γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury

The mechanisms underlying sepsis-induced cardiomyopathy (SIC) remain poorly understood, and there are no specific therapeutics for SIC. We investigated the effects of maresin conjugates in tissue regeneration 1 (MCTR1) on SIC and explored its potential mechanisms. The experiments were conducted using an endotoxemia model induced by lipopolysaccharide (LPS). Mice were given MCTR1 intravenously 6 h after LPS stimulation. Echocardiography was performed to assess cardiac function 12 h after LPS administration. Treatment with MCTR1 significantly enhanced cardiac function and reduced LPS-induced increase of mRNA expression levels of inflammation cytokines. Transcriptomic analysis indicated that MCTR1 inhibited neutrophil chemotaxis via the IL-17 signaling pathway. We confirmed that MCTR1 reduced the expressions of neutrophil chemoattractants and neutrophil infiltration in the LPS-stimulated hearts. MCTR1 also resulted in a considerable reduction in IL-17A production mainly derived from γδ T cells. Moreover, our results provided the first evidence that neutralizing IL-17A or depletion of γδ T cells markedly decreased neutrophil recruitment and enhanced cardiac function in LPS-induced cardiac injury. These results suggest that MCTR1 alleviates neutrophil infiltration thereby improves cardiac function in LPS-induced cardiac injury via the IL-17 signaling pathway. Thus, MCTR1 represented a novel therapeutic strategy for patients with SIC.

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Myocardial NF-κB activation is essential for zebrafish heart regeneration

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1511209112 ◽

2015 ◽

Vol 112 (43) ◽

pp. 13255-13260 ◽

Cited By ~ 54

Author(s):

Ravi Karra ◽

Anne K. Knecht ◽

Kazu Kikuchi ◽

Kenneth D. Poss

Keyword(s):

Tissue Regeneration ◽

Therapeutic Strategy ◽

Cardiac Injury ◽

Regulatory Sequences ◽

Heart Regeneration ◽

Cardiomyocyte Proliferation ◽

Developmental Program ◽

Lower Vertebrates ◽

Outstanding Question ◽

Zebrafish Heart

Heart regeneration offers a novel therapeutic strategy for heart failure. Unlike mammals, lower vertebrates such as zebrafish mount a strong regenerative response following cardiac injury. Heart regeneration in zebrafish occurs by cardiomyocyte proliferation and reactivation of a cardiac developmental program, as evidenced by induction of gata4 regulatory sequences in regenerating cardiomyocytes. Although many of the cellular determinants of heart regeneration have been elucidated, how injury triggers a regenerative program through dedifferentiation and epicardial activation is a critical outstanding question. Here, we show that NF-κB signaling is induced in cardiomyocytes following injury. Myocardial inhibition of NF-κB activity blocks heart regeneration with pleiotropic effects, decreasing both cardiomyocyte proliferation and epicardial responses. Activation of gata4 regulatory sequences is also prevented by NF-κB signaling antagonism, suggesting an underlying defect in cardiomyocyte dedifferentiation. Our results implicate NF-κB signaling as a key node between cardiac injury and tissue regeneration.

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Blockade of RBP-J-Mediated Notch Signaling Pathway Exacerbates Cardiac Remodeling after Infarction by Increasing Apoptosis in Mice

BioMed Research International ◽

10.1155/2018/5207031 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Yanru He ◽

Si Pang ◽

Jia Huang ◽

Kongbo Zhu ◽

Jiayi Tong ◽

...

Keyword(s):

