scholarly journals Tongxinluo Improves Cardiac Function and Ameliorates Ventricular Remodeling in Mice Model of Myocardial Infarction through Enhancing Angiogenesis

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Wen-Wu Bai ◽  
Yi-Fan Xing ◽  
Bo Wang ◽  
Xiao-Ting Lu ◽  
Ying-Bin Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Binding Activity ◽  
Control Group ◽  
High Dose ◽  
Mice Model ◽  
Male Adult

Background. Myocardial infarction (MI) is a major cause of morbidity and mortality in the world. Tongxinluo (TXL) is a traditional Chinese compound prescription which has cardioprotective functions. The present study was aimed to determine the effect of TXL on postischemic cardiac dysfunction and cardiac remodeling and to elucidate the underlying mechanisms.Methods and Results. MI was performed by ligation of left anterior descending coronary artery (LAD) in male adult mice. Mice were randomly divided into four groups: (1) sham group (Sham); (2) MI-control group (Control); (3) MI-low dose TXL group (TXL-L); and (4) MI-high dose TXL (TXL-H) group. Compared with the control group, TXL treatment restored cardiac function, increased revascularization, attenuated cardiomyocyte apoptosis, and reduced interstitial fibrosis. TXL treatment increased the phosphorylation of Akt, extracellular signal regulated kinase (ERK), and endothelial nitric oxide synthase (eNOS); the expression of phosphatidylinositol3-kinase (PI3K), hypoxia-inducible factors 1α(HIF-1α), and vascular endothelial growth factor (VEGF); and the DNA binding activity of HIF-1αafter MI.Conclusion. TXL may improve cardiac function and ameliorate cardiac remodeling by increasing neovascularization through enhancing the phosphorylation of Akt and ERK, the expression and activity of HIF-1α, and the protein level of VEGF and p-eNOS.

scholarly journals Troponin T and Histological Characteristics of Rat Myocardial Infarction Induced by Isoproterenol

2007 ◽  
Vol 7 (3) ◽  
pp. 212-217 ◽  
Author(s):  
Sabaheta Hasić ◽  
Radivoj Jadrić ◽  
Emina Kiseljaković ◽  
Zakira Mornjaković ◽  
Mira Winterhalter-Jadrić
Keyword(s):  
Myocardial Infarction ◽  
Troponin T ◽  
Myocardial Necrosis ◽  
Control Group ◽  
High Dose ◽  
Male Adult ◽  
Histological Changes ◽  
Significant Difference ◽  
Intraperitoneal Dose ◽  
Histological Characteristics

In our investigation, we used short-time model of myocardial infarction of rats induced by high dose of isoproterenol (ISP). We investigated cardiac troponin T blood level (cTnT) and histological characteristics of rat myocardium. ISP, single, intraperitoneal dose 250 mg/kg was given to male, adult, Wistar rats (n=12). Rats were distributed depending on their body weight in subgroups: ISP I (BW 260-280g) and ISP II (BW 250-400g). Control group (n=9) was treated with intraperitoneal dose of 0,95% NaCl. Cardiac TnT was measured by electrochemiluminiscence (ECLA) sandwich immunoassay in rat serum 4 hours after ISP application. Rats’ hearts were dissected and examined by qualitative histological method (HE). Statistical significance was set at 0,05. There was significant difference in cTnT of ISP II (p=0,0001) vs. control and ISP I (p<0,05) vs. control. Significant difference was beetween ISP I and ISP II subgroups (p<0.001). The accent of histological changes of myocardium was on nuclei of cell. Cells showed acydophilic changes and nuclei disappearance as signs of coagulative necrosis development. Extensivity of histological changes were different beetween ISP I and ISP II subgroup. Used dose of ISP induced development of myocardial necrosis in rats. Suben-docardial portion of myocardium was more vulnerability than subepicardial portion. Rats of ISP II had more extensive histological changes than these in ISP I. Administered doses of ISP enabled cTnT utilization as a marker of myocardial necrosis.

