• Title/Summary/Keyword: cardiac differentiation

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Expression of β-arrestin 1 in Gastric Cardiac Adenocarcinoma and its Relation with Progression

  • Wang, Li-Guang;Su, Ben-Hua;Du, Jia-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5671-5675
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    • 2012
  • Objective: Arrestins act as mediators of G protein-coupled receptor (GPCR) desensitization and trafficking, also actin as a scaffold for many intracellular signaling network. The role that ${\beta}$-arrestin 1 plays in gastric cardiac adenocarcinoma (GCA) and its clinicopathologic significance are untouched. Methods: Fifty patients with gastric cardiac adenocarcinoma were retrospectively enrolled and ${\beta}$-arrestin 1 was detected using immunohistochemistry in tissue samples. Results: Nuclear expression of ${\beta}$-arrestin 1 was observed in 78% of GCA samples (39/50) and cytoplasmic expression in 70% (35/50). ${\beta}$-arrestin 1 could be found in both nucleus and cytoplasm of 54% GCA (27/50) or in either of them in 94% (47/50). ${\beta}$-arrestin 1 protein positivity in well/moderately differentiated carcinomas was significantly higher than that in poorly differentiated carcinomas (P=0.005). We found increased expression of ${\beta}$-arrestin 1 in cytoplasm was correlated with lymph nodal metastasis (P=0.002) and pathological lymph nodal staging (P=0.030). We also found ${\beta}$-arrestin 1 to be over-expressed in glandular epithelia cells of mucinous adenocarcinoma, a tumour type associated with an adverse outcome of gastric cardiac adenocarcinoma (P=0.022). Conclusion: ${\beta}$-arrestin 1 is over-expressed in the nucleus and/or cytoplasm of gastric cardiac adenocarcinoma. However, ${\beta}$-arrestin 1 has no relationship with the prognosis of gastric cardiac adenocarcinoma (P>0.05). Our data imply that ${\beta}$-arrestin 1 in cytoplasm may be involved in differentiation and metastasis of gastric cardiac adenocarcinoma.

Expression of CDX2 and Villin in Gastric Cardiac Intestinal Metaplasia and the Relation with Gastric Cardiac Carcinogenesis

  • Xiao, Zhong-Yue;Ru, Yi;Sun, Jiang-Tao;Gao, She-Gan;Wang, Yu-Feng;Wang, Li-Dong;Feng, Xiao-Shan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.247-250
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    • 2012
  • Objective: To determine whether CDX2 and villin protein expression are associated with intestinal metaplasia (IM) in gastric cardiac mucosa and to explore the relationship with evolution of gastric cardiac adenocarcinoma (GCA). Methods: We studied 143 gastric cardiac biopsy or resection specimens from Henan province China, including 25 cardiac gastritis specimens with IM, 65 dysplasia specimens with IM and 35 gastric cardiac adenocarcinoma specimens and stained them for CDX2 and villin by the immunohistochemical SP method. 15 normal gastric cardiac biopsy specimens were also collected as control. Results: (1) Normal gastric mucosa presented no CDX2 and villin expression. The positive rates of CDX2 protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissues were 84.0% (21/25), 66.7% (32/48) and 36.4% (20/55), respectively. While the positive rates of villin protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissues were 76.0% (19/25), 70.8% (34/48) and 45.5% (25/55), respectively. There were significant differences among the three groups for both CDX2 and villin (P<0.01). Spearman's rank correlation coefficient(rho) showed a close correlation between the two proteins (r=0.843, P<0.01) and both were positively related with tumor differentiation (both P<0.05), but not associated with age, sex, invasion and metastasis of lymph node (P>0.05). Conclusion: Our results suggest that ectopic expression of CDX2 and villin may be involved in early-stage IM and tumorigenesis in gastric cardia and the expression of villin may be regulated by CDX2.

