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  • 1
    Online Resource
    Online Resource
    Restoration of Circulating MFGE8 (Milk Fat Globule-EGF Factor 8) Attenuates Cardiac Hypertrophy Through Inhibition of Akt Pathway
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Hypertension Vol. 70, No. 4 ( 2017-10), p. 770-779
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 70, No. 4 ( 2017-10), p. 770-779
    Abstract: Cardiac hypertrophy occurs in response to numerous stimuli like neurohumoral stress, pressure overload, infection, and injury, and leads to heart failure. Mfge8 (milk fat globule-EGF factor 8) is a secreted protein involved in various human diseases, but its regulation and function during cardiac hypertrophy remain unexplored. Here, we found that circulating MFGE8 levels declined significantly in failing hearts from patients with dilated cardiomyopathy. Correlation analyses revealed that circulating MFGE8 levels were negatively correlated with the severity of cardiac dysfunction and remodeling in affected patients. Deleting Mfge8 in mice maintained normal heart function at basal level but substantially exacerbated the hypertrophic enlargement of cardiomyocytes, reprogramming of pathological genes, contractile dysfunction, and myocardial fibrosis after aortic banding surgery. In contrast, cardiac-specific Mfge8 overexpression in transgenic mice significantly blunted aortic banding–induced cardiac hypertrophy. Whereas MAPK (mitogen-activated protein kinase) pathways were unaffected in either Mfge8 -knockout or Mfge8 -overexpressing mice, the activated Akt/PKB (protein kinase B)–Gsk-3β (glycogen synthase kinase-3β)/mTOR (mammalian target of rapamycin) pathway after aortic banding was significantly potentiated by Mfge8 deficiency but suppressed by Mfge8 overexpression. Inhibition of Akt with MK-2206 blocked the prohypertrophic effects of Mfge8 deficiency in angiotensin II–treated neonatal rat cardiomyocytes. Finally, administering a recombinant human MFGE8 in mice in vivo alleviated cardiac hypertrophy induced by aortic banding. Our findings indicate that Mfge8 is an endogenous negative regulator of pathological cardiac hypertrophy and may, thus, have potential both as a novel biomarker and as a therapeutic target for treatment of cardiac hypertrophy.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.117.09465
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2094210-2
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  • 2
    Online Resource
    Online Resource
    SHF confers radioresistance in colorectal cancer by the regulation of mitochondrial DNA copy number
    Springer Science and Business Media LLC ; 2022
    In:  Clinical and Experimental Medicine Vol. 23, No. 6 ( 2022-12-17), p. 2457-2471
    Details
    In: Clinical and Experimental Medicine, Springer Science and Business Media LLC, Vol. 23, No. 6 ( 2022-12-17), p. 2457-2471
    Type of Medium: Online Resource
    ISSN: 1591-9528
    URL: Article
    DOI: 10.1007/s10238-022-00969-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2054398-0
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  • 3
    Online Resource
    Online Resource
    Interferon Regulatory Factor 4 Inhibits Neointima Formation by Engaging Krüppel-Like Factor 4 Signaling
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation Vol. 136, No. 15 ( 2017-10-10), p. 1412-1433
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. 15 ( 2017-10-10), p. 1412-1433
    Abstract: The mechanisms underlying neointima formation remain unclear. Interferon regulatory factors (IRFs), which are key innate immune regulators, play important roles in cardiometabolic diseases. However, the function of IRF4 in arterial restenosis is unknown. Methods: IRF4 expression was first detected in human and mouse restenotic arteries. Then, the effects of IRF4 on neointima formation were evaluated with universal IRF4-deficient mouse and rat carotid artery injury models. We performed immunostaining to identify IRF4-expressing cells in the lesions. Smooth muscle cell (SMC)–specific IRF4-knockout (KO) and -transgenic (TG) mice were generated to evaluate the effects of SMC-IRF4 on neointima formation. We used microarray, bioinformatics analysis, and chromatin immunoprecipitation assay to identify the downstream signals of IRF4 and to verify the targets in vitro. We compared SMC-IRF4-KO/Krüppel-like factor 4 (KLF4)–TG mice with SMC-IRF4-KO mice and SMC-specific IRF4-TG/KLF4-KO mice with SMC-specific IRF4-TG mice to investigate whether the effect of IRF4 on neointima formation is KLF4-dependent. The effect of IRF4 on SMC phenotype switching was also evaluated. Results: IRF4 expression in both the human and mouse restenotic arteries is eventually downregulated. Universal IRF4 ablation potentiates neointima formation in both mice and rats. Immunostaining indicated that IRF4 was expressed primarily in SMCs in restenotic arteries. After injury, SMC-IRF4-KO mice developed a thicker neointima than control mice. This change was accompanied by increased SMC proliferation and migration. However, SMC-specific IRF4-TG mice exhibited the opposite phenotype, demonstrating that IRF4 exerts protective effects against neointima formation. The mechanistic study indicated that IRF4 promotes KLF4 expression by directly binding to its promoter. Genetic overexpression of KLF4 in SMCs largely reversed the neointima-promoting effect of IRF4 ablation, whereas ablation of KLF4 abolished the protective function of IRF4, indicating that the protective effects of IRF4 against neointima formation are KLF4-dependent. In addition, IRF4 promoted SMC dedifferentiation. Conclusions: IRF4 protects arteries against neointima formation by promoting the expression of KLF4 by directly binding to its promoter. Our findings suggest that this previously undiscovered IRF4-KLF4 axis plays a key role in vasculoproliferative pathology and may be a promising therapeutic target for the treatment of arterial restenosis.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.116.026046
