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  • Ovid Technologies (Wolters Kluwer Health)  (12)
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  • Ovid Technologies (Wolters Kluwer Health)  (12)
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  • 1
    In: Circulation: Cardiovascular Imaging, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 4 ( 2012-07), p. 481-490
    Abstract: Human cardiac progenitor cells have demonstrated great potential for myocardial repair in small and large animals, but robust methods for longitudinal assessment of their engraftment in humans is not yet readily available. In this study, we sought to optimize and evaluate the use of positron emission tomography (PET) reporter gene imaging for monitoring human cardiac progenitor cell (hCPC) transplantation in a mouse model of myocardial infarction. Methods and Results— hCPCs were isolated and expanded from human myocardial samples and stably transduced with herpes simplex virus thymidine kinase (TK) PET reporter gene. Thymidine kinase-expressing hCPCs were characterized in vitro and transplanted into murine myocardial infarction models (n=57). Cardiac echocardiographic, magnetic resonance imaging and pressure-volume loop analyses revealed improvement in left ventricular contractile function 2 weeks after transplant (hCPC versus phosphate-buffered saline, P 〈 0.03). Noninvasive PET imaging was used to track hCPC fate over a 4-week time period, demonstrating a substantial decline in surviving cells. Importantly, early cell engraftment as assessed by PET was found to predict subsequent functional improvement, implying a “dose–effect” relationship. We isolated the transplanted cells from recipient myocardium by laser capture microdissection for in vivo transcriptome analysis. Our results provide direct evidence that hCPCs augment cardiac function after their transplantation into ischemic myocardium through paracrine secretion of growth factors. Conclusions— PET reporter gene imaging can provide important diagnostic and prognostic information regarding the ultimate success of hCPC treatment for myocardial infarction.
    Type of Medium: Online Resource
    ISSN: 1941-9651 , 1942-0080
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 2440475-5
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  • 2
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 68, No. 5 ( 2018-11), p. 1865-1878
    Abstract: Cluster of differentiation 97 (CD97) is a member of the epidermal growth factor seven‐transmembrane family belonging to the class B G protein–coupled receptors (GPCRs). The protein affects tumor aggressiveness through its cellular ligand CD55 stimulation and exhibits adhesive properties. Studies have demonstrated the involvement of CD97 in dedifferentiation, migration, invasiveness, and metastasis of tumors. However, little information is currently available on the specific role of CD97 in hepatocellular carcinoma (HCC). Here, we have shown that CD97 up‐regulation in HCCs is positively correlated with tumor metastasis. Functionally, CD97 promoted cell migration and invasion in vitro . In an in vivo mouse model, overexpression of CD97 in HCC cells led to accelerated lung metastasis. Mechanistically, CD97 cooperated with the altered regulator, GPCR kinase 6 (GRK6), to mediate GPCR desensitization and internalization. Down‐regulation of GRK6 suppressed CD97 internalization and promoted CD97 expression. Integrated regulatory interactions between CD97 and GRK6 stimulated downstream matrix metalloproteinase 2/9 secretion and, consequently, HCC metastasis. Conclusion: Our collective findings support the utility of CD97 as an effective potential prognosticator and therapeutic target for HCC.