Abstract 81: B Lymphocytes Trigger MCP3-Dependent Mobilization of Monocytes and Promote Adverse Ventricular Remodeling After Myocardial Infarction

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Yasmine Zouggari ◽  
Hafid Ait-Oufella ◽  
Philippe Bonnin ◽  
José Vilar ◽  
Coralie Guerin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Bone Marrow ◽  
Inflammatory Response ◽  
Cardiac Function ◽  
B Cell ◽  
B Lymphocytes ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Cell Depletion ◽  
B Cell Depletion

Leukocyte infiltration in ischemic areas is a hallmark of myocardial infarction, and persistent infiltration of innate immune cells, such as neutrophils and Ly6Chi monocytes, has been shown to promote adverse cardiac tissue remodeling. However, little is known regarding the role of mature B lymphocytes, which play a crucial role in the activation of the inflammatory response in several immune-mediated diseases. Here, we hypothesized that B lymphocytes might modulate the inflammatory response and affect the immune-dependent adverse cardiac remodeling. In a mouse model of myocardial infarction, cardiac B lymphocytes levels peaked at day 5 after the onset of infarction. Of interest, treatment with a CD20-specific monoclonal antibody decreased circulating and infiltrating B cell numbers (p=0.0008 and p=0.0002 vs control), reduced infarct size and post-ischemic immunoinflammatory response, and improved cardiac function (p=0.02 vs control) assessed by echocardiography. Intriguingly, B cell depletion was associated with an impairment of Ly6Chi monocytes mobilization from bone marrow (p=0.02 vs control), leading to reduced levels of circulating and infiltrating cardiac monocytes. The acute infarction led to transient increase of both MCP-1 and MCP-3 levels. Interestingly, B cell depletion was associated with a significant and selective reduction of MCP-3 (p=0.03 vs control) but did not alter MCP-1 levels (p=0.11). Cultured activated B cells released MCP-3 and treatment with a neutralizing MCP-3 antibody abrogated B lymphocytes-induced migration of cultured monocytes. Finally, transfer of B cell-depleted splenocytes into Rag1 -/- mice improved cardiac function after myocardial infarction compared to the transfer of non-depleted splenocytes (p=0.005). This effect was abrogated after re-supplementation with B lymphocytes isolated from wild-type mice (p=0.0007) but not from MCP-3-deficient animals (p=0.7008). In conclusion, we show that following acute myocardial infarction, B lymphocytes, trigger an MCP-3-dependent mobilization of Ly6Chi monocytes from the bone marrow to the blood, leading to their recruitment into the injured myocardium and to exacerbation of tissue inflammation, thereby promoting adverse cardiac remodeling.

Blockade of NF-κB improves cardiac function and survival after myocardial infarction

2006 ◽  
Vol 291 (3) ◽  
pp. H1337-H1344 ◽  
Author(s):  
Shunichi Kawano ◽  
Toru Kubota ◽  
Yoshiya Monden ◽  
Takaki Tsutsumi ◽  
Takahiro Inoue ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Diastolic Pressure ◽  
Interstitial Fibrosis ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Targeted Disruption ◽  
Ventricular Rupture ◽  
Inflammatory Processes

NF-κB is a key transcription factor that regulates inflammatory processes. In the present study, we tested the hypothesis that blockade of NF-κB ameliorates cardiac remodeling and failure after myocardial infarction (MI). Knockout mice with targeted disruption of the p50 subunit of NF-κB (KO) were used to block the activation of NF-κB. MI was induced by ligation of the left coronary artery in male KO and age-matched wild-type (WT) mice. NF-κB was activated in noninfarct as well as infarct myocardium in WT + MI mice, while the activity was completely abolished in KO mice. Blockade of NF-κB significantly reduced early ventricular rupture after MI and improved survival by ameliorating congestive heart failure. Echocardiographic and pressure measurements revealed that left ventricular fractional shortening and maximum rate of rise of left ventricular pressure were significantly increased and end-diastolic pressure was significantly decreased in KO + MI mice compared with WT + MI mice. Histological analysis demonstrated significant suppression of myocyte hypertrophy as well as interstitial fibrosis in the noninfarct myocardium of KO + MI mice. Blockade of NF-κB did not ameliorate expression of proinflammatory cytokines in infarct or noninfarct myocardium. In contrast, phosphorylation of c-Jun NH2-terminal kinase was almost completely abolished in KO + MI mice. The present study demonstrates that targeted disruption of the p50 subunit of NF-κB reduces ventricular rupture as well as improves cardiac function and survival after MI. Blockade of NF-κB might be a new therapeutic strategy to attenuate cardiac remodeling and failure after MI.