Differential Diagnosis of Thick Myocardium according to Histologic Features Revealed by Multiparametric Cardiac Magnetic Resonance Imaging

  • Min Jae Cha;Cherry Kim;Chan Ho Park;Yoo Jin Hong;Jae Min Shin;Tae Hoon Kim;Yoon Jin Cha;Chul Hwan Park
    • Korean Journal of Radiology
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    • v.23 no.6
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    • pp.581-597
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    • 2022
  • Left ventricular (LV) wall thickening, or LV hypertrophy (LVH), is common and occurs in diverse conditions including hypertrophic cardiomyopathy (HCM), hypertensive heart disease, aortic valve stenosis, lysosomal storage disorders, cardiac amyloidosis, mitochondrial cardiomyopathy, sarcoidosis and athlete's heart. Cardiac magnetic resonance (CMR) imaging provides various tissue contrasts and characteristics that reflect histological changes in the myocardium, such as cellular hypertrophy, cardiomyocyte disarray, interstitial fibrosis, extracellular accumulation of insoluble proteins, intracellular accumulation of fat, and intracellular vacuolar changes. Therefore, CMR imaging may be beneficial in establishing a differential diagnosis of LVH. Although various diseases share LV wall thickening as a common feature, the histologic changes that underscore each disease are distinct. This review focuses on CMR multiparametric myocardial analysis, which may provide clues for the differentiation of thickened myocardium based on the histologic features of HCM and its phenocopies.

In Vitro Differentiated Functional Cardiomyocytes from Parthenogenetic Mouse Embryonic Stem Cells (단위발생유래 생쥐 배아줄기세포로부터 체외 분화된 기능성 심근세포)

  • Shin Hyun-Ah;Kim Eun-Young;Lee Keum-Sil;Cho Hwang-Yun;Lee Won-Don;Park Se-Pill;Lim Jin-Ho
    • Reproductive and Developmental Biology
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    • v.30 no.1
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    • pp.47-52
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    • 2006
  • This study was conducted to examine whether the parthenogenetic mouse embryonic stem (P-mES) cells can differentiate into functional cardiomyocytes in vitro similar to (mES) cells. p-mES04 and IVF-derived mES03 cells were cultured by suspension culture for 4 days. The formed embryoid bodies (EBs) were treated with 0.75% dimethyl-sulfoxide (DMSO) for further 4 days (4-/4+), and then plated onto gelatin coated culture dish. The appearance of contracting cardiomyocytes from the P-mES04 and mES03 cells was examined for 30 days. The highest cumulative frequency was detected at days 13 (69.83%) and 22 (61.3%), respectively. By immunocytochemistry, beating P-mES04 cells were positively stained with muscle specific anti-sarcomeric a-actinin Ab and cardiac specific anti-cardiac troponin I Ab similar to contracted mES03 cells. When the expression of cardiac muscle-specific genes was analyzed by RT-PCR, beating P-mES04 cells were expressed cardiac specific L-type calcium channel, a1C, cardiac myosin heavy chain a, cardiac muscle heavy polypeptide $7{\beta}$, GATA binding protein 4 and atrial natriuretic factor, but not expressed skeletal muscle specific L-type calcium channel, a1S, which was similar to male adult heart cells and mES03-derived beating cardiomyocytes. The result demonstrates that the P-mES cells can be used as an alternative for the study on the characteristic analysis of in vitro cardiomyocyte differentiation from the ES cells.