    Type of Medium: Online Resource
    ISSN: 0270-9139 , 1527-3350
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1472120-X
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  • 3
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 46 ( 2022-11-18), p. e31810-
    Type of Medium: Online Resource
    ISSN: 1536-5964
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2049818-4
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  • 4
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Journal of the American Society of Nephrology Vol. 34, No. 11S ( 2023-11), p. 298-298
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 11S ( 2023-11), p. 298-298
    Type of Medium: Online Resource
    ISSN: 1046-6673
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2029124-3
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  • 5
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 121, No. suppl_1 ( 2017-07-21)
    Abstract: Introduction: The injured heart undergoes a major process of cellular apoptosis in the initial stage of MI, therefore, the most fundamental method to prevent post-MI remodeling is to suppress cardiomyocyte apoptosis. In this study, we have illustrated the key role of long noncoding RNA, Maternally expressed gene 3 ( Meg3 ), on cardiomyocyte apoptosis and the underlying mechanisms in heart. Methods: Neonatal murine cardiomyocytes and human ESC-derived cardiomyocytes were subjected to hypoxia, and cellular apoptosis was evaluated with Annexin V assay. The Meg3 regulation by p53 was measured by luciferase reporter assay. The complex of Meg3 and RNA-binding protein FUS (Fused in sarcoma) was determined by EMSA and RIP. Adeno-Associated Virus serotype 9 (AAV9) system was employed to knock down Meg3 in cardiomyocytes in vivo, and the cardiac function was evaluated by echocardiography and ex-vivo assays. Results: We first found that Meg3 was progressively upregulated in the murine injured heart after MI, and it showed the pro-apoptotic functions in primary cardiomyocytes. Meg3 could be directly upregulated by p53 during hypoxia condition, and was involved in apoptotic regulation via its direct binding with FUS. The Meg3 knockdown in cardiomyocytes by AAV9 system could preserve heart function in murine myocardial infarction. Moreover, its pro-apoptotic function was conserved in human cardiomyocytes. Conclusion: Together, these results indicate that p53-induced Meg3 - FUS complex plays an important role on cardiomyocyte apoptosis post-MI, and its specific knockdown in cardiomyocytes with AAV9 system represents a promising method to treat myocardial infarction.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467838-X
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  • 6
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 11 ( 2022-03-18)
    Abstract: Heart failure with preserved ejection fraction (HFpEF) comprises about 50% of the cases of heart failure (HF), but so far there is no effective treatment strategy. This study used bibliometric methods to analyze the scientific literature on HFpEF in 2009 to 2020, and evaluate the global scientific output of HFpEF research, in order to explore the research status and trends in this field. Methods: Documents about the HFpEF research published in 2009 to 2020 were retrieved from Science Citation Index Expanded (SCIE) in Web of Science. This study used bibliometrix R-package, VOSviewer, and CiteSpace to conduct the bibliometric analysis. Results: A total of 1971 documents (1508 articles and 283 reviews) were retrieved to construct the local HFpEF literature collection for analysis. The number of annual documents had increased year by year in general, from 24 to 353. Relevant documents were mainly written in English, and mostly focused on the field of “Cardiovascular System Cardiology.” USA ranked first in the relevant countries/regions with most documents, and the leading affiliation was Mayo Clin. Shah SJ was the most productive author, while Borlaug BA ranked highest among the local cited authors and G-index. Circulation was the most local cited source, while Eur J Heart Fail published the most documents and was rated as the top source in terms of G-index. “Paulus WJ, 2013, J Am Coll Cardiol” was the top local cited document within the local HFpEF literature collection, while “Owan TE, 2006, New Engl J Med” outside the local HFpEF literature collection was the most local cited reference. The keywords such as “mortality,” “dysfunction,” “diagnosis,” “outcomes,” and “diastolic dysfunction” were most frequent, while “hemodynamics,” “comorbidity,” “myocardial infarction,” “inflammation,” and “phenotype” indicated research frontiers or emerging trends. Furthermore, this study also found some deeper bibliometric relationships through bibliographic networks. Conclusions: Due to the multi-dimensional bibliometric analysis, this study shows a wide view of scientific productivity related to HFpEF, and provides valuable guidance for researchers interested in HFpEF, assisting them in understanding the research status, identifying potential collaborators, discovering research hotspots and frontiers, and conducting more in-depth research.
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2049818-4
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  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2024
    In:  Circulation Research Vol. 134, No. 3 ( 2024-02-02), p. 290-306
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 134, No. 3 ( 2024-02-02), p. 290-306