P6292Role of CXCL12gamma isoform and its interactions with heparan-sulfates in post-ischemic cardiac remodeling

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V Duval ◽  
I Zlatanova ◽  
Y Sun ◽  
P Alayrac ◽  
I Gomez ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Cardiac Tissue ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Vascular Growth ◽  
Heparan Sulfates

Abstract Introduction Myocardial infarction (MI) is a severe ischemic disease precipitating long-term adverse remodeling and heart failure. The chemokine CXCL12/SDF-1 is essential for cardiovascular system development and plays a prominent role in physio-pathological processes such as inflammation, angiogenesis and tissue fibrosis. In addition to the binding to its cognate receptors CXCR4 and CXCR7, CXCL12 interacts with heparan-sulfates (HS) which coordinate its biological activity. We have previously highlighted the essential role of CXCL12/HS interactions in vascular growth and remodeling in the setting of critical limb ischemia. In addition, studies in experimental model of MI revealed a protective role for the CXCL12α isoform, through the regulation of cardiomyocyte survival and recruitment of inflammatory cells. However, in mice, three CXCL12 isoforms (α, β and γ) have been identified and, among them, the CXCL12γ isoform shows an unchallenged ability to cooperate with HS, suggesting a putative pivotal role in tissue repair. Objectives The aim of the study is to analyze the role of CXCL12γ isoform and the importance of CXCL12/HS interactions in post-ischemic cardiac remodeling in an acute model of MI. Methods MI was induced by permanent ligation of the left ascending coronary artery in mice carrying a Cxcl12 gene mutation that precludes interactions with HS (Cxcl12Gagtm) and in Cxcl12γ knock-in animals (Cxcl12γ-KI) harboring CXCL12γ deficiency. Alternatively, the impact of CXCL12γ overexpression and the importance of its interactions with HS was also evaluated in wild-type (WT) mice receiving transcutaneous echo-guided injections of adenovirus encoding WT Cxcl12γ or HS-binding-disabled Cxcl12γ in cardiac tissue. Cardiac function and remodeling have been assessed through echocardiography analysis, evaluation of infarct size, interstitial fibrosis, vascular growth (capillary and arteriole densities) and inflammatory cell infiltration into the cardiac tissue. Results After MI, Cxcl12Gagtm and Cxcl12γ-KI animals exhibit reduction in cardiac function and adverse left ventricular remodeling when compared to their respective WT littermates. Interestingly, overexpression of CXCL12γ in WT mice cardiac restored cardiac function by reducing the size of the infarcted area, interstitial fibrosis and promoting vascular growth. In sharp contrast, HS–binding disabled CXCL12gamma mutants failed to improve cardiac function and to abrogate adverse left ventricular remodeling. Conclusion We show that CXCL12γ isoform plays an important role in the regulation of post-ischemic cardiac function and remodeling and that its interactions with HS are essential for adequate cardiac repair in the setting of acute MI.

OPC-28326, a selective peripheral vasodilator with angiogenic activity, mitigates postinfarction cardiac remodeling

2015 ◽  
Vol 309 (1) ◽  
pp. H213-H221 ◽  
Author(s):  
Atsushi Ogino ◽  
Genzou Takemura ◽  
Ayako Hashimoto ◽  
Hiromitsu Kanamori ◽  
Hideshi Okada ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Control Group ◽  
Proliferating Cells ◽  
Angiogenic Activity ◽  
Adrenergic Antagonist ◽  
Peripheral Vasodilator

Although OPC-28326, 4-( N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, was developed as a selective peripheral vasodilator with α2-adrenergic antagonist properties, it also reportedly exhibits angiogenic activity in an ischemic leg model. The purpose of this study was to examine the effect of OPC-28326 on the architectural dynamics and function of the infarcted left ventricle during the chronic stage of myocardial infarction. Myocardial infarction was induced in male C3H/He mice, after which the mice were randomly assigned into two groups: a control group receiving a normal diet and an OPC group whose diet contained 0.05% OPC-28326. The survival rate among the mice ( n = 18 in each group) 4 wk postinfarction was significantly greater in the OPC than control group (83 vs. 44%; P < 0.05), and left ventricular remodeling and dysfunction were significantly mitigated. Histologically, infarct wall thickness was significantly greater in the OPC group, due in part to an abundance of nonmyocyte components, including blood vessels and myofibroblasts. Five days postinfarction, Ki-67-positive proliferating cells were more abundant in the granulation tissue in the OPC group, and there were fewer apoptotic cells. These effects were accompanied by activation of myocardial Akt and endothelial nitric oxide synthase. Hypoxia within the infarct issue, assessed using pimonidazole staining, was markedly attenuated in the OPC group. In summary, OPC-28326 increased the nonmyocyte population in infarct tissue by increasing proliferation and reducing apoptosis, thereby altering the tissue dynamics such that wall stress was reduced, which might have contributed to a mitigation of postinfarction cardiac remodeling and dysfunction.

scholarly journals Qiliqiangxin Capsule Improves Cardiac Function and Attenuates Cardiac Remodeling by Upregulating miR-133a after Myocardial Infarction in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Huiyang Chen ◽  
Lixia Lou ◽  
Dongmei Zhang ◽  
Yizhou Zhao ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Volume Fraction ◽  
Left Ventricular ◽  
Control Group ◽  
Intragastric Administration ◽  
Model Group ◽  
Apoptosis Index ◽  
Cardiac Hemodynamics

