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1.
J Cardiothorac Surg ; 19(1): 153, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532449

RESUMO

BACKGROUND: The Cabrol procedure has undergone various modifications and developments since its invention. However, there is a notable gap in the literature regarding meta-analyses assessing it. METHODS: A systematic review and meta-analysis was conducted to evaluate the effectiveness and long-term outcomes of the Cabrol procedure and its modifications. Pooling was conducted using random effects model. Outcome events were reported as linearized occurrence rates (percentage per patient-year) with 95% confidence intervals. RESULTS: A total of 14 studies involving 833 patients (mean age: 50.8 years; 68.0% male) were included in this meta-analysis. The pooled all-cause early mortality was 9.0% (66 patients), and the combined rate of reoperation due to bleeding was 4.9% (17 patients). During the average 4.4-year follow-up (3,727.3 patient-years), the annual occurrence rates (linearized) for complications were as follows: 3.63% (2.79-4.73) for late mortality, 0.64% (0.35-1.16) for aortic root reoperation, 0.57% (0.25-1.31) for hemorrhage events, 0.66% (0.16-2.74) for thromboembolism, 0.60% (0.29-1.26) for endocarditis, 2.32% (1.04-5.16) for major valve-related adverse events, and 0.58% (0.34-1.00) for Cabrol-related coronary graft complications. CONCLUSION: This systematic review provides evidence that the outcomes of the Cabrol procedure and its modifications are acceptable in terms of mortality, reoperation, anticoagulation, and valve-related complications, especially in Cabrol-related coronary graft complications. Notably, the majority of Cabrol procedures were performed in reoperations and complex cases. Furthermore, the design and anastomosis of the Dacron interposition graft for coronary reimplantation, considering natural anatomy and physiological hemodynamics, may promise future advancements in this field.


Assuntos
Cardiopatias , Próteses Valvulares Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Prótese Vascular , Valva Aórtica/cirurgia , Aorta/cirurgia , Reoperação , Cardiopatias/cirurgia
2.
Front Cardiovasc Med ; 9: 913776, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531717

RESUMO

Background: Although advanced surgical and interventional treatments are available for advanced aortic valve calcification (AVC) with severe clinical symptoms, early diagnosis, and intervention is critical in order to reduce calcification progression and improve patient prognosis. The aim of this study was to develop therapeutic targets for improving outcomes for patients with AVC. Materials and methods: We used the public expression profiles of individuals with AVC (GSE12644 and GSE51472) to identify potential diagnostic markers. First, the R software was used to identify differentially expressed genes (DEGs) and perform functional enrichment analysis. Next, we combined bioinformatics techniques with machine learning methodologies such as random forest algorithms and support vector machines to screen for and identify diagnostic markers of AVC. Subsequently, artificial neural networks were employed to filter and model the diagnostic characteristics for AVC incidence. The diagnostic values were determined using the receiver operating characteristic (ROC) curves. Furthermore, CIBERSORT immune infiltration analysis was used to determine the expression of different immune cells in the AVC. Finally, the CMap database was used to predict candidate small compounds as prospective AVC therapeutics. Results: A total of 78 strong DEGs were identified. The leukocyte migration and pid integrin 1 pathways were highly enriched for AVC-specific DEGs. CXCL16, GPM6A, BEX2, S100A9, and SCARA5 genes were all regarded diagnostic markers for AVC. The model was effectively constructed using a molecular diagnostic score system with significant diagnostic value (AUC = 0.987) and verified using the independent dataset GSE83453 (AUC = 0.986). Immune cell infiltration research revealed that B cell naive, B cell memory, plasma cells, NK cell activated, monocytes, and macrophage M0 may be involved in the development of AVC. Additionally, all diagnostic characteristics may have varying degrees of correlation with immune cells. The most promising small molecule medicines for reversing AVC gene expression are Doxazosin and Terfenadine. Conclusion: It was identified that CXCL16, GPM6A, BEX2, S100A9, and SCARA5 are potentially beneficial for diagnosing and treating AVC. A diagnostic model was constructed based on a molecular prognostic score system using machine learning. The aforementioned immune cell infiltration may have a significant influence on the development and incidence of AVC.