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1466401-X
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  • 4
    Online Resource
    Online Resource
    The Ubiquitin E3 Ligase TRAF6 Exacerbates Ischemic Stroke by Ubiquitinating and Activating Rac1
    Society for Neuroscience ; 2017
    In:  The Journal of Neuroscience Vol. 37, No. 50 ( 2017-12-13), p. 12123-12140
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 37, No. 50 ( 2017-12-13), p. 12123-12140
    Abstract: Stroke is one of the leading causes of morbidity and mortality worldwide. Inflammation, oxidative stress, apoptosis, and excitotoxicity contribute to neuronal death during ischemic stroke; however, the mechanisms underlying these complicated pathophysiological processes remain to be fully elucidated. Here, we found that the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) was markedly increased after cerebral ischemia/reperfusion (I/R) in mice. TRAF6 ablation in male mice decreased the infarct volume and neurological deficit scores and decreased proinflammatory signaling, oxidative stress, and neuronal death after cerebral I/R, whereas transgenic overexpression of TRAF6 in male mice exhibited the opposite effects. Mechanistically, we demonstrated that TRAF6 induced Rac1 activation and consequently promoted I/R injury by directly binding and ubiquitinating Rac1. Either functionally mutating the TRAF6 ubiquitination site on Rac1 or inactivating Rac1 with a specific inhibitor reversed the deleterious effects of TRAF6 overexpression during I/R injury. In conclusion, our study demonstrated that TRAF6 is a key promoter of ischemic signaling cascades and neuronal death after cerebral I/R injury. Therefore, the TRAF6/Rac1 pathway might be a promising target to attenuate cerebral I/R injury. SIGNIFICANCE STATEMENT Stroke is one of the most severe and devastating neurological diseases globally. The complicated pathophysiological processes restrict the translation of potential therapeutic targets into medicine. Further elucidating the molecular mechanisms underlying cerebral ischemia/reperfusion injury may open a new window for pharmacological interventions to promote recovery from stroke. Our study revealed that ischemia-induced tumor necrosis factor receptor-associated factor 6 (TRAF6) upregulation binds and ubiquitinates Rac1 directly, which promotes neuron death through neuroinflammation and neuro-oxidative signals. Therefore, precisely targeting the TRAF6-Rac1 axis may provide a novel therapeutic strategy for stroke recovery.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.1751-17.2017
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2017
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Dickkopf‐3 Ablation Attenuates the Development of Atherosclerosis in ApoE‐Deficient Mice
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Journal of the American Heart Association Vol. 6, No. 2 ( 2017-02-02)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 2 ( 2017-02-02)
    Abstract: Dickkopf‐3 ( DKK 3) is a negative regulator of the Wnt/β‐catenin signaling pathway, which is involved in inflammation. However, little is known about the relationship between DKK 3 expression and the progression of atherosclerosis. The aim of the present study was to define the role of DKK 3 and its potential mechanism in the development of atherosclerosis. Methods and Results Immunofluorescence analysis showed that DKK 3 was strongly expressed in macrophages of atherosclerotic plaques from patients with coronary heart disease and in hyperlipidemic mice. The expression level was significantly increased in atherogenesis. DKK 3 −/− ApoE −/− mice exhibited a significant decrease in atherosclerotic lesions in the entire aorta, aortic sinus, and brachiocephalic arteries. Transplantation of bone marrow from DKK 3 −/− ApoE −/− mice into lethally irradiated ApoE −/− recipients resulted in a reduction of atherosclerotic lesions, compared with the lesions in recipients transplanted with ApoE −/− donor cells, suggesting that the effect of DKK 3 deficiency was largely mediated by bone marrow–derived cells. A reduction in the necrotic core size, accompanied by increased collagen content and smooth muscle cells and decreased accumulation of macrophages and lipids, contributed to the stability of plaques in DKK 3 −/− ApoE −/− mice. Furthermore, multiple proinflammatory cytokines exhibited marked decreases in DKK 3 −/− ApoE −/− mice. Finally, we observed that DKK 3 ablation increased β‐catenin expression in the nuclei of macrophages both in vivo and in vitro. Conclusions DKK 3 expression in macrophages is involved in the pathogenesis of atherosclerosis through modulation of inflammation and inactivation of the Wnt/β‐catenin pathway.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.116.004690