Qiliqiangxin capsule (QLC), a natural herb recipe with therapeutic effect from China, has been widely used in clinical practice for attenuating cardiac remodeling induced by myocardial infarction (MI). However, the pharmacological mechanism of QLC on cardiac remodeling after MI is not entirely clear. The present study aims to investigate the effectiveness and mechanisms of QLC on cardiac remodeling induced by MI in rats. The animal model was established by permanently ligating the left anterior descending coronary artery in rats. Subsequently, rats with successful ligation were randomly divided into model group, captopril group, and QLC group. And the control group was operated upon in parallel except ligation, namely, the sham group. All rats were treated through the intragastric administration once a day for 4 weeks. Cardiac hemodynamics was measured after treatment. Then, the left ventricular mass index (LVMI) was examined. The pathological changes were observed by HE staining. The collagen volume fraction (CVF) was detected by Masson trichrome staining. The apoptosis index was obtained by TUNEL fluorescent staining. The miR-133a and mRNA of TGF-β1, CTGF, Caspase9, and Caspase3 were examined by real-time PCR. The protein expressions of TGF-β1, CTGF, Caspase9, Caspase3, and cleaved-Caspase3 were tested by Western blot. Compared with the model group, QLC partially improved cardiac hemodynamics and decreased LVMI. miR-133a was significantly increased in QLC group. In addition, QLC declined CVF by downregulating TGF-β1 rather than CTGF. Meanwhile, QLC decreased the apoptosis index by attenuating Caspase9, Caspase3, and cleaved-Caspase3. This study suggested that QLC could improve cardiac function and partially attenuate cardiac remodeling by attenuating fibrosis and decreasing apoptosis, which might be partially related to miR-133a, TGF-β1, Caspase9, and Caspase3.

scholarly journals Hydrogen Sulfide Reduces Recruitment of CD11b+DG Gr-1+DG Cells in Mice with Myocardial Infarction

2017 ◽  
Vol 26 (5) ◽  
pp. 753-764 ◽  
Author(s):  
Ting Wu ◽  
Hua Li ◽  
Bing Wu ◽  
Lei Zhang ◽  
San-Wu Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Hydrogen Sulfide ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Control Group ◽  
Coronary Artery Ligation ◽  
Sodium Hydrosulfide ◽  
Therapeutic Benefits

The present study aimed to elucidate the mechanisms by which hydrogen sulfide (H2S) attenuates left ventricular remodeling after myocardial infarction (MI). MI was created in mice by left coronary artery ligation. One group of mice received injections of the H2S donor sodium hydrosulfide (NaHS) immediately before and 1 h after ligation, while the control group received saline alone. During both the subacute and chronic stages (1 and 4 weeks postinfarction, respectively), NaHS-treated mice demonstrated attenuation of cardiac dilation in the infarcted myocardium. Furthermore, fewer CD11b+Gr-1+ myeloid cells were detected in the infarct myocardium and peripheral blood from NaHS-treated mice, while more CD11b+ Gr-1+ cells remained in the spleen and bone marrow in these animals. NaHS-treated mice also exhibited reduction in cardiomyocyte apoptosis, interstitial fibrosis, cardiac hypertrophy, and pulmonary edema, as well as overall better survival rates, when compared to controls. Thus, exogenous H2S has favorable effects on cardiac remodeling after MI. These observations further support the emerging concept that H2S treatment might have therapeutic benefits in the setting of ischemia-induced heart failure.

scholarly journals Targeted Cardiac Overexpression of A20 Improves Left Ventricular Performance and Reduces Compensatory Hypertrophy After Myocardial Infarction

Circulation ◽  
2007 ◽  
Vol 115 (14) ◽  
pp. 1885-1894 ◽  
Author(s):  
Hong-Liang Li ◽  
Ming-Lei Zhuo ◽  
Dong Wang ◽  
Ai-Bing Wang ◽  
Hua Cai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Interstitial Fibrosis ◽  
Nuclear Factor Κb ◽  
Left Ventricular ◽  
Nuclear Factor ◽  
Ventricular Performance