Cardiac Function ◽

Notch Signaling ◽

Signaling Pathway ◽

Cardiac Remodeling ◽

Ventricular Remodeling ◽

Cardiac Injury ◽

Notch Signaling Pathway ◽

Protective Role ◽

Cardiomyocyte Apoptosis

Background. Ischemic heart disease (IHD) is the major cause of death in patients with cardiovascular disease. Cardiac remodeling is a common pathological change following myocardial infarction (MI), and cardiomyocyte apoptosis plays a key role in this change. Transcription factor recombination signal-binding protein-J (RBP-J)-mediated Notch signaling pathway has been implicated in several inherited cardiovascular diseases, including aortic valve diseases, but whether the RBP-J-mediated Notch signaling pathway plays a role in cardiomyocyte apoptosis after MI is unclear. Method. We crossed RBP-Jfl/fl mice and Myh6-Cre/Esr1 transgenic mice to delete RBP-J in vivo and to partly inhibit the canonical Notch signaling pathway. MI was induced in mice by permanent ligation of the left anterior descending coronary artery followed by the knockout of RBP-J. Cardiac function and morphology were assessed by echocardiography and histological analysis 4 weeks after infarction. In addition, the expression and regulation of apoptosis-related molecules were examined by real time PCR and western blot. Results. RBP-J knockout decreased the survival rate and deteriorated post-MI remodeling and function in mice, and this effect was associated with increased cardiomyocyte apoptosis. The potential mechanisms might be related to the downregulated expression of bcl-2, upregulated expression of bax, and cleaved-caspase 3 to exacerbate cardiomyocyte apoptosis. Conclusion. These findings show that the RBP-J-mediated Notch signaling pathway in cardiomyocytes limits ventricular remodeling and improves cardiac function after MI. The RBP-J-mediated Notch signaling pathway has a protective role in cardiomyocyte apoptosis following cardiac injury.

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Asiatic Acid Protects against Doxorubicin-Induced Cardiotoxicity in Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5347204 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Xiaoping Hu ◽

Baijun Li ◽

Luocheng Li ◽

Bowen Li ◽

Jinlong Luo ◽

...

Keyword(s):

Cardiac Function ◽

Signaling Pathway ◽

Cardiac Injury ◽

Akt Signaling ◽

Cardiac Complications ◽

Asiatic Acid ◽

Protective Effects ◽

Akt Signaling Pathway ◽

Myocardial Oxidative Stress

The use of doxorubicin (DOX) can result in depression of cardiac function and refractory cardiomyopathy. Currently, there are no effective approaches to prevent DOX-related cardiac complications. Asiatic acid (AA) has been reported to provide cardioprotection against several cardiovascular diseases. However, whether AA could attenuate DOX-related cardiac injury remains unclear. DOX (15 mg/kg) was injected intraperitoneally into the mice to mimic acute cardiac injury, and the mice were given AA (10 mg/kg or 30 mg/kg) for 2 weeks for protection. The data in our study found that AA-treated mice exhibited attenuated cardiac injury and improved cardiac function in response to DOX injection. AA also suppressed myocardial oxidative damage and apoptosis without affecting cardiac inflammation in DOX-treated mice. AA also provided protection in DOX-challenged cardiomyocytes, improved cell viability, and suppressed intracellular reactive oxygen species (ROS) in vitro. Detection of signaling pathways showed that AA activated protein kinase B (AKT) signaling pathway in vivo and in vitro. Furthermore, we found that AA lost its protective effects in the heart with AKT inactivation. In conclusion, our results found that AA could attenuate DOX-induced myocardial oxidative stress and apoptosis via activation of the AKT signaling pathway.

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Targeting the Akt/PI3K Signaling Pathway as a Potential Therapeutic Strategy for the Treatment of Pancreatic Cancer

Current Medicinal Chemistry ◽

10.2174/0929867324666170206142658 ◽

2017 ◽

Vol 24 (13) ◽

Cited By ~ 50

Author(s):

Safieh Ebrahimi ◽

Mina Hosseini ◽

Soodabeh Shahidsales ◽

Mina Maftouh ◽

Gordon A. Ferns ◽

...

Keyword(s):

Pancreatic Cancer ◽

Signaling Pathway ◽

Therapeutic Strategy ◽

Pi3k Signaling ◽

Pi3k Signaling Pathway

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Bioinformatics Analysis Identifies CPZ as a Tumor Immunology Biomarker For Gastric Cancer

Current Bioinformatics ◽

10.2174/1574893615999200707145643 ◽

2020 ◽

Vol 15 ◽

Author(s):

Yuan Gu ◽

Ying Gao ◽

Xiaodan Tang ◽

Huizhong Xia ◽

Kunhe Shi

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Signaling Pathway ◽

Tumor Immunology ◽

Bioinformatics Analysis ◽

Human Cancer ◽

Disease Free Survival ◽

Kaplan Meier ◽

Potential Biomarker ◽

Pathway Regulation

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.