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2653953-6
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  • 6
    Online Resource
    Online Resource
    Late Cenozoic tectonic activity and its significance in the Northern Junggar Basin, Northwestern China
    Elsevier BV ; 2011
    In:  Tectonophysics Vol. 497, No. 1-4 ( 2011-1), p. 45-56
    Details
    In: Tectonophysics, Elsevier BV, Vol. 497, No. 1-4 ( 2011-1), p. 45-56
    Type of Medium: Online Resource
    ISSN: 0040-1951
    URL: Article
    DOI: 10.1016/j.tecto.2010.10.018
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 2012830-7
    detail.hit.zdb_id: 204243-5
    SSG: 16,13
    SSG: 13
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  • 7
    Online Resource
    Online Resource
    Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility
    Springer Science and Business Media LLC ; 2017
    In:  Journal of Translational Medicine Vol. 15, No. 1 ( 2017-12)
    Details
    In: Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2017-12)
    Type of Medium: Online Resource
    ISSN: 1479-5876
    URL: Article
    DOI: 10.1186/s12967-016-1105-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2118570-0
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  • 8
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    Online Resource
    Cerebral infarction and risk factors in acute type A aortic dissection with arch branch extension
    Wiley ; 2022
    In:  Echocardiography Vol. 39, No. 8 ( 2022-08), p. 1113-1121
    Details
    In: Echocardiography, Wiley, Vol. 39, No. 8 ( 2022-08), p. 1113-1121
    Abstract: Stanford type A aortic dissection (AAD) may affect the supra‐aortic arteries, which are associated with acute ischemic stroke (AIS) or transient ischemic attack (TIA). This study aimed to investigate cerebral perfusion, the infarction incidence and risk factors in AAD patients. Methods A total of 156 consecutive AAD patients were enrolled and divided into two groups according to whether the aortic arch branches were involved: the affected group ( n = 90) and the unaffected group ( n = 66). Clinical, echocardiographic/carotid Doppler data and cerebral infarction morbidity were compared between the groups. Independent predictors of 30‐day AAD mortality were identified through multivariable Cox regression, and perioperative risk factors were analyzed. Results In total, 57.7% of AAD patients had aortic arch branch involvement. Abnormal Doppler waveforms were more common in the affected group ( p 〈  0.05). Regarding intracranial perfusion, the blood flow volumes (BFVs) of the bilateral internal carotid arteries (ICAs) and right vertebral artery (RVA) in the affected group were significantly reduced ( p 〈  0.05). The incidence of cerebral infarction in the affected group was significantly higher than that in the unaffected group (35.6% vs. 19.7%, p = 0.031). Multivariable analysis revealed that age 〉 45 years old, right internal carotid artery (RICA) involvement and reduced left ventricular ejection fraction (LVEF) were significant predictors of perioperative death. Conclusions Aortic arch branch involvement is common in patients with AAD and is associated with reduced cerebral blood flow (especially on the right side) and a higher incidence of cerebral infarction. Age, extension of the RICA dissection and LVEF impairment are independent risk factors for AAD‐related death.
    Type of Medium: Online Resource
    ISSN: 0742-2822 , 1540-8175
    URL: Issue
    URL: Article
    DOI: 10.1111/echo.v39.8
    DOI: 10.1111/echo.15426
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2041033-5
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  • 9
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    A new-generation sand and dust storm forecasting system GRAPES_CUACE/Dust: Model development, verification and numerical simulation
    Springer Science and Business Media LLC ; 2010
    In:  Chinese Science Bulletin Vol. 55, No. 7 ( 2010-3), p. 635-649
    Details
    In: Chinese Science Bulletin, Springer Science and Business Media LLC, Vol. 55, No. 7 ( 2010-3), p. 635-649
    Type of Medium: Online Resource
    ISSN: 1001-6538 , 1861-9541
    URL: Article
    DOI: 10.1007/s11434-009-0481-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2069521-4
    detail.hit.zdb_id: 2816140-3
    SSG: 11
    SSG: 6,25
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  • 10
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    Interferon Regulatory Factor 7 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Hypertension Vol. 63, No. 4 ( 2014-04), p. 713-722
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 63, No. 4 ( 2014-04), p. 713-722
    Abstract: Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding–induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload–induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II–induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBα S32A/S36A super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-β S177E/S181E (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.113.02653
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 2094210-2
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