Background— A20 was originally characterized as a tumor necrosis factor–inducible gene in human umbilical vein endothelial cells. As an inhibitor of nuclear factor-κB signaling, A20 protects against apoptosis, inflammation, and cardiac hypertrophy. In the present study, we tested the hypothesis that cardiac-specific overexpression of A20 could protect the heart from myocardial infarction. Methods and Results— We investigated the role of constitutive human A20 expression in acute myocardial infarction using a transgenic model. Transgenic mice containing the human A20 gene under the control of the α-myosin heavy chain promoter were constructed. Myocardial infarction was produced by coronary ligation in A20 transgenic mice and control animals. The extent of infarction was then quantified by 2-dimensional and M-mode echocardiography and by molecular and pathological analyses of heart samples in infarct and remote heart regions 7 days after myocardial infarction. Constitutive overexpression of A20 in the murine heart resulted in attenuated infarct size and improved cardiac function 7 days after myocardial infarction. Significantly, we found a decrease in nuclear factor-κB signaling and apoptosis, as well as proinflammatory response, cardiac remodeling, and interstitial fibrosis, in noninfarct regions in the hearts of constitutive A20-expressing animals compared with control animals. Conclusions— Cardiac-specific overexpression of A20 improves cardiac function and inhibits cardiac remodeling, apoptosis, inflammation, and fibrosis after acute myocardial infarction.

scholarly journals Hepatocyte growth factor intervention to reduce myocardial injury and improve cardiac function on diabetic myocardial infarction rats

2020 ◽  
Vol 64 (s2) ◽  
Author(s):  
Zaiyong Zhang ◽  
Cheng Long ◽  
Yufeng Guan ◽  
Mingcai Song
Keyword(s):  
Myocardial Infarction ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Myocardial Cell ◽  
Diabetic Rats ◽  
Control Group ◽  
Myocardial Apoptosis ◽  
Hepatocyte Growth

Acute myocardial infarction (AMI) is recognized to be a severe threat to people’s health conditions and life quality. The accumulation of hepatocyte growth factor (HGF) in ischemic myocardium has been observed in both processes of experimental ischemia and reperfusion (I/R) and permanent coronary artery occlusion. The aim of the study was to investigate the effect of HGF on myocardial cell apoptosis, ventricular remodeling and cardiac function after myocardial infarction (MI) in diabetic rats, and to explore whether the effect is mediated by HGF/c-Met signaling pathway. MI significantly increases LVWI and RVWI and myocardial apoptotic index, and up-regulates the expression of HGF and c-Met at mRNA and protein levels in MI control group. The LVWI and RVWI, and myocardial apoptosis were reduced by treatment with HGF, which also increased the myocardial cell viability and the expression of HGF and c-Met. In summary, HGF significantly attenuates myocardial apoptosis and improves cardiac function after AMI in diabetic rats by further enhancing the activation of HGF/c-Met pathway.

PHENOTYPIC HETEROGENEITY OF CARDIAC MACROPHAGES DURING WOUND HEALING FOLLOWING MYOCARDIAL INFARCTION: PERSPECTIVES IN CLINICAL RESEARCH

2018 ◽  
Vol 33 (2) ◽  
pp. 70-76 ◽  
Author(s):  
A. E. Gombozhapova ◽  
Yu. V. Rogovskaya ◽  
M. S. Rebenkova ◽  
J. G. Kzhyshkowska ◽  
V. V. Ryabov
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Cardiac Remodeling ◽  
Phenotypic Heterogeneity ◽  
Macrophage Infiltration ◽  
Myocardial Regeneration ◽  
Control Group ◽  
M2 Macrophage ◽  
Inflammatory Phase ◽  
Regenerative Phase

Purpose. Myocardial regeneration is one of the most ambitious goals in prevention of adverse cardiac remodeling. Macrophages play a key role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). We have accumulated data on macrophage properties ex vivo and in cell culture. However, there is no clear information about phenotypic heterogeneity of cardiac macrophages in patients with MI. The purpose of the project was to assess cardiac macrophage infiltration during wound healing following myocardial infarction in clinical settings taking into consideration experimental knowledge.Material and Methods. The study included 41 patients with fatal MI type 1. In addition to routine analysis, macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163, CD206, and stabilin-1 were considered as M2 macrophage biomarkers. Nine patients who died from noncardiovascular causes comprised the control group.Results. The intensity of cardiac macrophage infiltration was higher during the regenerative phase than during the inflammatory phase. Results of immunohistochemical analysis demonstrated the presence of phenotypic heterogeneity of cardiac macrophages in patients with MI. We noticed that numbers of CD68+, CD163+, CD206+, and stabilin-1+ macrophages depended on MI phase.Conclusion. Our study supports prospects for implementation of macrophage phenotyping in clinic practice. Improved understanding of phenotypic heterogeneity might become the basis of a method to predict adverse cardiac remodeling and the first step in developing myocardial regeneration target therapy.

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