treatment caused an increase in GPx activity and HIF-1α protein concentration 24-h post-immunization, whereas the HIF-1α mRNA levels remained static. Elevated Nrf2 protein levels were detected within 48-h after treatment. Meanwhile, the HIF-2α mRNA and protein levels increased within72-h after immunization.Conclusion: Immunization with SRBC suspension induced relative hypoxia, elevated reactive oxygen species (ROS), and oxidative stress in the lymphocytes as indicated by the increase in both HIF-1α and HIF-2α protein and mRNA levels, GPx activity, and Nrf2 protein levels.

A Common Thrombomodulin Amino Acid Dimorphism Is Associated with Myocardial Infarction

1997 ◽  
Vol 77 (02) ◽  
pp. 248-251 ◽  
Author(s):  
Lena Norlund ◽  
Johan Holm ◽  
Bengt Zöller ◽  
Ann-Kristin Öhlin
Keyword(s):  
Myocardial Infarction ◽  
Amino Acid ◽  
Plasma Concentration ◽  
Acute Coronary Syndromes ◽  
Protein C ◽  
Integral Membrane Protein ◽  
Control Group ◽  
Healthy Controls ◽  
Coronary Syndromes ◽  
Premature Myocardial Infarction

SummaryEndothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for development of premature myocardial infarction (MI). The C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy controls. The C allele was significantly more frequent among patients than controls (p = 0.035). The allele frequency for the C allele was 0.82 in the patients and 0.72 in the control group. The plasma concentration of TM was investigated among healthy controls but was not related to the C/T dimorphism. In conclusion, the association of the C allele with premature MI, suggests that the TM gene and the C/T dimorphism may be aetiological factors involved in the pathogenesis of MI. Possibly, the Ala455 to Val replacement may affect the function of the TM molecule and the activation of the protein C anticoagulant pathway.

scholarly journals Analysis of Bioavailability and Induction of Glutathione Peroxidase by Dietary Nanoelemental, Organic and Inorganic Selenium

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1073
Author(s):  
Mitchell T. Ringuet ◽  
Billie Hunne ◽  
Markus Lenz ◽  
David M. Bravo ◽  
John B. Furness
Keyword(s):  
Glutathione Peroxidase ◽  
Similar Efficacy ◽  
Enzymatic Assays ◽  
Germ Free ◽  
Organic Selenium ◽  
Protein Levels ◽  
Antioxidant Protein ◽  
Inorganic Selenium ◽  
Fresh Frozen ◽  
Gpx Activity

Dietary organic selenium (Se) is commonly utilized to increase formation of selenoproteins, including the major antioxidant protein, glutathione peroxidase (GPx). Inorganic Se salts, such as sodium selenite, are also incorporated into selenoproteins, and there is evidence that nanoelemental Se added to the diet may also be effective. We conducted two trials, the first investigated inorganic Se (selenite), organic Se (L-selenomethionine) and nanoelemental Se, in conventional mice. Their bioavailability and effectiveness to increase GPx activity were examined. The second trial focused on determining the mechanism by which dietary Se is incorporated into tissue, utilising both conventional and germ-free (GF) mice. Mice were fed a diet with minimal Se, 0.018 parts per million (ppm), and diets with Se supplementation, to achieve 0.07, 0.15, 0.3 and 1.7 ppm Se, for 5 weeks (first trial). Mass spectrometry, Western blotting and enzymatic assays were used to investigate bioavailability, protein levels and GPx activity in fresh frozen tissue (liver, ileum, plasma, muscle and feces) from the Se fed animals. Inorganic, organic and nanoelemental Se were all effectively incorporated into tissues. The high Se diet (1.7 ppm) resulted in the highest Se levels in all tissues and plasma, independent of the Se source. Interestingly, despite being ~11 to ~25 times less concentrated than the high Se, the lower Se diets (0.07; 0.15) resulted in comparably high Se levels in liver, ileum and plasma for all Se sources. GPx protein levels and enzyme activity were significantly increased by each diet, relative to control. We hypothesised that bacteria may be a vector for the conversion of nanoelemental Se, perhaps in exchange for S in sulphate metabolising bacteria. We therefore investigated Se incorporation from low sulphate diets and in GF mice. All forms of selenium were bioavailable and similarly significantly increased the antioxidant capability of GPx in the intestine and liver of GF mice and mice with sulphate free diets. Se from nanoelemental Se resulted in similar tissue levels to inorganic and organic sources in germ free mice. Thus, endogenous mechanisms, not dependent on bacteria, reduce nanoelemental Se to the metabolite selenide that is then converted to selenophosphate, synthesised to selenocysteine, and incorporated into selenoproteins. In particular, the similar efficacy of nanoelemental Se in comparison to organic Se in both trials is important in the view of the currently limited cheap sources of Se.

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