3.
Med Sci Monit ; 26: e925388, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32780729

RESUMO

BACKGROUND The protein NKX2-5 affects mammalian heart development. In mice, the disruption of Nkx2-5 has been associated with arrhythmias, abnormal myocardial contraction, abnormal cardiac morphogenesis, and death. However, the details of the mechanisms are unclear. This study was designed to investigate them. MATERIAL AND METHODS Rat cardiomyocytes from the H9c2 cell line were used in our study. First, we knocked down Nkx2-5 in the H9c2 cells and then validated consequent changes in cell proliferation and migration. We then used RNA sequencing to determine the changes in transcripts. Finally, we validated these results by quantitative reverse transcription-polymerase chain reaction. RESULTS We confirmed that Nkx2-5 regulates the proliferation and migration of H9c2 cells. In our experiments, Nkx2-5 regulated the expression of genes related to proliferation, migration, heart development, and disease. Based on bioinformatics analysis, knockdown of Nkx2-5 caused differential expression of genes involved in cardiac development, calcium ion-related biological activity, the transforming growth factor (TGF)-ß signaling pathway, pathways related to heart diseases, the MAPK signaling pathway, and other biological processes and signaling pathways. CONCLUSIONS Nkx2-5 may regulate proliferation and migration of the H9c2 cells through the genes Tgfb-2, Bmp10, Id2, Wt1, Hey1, and Cacna1g; rno-miR-1-3p; the TGF­ß signaling pathway; the MAPK signaling pathway; as well as other genes and pathways.


Assuntos
Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Proteína Homeobox Nkx-2.5/fisiologia , Miócitos Cardíacos/citologia , Animais , Linhagem Celular , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Proteína Homeobox Nkx-2.5/genética , Miócitos Cardíacos/metabolismo , RNA Mensageiro/genética , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
4.
Stem Cell Res ; 42: 101687, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31869684

RESUMO

The human induced pluripotent stem cell (iPSC) line YAHKMUi001-A was derived from the dermal fibroblasts of a patient with Tetralogy of Fallot (TOF), with a mutation in the TBX1 gene (c.928G > A). The skin fibroblasts were obtained from a 4-year-old boy, and were infected with Sendai virus expressing the Yamanaka factors. The YAHKMUi001-A iPSC line expresses pluripotent stem cell markers, displays a normal karyotype, and has the capacity to differentiate into 3 germ layers. This cell line model can be a good tool to study the pathological mechanism of the TBX1 gene mutations associated with TOF.


Assuntos
Células-Tronco Pluripotentes Induzidas/metabolismo , Proteínas com Domínio T/metabolismo , Tetralogia de Fallot/genética , Diferenciação Celular , Linhagem Celular , Reprogramação Celular , Pré-Escolar , Humanos , Masculino , Mutação
5.
Med Sci Monit ; 25: 2756-2763, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30982828

RESUMO

BACKGROUND The NKX2 gene family is made up of core transcription factors that are involved in the morphogenesis of the vertebrate heart. NKx2-5 plays a pivotal role in mouse cardiogenesis, and mutations in NKx2-5 result in an abnormal structure and function of the heart, including atrial septal defect and cardiac electrophysiological abnormalities. MATERIAL AND METHODS To investigate the genetic variation of NKX2-5 in Chinese patients with sporadic atrial septal defect, we sequenced the full length of the NKX2-5 gene in the participants of the study. Four hundred thirty-nine patients and 567 healthy unrelated individuals were recruited. Genomic DNA was extracted from the peripheral blood leukocytes of the participants. DNA samples from the participants were amplified by multiplex PCR and sequenced on an Illumina HiSeq platform. Variations were detected by comparison with a standard reference genome and annotation with a variant effect predictor. RESULTS Thirty variations were detected in Chinese patients with sporadic atrial septal defect, and 6 single nucleotide polymorphisms (SNPs) had a frequency greater than 1%. Among the 30 variations, the SNPs rs2277923 and rs3729753 were extremely prominent, with a high frequency and odds ratio in patients. CONCLUSIONS Single nucleotide variations are the prominent genetic variations of NKX2-5 in Chinese patients with sporadic atrial septal defect. The SNPs rs2277923 and rs3729753 are prominent single nucleotide variations (SNVs) in Chinese patients with sporadic atrial septal defect.