Establishment of Mouse Embryonic Stem Cell and Effects of Herbal Medicine on Induction of Cardiomyocyte Differentiation

  • Lee, Ji Hyang;Lee, Eun
    • Korean Journal of Plant Resources
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    • v.25 no.6
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    • pp.693-699
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    • 2012
  • This study was conducted to investigate the effects of Woohwangcheungsimweun (ox bezoar), deer antlers, and wild ginseng on induction of cardiomyocyte differentiation using the established mouse embryonic stem (ES) cells. The expression of atrial natriuretic peptide (ANP) was highest in Woohwangcheungsimweun treatment group. The expression of rabbit anti-GATA-4(GATA-4) and troponin (TnI) were highest in wild ginseng and Woohwangcheungsimweun treatment groups, respectively. Fluorescence activated cell sorting (FACS) analysis showed that the expression of ANP was highest in Dimethyl sulfoxide(DMSO) and Woohwangcheungsimweun treatment groups. The expression of GATA-4 was relatively high in wild ginseng treatment group. The expression of TnI was highest in Woohwangcheungsimweun treatment group. In the gene expression analysis, DMSO greatly inhibited GATA-4 expression to 25% of control. Woohwangcheungsimweun treatment caused to increase cTnI and cardiac ANP expression significantly. Wild ginseng extract upregulated GATA-4 gene expression. In conclusion, DMSO widely used as cardiomyocyte differentiation inducer did not show significant effects on the expression of ANP, GATA-4 and TnI in this study. Woohwangcheungsimweun showed upregulation of ANP and TnI expression. Wild ginseng extract showed greater effects than DMSO on GATA-4 expression. These results might suggest that the combination of Woohwangcheungsimweun and wild ginseng extract treatment can be expected to increase expressions of all three genes.

Kinetic Properties of Extracted Lactate Dehydrogenase and Creatine Kinase from Mouse Embryonic Stem Cell- and Neonatal-derived Cardiomyocytes

  • Zonouzi, Roseata;Ashtiani, Saeid Kazemi;Hosseinkhani, Saman;Baharvand, Hossein
    • BMB Reports
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    • v.39 no.4
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    • pp.426-431
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    • 2006
  • Embryonic stem cells (ESCs), representing a population of undifferentiated pluripotent cells with both self-renewal and multilineage differentiation characteristics, are capable of spontaneous differentiation into cardiomyocytes. The present study sought to define the kinetic characterization of lactate dehydrogenase (LDH) and creatine kinase (CK) of ESC- and neonatal-derived cardiomyocytes. Spontaneously differentiated cardiomyocytes from embryoid bodies (EBs) derived from mouse ESC line (Royan B1) and neonatal cardiomyocytes were dispersed in a buffer solution. Enzymes were extracted by sonication and centrifugation for kinetic evaluation of LDH and CK with spectrophotometric methods. While a comparison between the kinetic properties of the LDH and CK of both groups revealed not only different Michaelis constants and optimum temperatures for LDH but also different Michaelis constants and optimum pH for CK, the pH profile of LDH and optimum temperature of CK were similar. In defining some kinetic properties of cardiac metabolic enzymes of ESC-derived cardiomyocytes, our results are expected to further facilitate the use of ESCs as an experimental model.

Neuregulin-1 promotes cardiomyocyte differentiation of genetically engineered embryonic stem cell clones

  • Wang, Zhi;Xu, Guotong;Wu, Yalan;Liu, Shaowen;Sun, Baogui;Dai, Qiuyan
    • BMB Reports
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    • v.41 no.10
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    • pp.699-704
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    • 2008
  • Embryonic stem (ES) cell-derived cardiomyocytes (ESCMs) must be specifically purified in order to prevent teratoma formation, and this confusing issue has hampered their clinical application. We therefore investigated a technique to generate pure labeled ESCMs for possible use in cardiac repair. We generated transgenic ES cell lines expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of the $\alpha$-cardiac myosin heavy chain ($\alpha$-MHC) promoter. Differentiated EGFP-positive ES cells displayed characteristics of CMs. Furthermore, neuregulin-1 (NRG-1) upregulated the expression of the cardiac-restricted transcription factors Nkx2.5 and GATA-4, as well as differentiated CM factors ($\alpha$-MHC, $\beta$-MHC). Immunohistochemistry demonstrated that NRG-1 increased expression of cardiac-specific troponin T in the beating foci of the embryoid bodies. This work revealed a potential method for specifically labeling and enriching ESCMs by combining genetically-engineered ES cell clones and exogenous growth factor treatment.