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The Nuclear Zinc Finger Protein Zfat Maintains FoxO1 Protein Levels in Peripheral T Cells by Regulating the Activities of Autophagy and the Akt Signaling Pathway

Journal of Biological Chemistry ◽

10.1074/jbc.m116.723734 ◽

2016 ◽

Vol 291 (29) ◽

pp. 15282-15291 ◽

Cited By ~ 8

Author(s):

Shuhei Ishikura ◽

Yuri Iwaihara ◽

Yoko Tanaka ◽

Hao Luo ◽

Kensuke Nishi ◽

...

Keyword(s):

T Cells ◽

Signaling Pathway ◽

Zinc Finger ◽

Zinc Finger Protein ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Protein Levels ◽

Finger Protein ◽

Peripheral T Cells

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Dermal γδ T Cells Do Not Freely Re-Circulate Out of Skin and Produce IL-17 to Promote Neutrophil Infiltration during Primary Contact Hypersensitivity

PLoS ONE ◽

10.1371/journal.pone.0169397 ◽

2017 ◽

Vol 12 (1) ◽

pp. e0169397 ◽

Cited By ~ 24

Author(s):

Xiaodong Jiang ◽

Chang Ook Park ◽

Jenna Geddes Sweeney ◽

Min Jae Yoo ◽

Olivier Gaide ◽

...

Keyword(s):

T Cells ◽

Γδ T Cells ◽

Neutrophil Infiltration ◽

Contact Hypersensitivity ◽

Primary Contact

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Importance of murine Vδ1+γδ T cells expressing interferon-γ and interleukin-17A in innate protection againstListeria monocytogenesinfection

Immunology ◽

10.1111/j.1365-2567.2008.02841.x ◽

2008 ◽

Vol 125 (2) ◽

pp. 170-177 ◽

Cited By ~ 39

Author(s):

Satoru Hamada ◽

Masayuki Umemura ◽

Takeru Shiono ◽

Hiromitsu Hara ◽

Kenji Kishihara ◽

...

Keyword(s):

T Cells ◽

Γδ T Cells ◽

Interferon Γ ◽

Interleukin 17A

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Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00844.2012 ◽

2013 ◽

Vol 305 (4) ◽

pp. H542-H550 ◽

Cited By ~ 22

Author(s):

Toshihiro Shinbo ◽

Kenichi Kokubo ◽

Yuri Sato ◽

Shintaro Hagiri ◽

Ryuji Hataishi ◽

...

Keyword(s):

Nitric Oxide ◽

Cardiac Function ◽

Infarct Size ◽

Ischemia Reperfusion Injury ◽

Myocardial Dysfunction ◽

Ischemia Reperfusion ◽

Neutrophil Infiltration ◽

Left Ventricular ◽

Hydrogen Gas ◽

Coronary Artery Ligation

Inhaled nitric oxide (NO) has been reported to decrease the infarct size in cardiac ischemia-reperfusion (I/R) injury. However, reactive nitrogen species (RNS) produced by NO cause myocardial dysfunction and injury. Because H2 is reported to eliminate peroxynitrite, it was expected to reduce the adverse effects of NO. In mice, left anterior descending coronary artery ligation for 60 min followed by reperfusion was performed with inhaled NO [80 parts per million (ppm)], H2 (2%), or NO + H2, starting 5 min before reperfusion for 35 min. After 24 h, left ventricular function, infarct size, and area at risk (AAR) were assessed. Oxidative stress associated with reactive oxygen species (ROS) was evaluated by staining for 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal, that associated with RNS by staining for nitrotyrosine, and neutrophil infiltration by staining for granulocyte receptor-1. The infarct size/AAR decreased with breathing NO or H2 alone. NO inhalation plus H2 reduced the infarct size/AAR, with significant interaction between the two, reducing ROS and neutrophil infiltration, and improved the cardiac function to normal levels. Although nitrotyrosine staining was prominent after NO inhalation alone, it was eliminated after breathing a mixture of H2 with NO. Preconditioning with NO significantly reduced the infarct size/AAR, but not preconditioning with H2. In conclusion, breathing NO + H2 during I/R reduced the infarct size and maintained cardiac function, and reduced the generation of myocardial nitrotyrosine associated with NO inhalation. Administration of NO + H2 gases for inhalation may be useful for planned coronary interventions or for the treatment of I/R injury.

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