Assuntos
Comunicação Interatrial/genética , Proteína Homeobox Nkx-2.5/genética , Povo Asiático/genética , Sequência de Bases , China/epidemiologia , Análise Mutacional de DNA , Feminino , Genes Homeobox , Comunicação Interatrial/sangue , Comunicação Interatrial/epidemiologia , Comunicação Interatrial/metabolismo , Proteína Homeobox Nkx-2.5/sangue , Proteína Homeobox Nkx-2.5/metabolismo , Humanos , Masculino , Mutação , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Fatores de Transcrição/genética
6.
Med Sci Monit ; 24: 1340-1358, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29505555

RESUMO

BACKGROUND Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. MATERIAL AND METHODS Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. RESULTS From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (P<0.05); variants in FOXL2 and MYH6 were found in patients with isolated, sporadic ASD (P<5×10^-4). CONCLUSIONS This was the first study that demonstrated variants in FOXL2 and HYDIN associated with sporadic ASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations.


Assuntos
Povo Asiático/genética , Comunicação Interatrial/genética , Adulto , Miosinas Cardíacas/genética , Miosinas Cardíacas/metabolismo , China , Biologia Computacional/métodos , Exoma , Éxons , Feminino , Proteína Forkhead Box L2/genética , Proteína Forkhead Box L2/metabolismo , Predisposição Genética para Doença , Variação Genética , Humanos , Masculino , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Mutação , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Análise de Sequência de DNA/métodos , Sequenciamento do Exoma/métodos
7.
Gene ; 575(2 Pt 1): 303-12, 2016 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-26375510

RESUMO

Congenital heart disease (CHD) is one of most common birth defects, causing fetal loss and death in newborn all over the world. Atrial and ventricular septal defects were the most common CHD subtypes in most districts. During the past decades, several genes were identified to control atrial septum formation, and mutations of these genes can cause cardiac septation defects. However, the pathogenic mechanism of ASD on transcriptional levels has not been well elucidated yet. Herein, we performed comparative transcriptome analysis between normal and atrial septal defect (ASD) patients by Illumina RNA sequencing (RNA-seq). Advanced bioinformatic analyses were employed to identify dysregulated genes in ASD. The results indicated that cardiac specific transcriptional factors (GATA4 and NKX2-5), extracellular signal molecules (VEGFA and BMP10) and cardiac sarcomeric proteins (MYL2, MYL3, MYH7, TNNT1 and TNNT3) were downregulated in ASD which may affect heart atrial septum formation, cardiomyocyte proliferation and cardiac muscle development. Importantly, cell cycle was dominant pathway among downregulated genes, and decreased expression of the proteins included in cell cycle may disturb cardiomyocyte growth and differentiation during atrial septum formation. Our study provided evidences of understanding pathogenic mechanism of ASD and resource for validation of CHD genomic studies.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Comunicação Interatrial/embriologia , Septos Cardíacos/embriologia , Miócitos Cardíacos/metabolismo , Organogênese , Transcriptoma , Feminino , Comunicação Interatrial/patologia , Septos Cardíacos/patologia , Humanos , Recém-Nascido , Masculino , Miócitos Cardíacos/patologia
8.
Sci Rep ; 5: 9571, 2015 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-25826780