Identification and Characterization of Secreted Phosphoprotein 2 as a Novel Bioactive Protein for Myocardial Differentiation (심근세포로의 분화에 관여하는 새로운 생리활성 단백질 SPP2의 발굴)

  • Sejin Jeon
    • Journal of Life Science
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    • v.33 no.1
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    • pp.64-72
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    • 2023
  • Despite several advances in identification of cardiac transcription factors, there are still needs to find new bioactive molecules that promote cardiomyogenesis from stem cells to highly efficient myocardial differentiation. We analyzed Illumina expression microarray data of mouse embryonic stem cells (mESCs)-derived cardiomyocytes. 276 genes were upregulated (≥ 4fold) in mESCs-derived cardiomyocytes compared undifferentiated ESCs. Secreted phosphoprotein 2 (Spp2) is one of candidates and is known to inhibit bone morphogenetic protein 2 (BMP2) signal transduction as a pseudoreceptor for BMP2. However, its function in cardiomyogenesis is unknown. We confirmed that Spp2 expression increased during the differentiation into functional cardiomyocytes using mESCs, TC-1/Kh2 and E14. Interestingly, Spp2 secretion transiently increased 3 days after formation of embryoid bodies (EBs), indicating that the extracellular secretion of Spp2 is involved in the differentiation of ESCs into cardiomyocytes. To characterize Spp2, we performed experiments using the C2C12 mouse myoblast cell line, which has the property of shifting the differentiation pathway from myoblastic to osteoblastic by treatment with BMP2. Similar to the differentiation of ESCs, transcription of Spp2 increased as C2C12 myoblasts differentiated into myotubes. In particular, Spp2 secretion increased dramatically in the early stage of differentiation. Furthermore, treatment with Spp2-Flag recombinant protein promoted the differentiation of C2C12 myoblasts into myotubes. Taken together, we suggest a novel bioactive protein Spp2 that differentiates ESCs into cardiomyocytes. This may be useful for understanding the molecular pathways of cardiomyogenesis and for experimental or clinical promotion of stem cell therapy for ischemic heart diseases.

The Effects of an Advanced Cardiac Life Support Simulation Training Based on the Mastery Learning Model (완전학습 모델을 기반으로 한 시뮬레이션 훈련이 전문심장소생술 습득에 미치는 효과)

  • Kwon, Eun Ok;Shim, Mi Young;Choi, Eun Ha;Lim, Sang Hee;Han, Kyoung Min;Lee, Eun Joon;Chang, Sun Ju;Lee, Mi Mi
    • Journal of Korean Clinical Nursing Research
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    • v.18 no.1
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    • pp.126-135
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    • 2012
  • Purpose: This study was aimed to develop a simulation training program of an advanced cardiac life support (ACLS) based on the mastery learning model (Simulation-MLM), and evaluate the effects of the program on critical care nurses. Methods: As an experimental pre-post test with a non-equivalent control group, the study employed convenience sampling of 38 critical care nurses. The experimental group received the Simulation-MLM including a theoretical lecture, formative evaluation, and simulation training, whereas only a theoretical lecture for the control group. The knowledge, self-efficacy, and performance degrees of respondents were measured to verify the effects of the Simulation-MLM. The statistical processing of the collected data utilized the SPSS WIN 17.0 program. Results: After receiving Simulation-MLM, the participants in the experimental group reported higher marks in the knowledge, self-efficacy and performance of ACLS compared with those in the control group. However, both experimental and control groups demonstrated no significant differences in knowledge, self-efficacy and performance. Conclusion: Despite of the limitation of a small sample size, this study was considered meaningful in a sense that it showed a venue for improving ACLS training efficiency. Future research with more distinct treatment differentiation and better adequate outcome variables was warranted in order to prove the effects of a theory-based simulation education.