    Abstract: Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disorder. However, the pathogenesis of HCM, especially its nongenetic mechanisms, remains largely unclear. Transcription factors are known to be involved in various biological processes including cell growth. We hypothesized that SP1 (specificity protein 1), the first purified TF in mammals, plays a role in the cardiomyocyte growth and cardiac hypertrophy of HCM. METHODS: Cardiac-specific conditional knockout of Sp1 mice were constructed to investigate the role of SP1 in the heart. The echocardiography, histochemical experiment, and transmission electron microscope were performed to analyze the cardiac phenotypes of cardiac-specific conditional knockout of Sp1 mice. RNA sequencing, chromatin immunoprecipitation sequencing, and adeno-associated virus experiments in vivo were performed to explore the downstream molecules of SP1. To examine the therapeutic effect of SP1 on HCM, an SP1 overexpression vector was constructed and injected into the mutant allele of Myh6 R404Q/+ ( Myh6 c. 1211C 〉 T) HCM mice. The human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) from a patient with HCM were used to detect the potential therapeutic effects of SP1 in human HCM. RESULTS: The cardiac-specific conditional knockout of Sp1 mice developed a typical HCM phenotype, displaying overt myocardial hypertrophy, interstitial fibrosis, and disordered myofilament. In addition, Sp1 knockdown dramatically increased the cell area of hiPSC-CMs and caused intracellular myofibrillar disorganization, which was similar to the hypertrophic cardiomyocytes of HCM. Mechanistically, Tuft1 was identified as the key target gene of SP1. The hypertrophic phenotypes induced by Sp1 knockdown in both hiPSC-CMs and mice could be rescued by TUFT1 (tuftelin 1) overexpression. Furthermore, SP1 overexpression suppressed the development of HCM in the mutant allele of Myh6 R404Q/+ mice and also reversed the hypertrophic phenotype of HCM hiPSC-CMs. CONCLUSIONS: Our study demonstrates that SP1 deficiency leads to HCM. SP1 overexpression exhibits significant therapeutic effects on both HCM mice and HCM hiPSC-CMs, suggesting that SP1 could be a potential intervention target for HCM.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467838-X
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Journal of the American Society of Nephrology Vol. 34, No. 11S ( 2023-11), p. 172-172
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 11S ( 2023-11), p. 172-172
    Type of Medium: Online Resource
    ISSN: 1046-6673
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2029124-3
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  • 9
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Stroke Vol. 48, No. 8 ( 2017-08), p. 2255-2262
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. 8 ( 2017-08), p. 2255-2262
    Abstract: Intracerebral hemorrhage (ICH) is a neurologically destructive stroke, for which no valid treatment is available. This preclinical study examined the therapeutic effect of PD-L1 (programmed death ligand 1), a B7 family member and a ligand for both PD-1 (programmed death 1) and B7-1 (CD80), in a murine ICH model. Methods— ICH was induced by injecting autologous blood into 252 male C57BL/6 and Rag1 −/− mice. One hour later, ICH mice were randomly assigned to receive an intraperitoneal injection of vehicle, PD-L1, or anti–PD-L1 antibody. Neurological function was assessed along with brain edema, brain infiltration of immune cells, blood–brain barrier integrity, neuron death, and mTOR (mammalian target of rapamycin) pathway products. Results— PD-L1 significantly attenuated neurological deficits, reduced brain edema, and decreased hemorrhage volume in ICH mice. PD-L1 specifically downsized the number of brain-infiltrating CD4 + T cells and the percentages of Th1 and Th17 cells but increased the percentages of Th2 and regulatory T cells. In the PD-L1–treated group, we observed an amelioration of the inflammatory milieu, decreased cell death, and enhanced blood–brain barrier integrity. PD-L1 also inhibited the mTOR pathway. The administration of anti–PD-L1 antibody produced the opposite effects to those of PD-L1 in ICH mice. Conclusions— PD-L1 provided protection from the damaging consequences of ICH.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467823-8
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. 7 ( 2016-07), p. 1899-1906
    Abstract: Preclinical studies and a proof-of-concept clinical study have shown that sphingosine-1-phosphate receptor (S1PR) modulator, fingolimod, improves the clinical outcome of intracerebral hemorrhage (ICH). However, the specific subtype of the S1PRs through which immune modulation provides protection in ICH remains unclear. In addition, fingolimod-induced adverse effects could limit its use in patients with stroke because of interactions with other S1PR subtypes, particularly with S1PR3. RP101075 is a selective S1PR1 agonist with superior cardiovascular safety profile. In this study, we investigated the impact of RP101075 treatment in a mouse model of ICH. Methods— ICH was induced by injection of autologous blood in 294 male C57BL/6J and Rag2 −/− mice. ICH mice randomly received vehicle, RP101075, or RP101075 plus S1PR1 antagonist W146 by daily oral gavage for three consecutive days, starting from 30 minutes after surgery. Neurodeficits, brain edema, brain infiltration of immune cells, blood–brain barrier integrity, and cell death were assessed after ICH. Results— RP101075 significantly attenuated neurological deficits and reduced brain edema in ICH mice. W146 blocked the effects of RP101075 on neurodeficits and brain edema. RP101075 reduced the counts of brain-infiltrating lymphocytes, neutrophils, and microglia, as well as cytokine expression after ICH. Enhanced blood–brain barrier integrity and alleviated neuronal death were also seen in ICH mice after RP101075 treatment. Conclusions— S1PR1 modulation via RP101075 provides protection in experimental ICH. Together with the advantageous pharmacological features of RP101075, these results warrant further investigations of its mechanisms of action and translational values in ICH patients.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467823-8
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