RESUMO

Studies have proven that IL-2 and IL-15 showed contrasting roles during CIK cells preparation. By employing microarray, we analyzed miRNA expression profiles of PBMC, CIKIL-2 and CIKIL-15. Advanced bioinformatic analyses were performed to explore the key miRNAs which may regulate cell proliferation and anti-tumor activity of CIK. We identified 261 differentially expressed miRNAs (DEMs) between PBMC and CIKIL-2, and 249 DEMs between PBMC and CIKIL-15. MiR-143-3p/miR-145-5p was miRNA cluster which may positively regulate cell proliferation. In contrast, miR-340-5p/miR-340-3p cluster may negatively regulate cell proliferation via induction apoptosis, which may cause decreased cell proliferation capacity of CIKIL-2. MiRNA-target interaction analysis indicated that 10 co-downregulated miRNAs may synergistically turn on the expression of a pool of tumor cytotoxic genes in CIK cells. The DEMs between CIKIL-2 and CIKIL-15 may contribute to enhanced tumor cytotoxic capacity of CIKIL-2. Importantly, we found that repressed miR-193a-5p may regulate the expressions of inhibitory receptor KLRD1. The results of the validation assay have shown that KLRD1 were upregulated in CIK cells. Our findings have provided new insights into mechanisms of CIK cells production and tumor cytotoxic function, and shed light on their safety for clinical trial.


Assuntos
Complexo CD3/metabolismo , Antígeno CD56/metabolismo , Células Matadoras Induzidas por Citocinas/metabolismo , Perfilação da Expressão Gênica , MicroRNAs/genética , Transcriptoma , Mapeamento Cromossômico , Análise por Conglomerados , Células Matadoras Induzidas por Citocinas/imunologia , Citotoxicidade Imunológica/genética , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Imunofenotipagem , Leucócitos Mononucleares/metabolismo , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/metabolismo , Interferência de RNA , RNA Mensageiro/genética , Reprodutibilidade dos Testes , Transdução de Sinais
9.
BMC Med Genomics ; 7: 49, 2014 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-25108500

RESUMO

BACKGROUND: Cytokine-induced killer (CIK) cells are an emerging approach of cancer treatment. Our previous study have shown that CIK cells stimulated with combination of IL-2 and IL-15 displayed improved proliferation capacity and tumor cytotoxicity. However, the mechanisms of CIK cell proliferation and acquisition of cytolytic function against tumor induced by IL-2 and IL-15 have not been well elucidated yet. METHODS: CIK(IL-2) and CIK(IL-15) were generated from peripheral blood mononuclear cells primed with IFN-γ, and stimulated with IL-2 and IL-15 in combination with OKT3 respectively. RNA-seq was performed to identify differentially expressed genes, and gene ontology and pathways based analysis were used to identify the distinct roles of IL-2 and IL-15 in CIK preparation. RESULTS: The results indicated that CIKIL-15 showed improved cell proliferation capacity compared to CIK(IL-2). However, CIK(IL-2) has exhibited greater tumor cytotoxic effect than CIKIL-15. Employing deep sequencing, we sequenced mRNA transcripts in CIK(IL-2) and CIK(IL-15). A total of 374 differentially expressed genes (DEGs) were identified including 175 up-regulated genes in CIK(IL-15) and 199 up-regulated genes in CIK(IL-2)). Among DEGs in CIK(IL-15), Wnt signaling and cell adhesion were significant GO terms and pathways which related with their functions. In CIK(IL-2, type I interferon signaling and cytokine-cytokine receptor interaction were significant GO terms and pathways. We found that the up-regulation of Wnt 4 and PDGFD may contribute to enhanced cell proliferation capacity of CIK(IL-15), while inhibitory signal from interaction between CTLA4 and CD80 may be responsible for the weak proliferation capacity of CIK(IL-2). Moreover, up-regulated expressions of CD40LG and IRF7 may make for improved tumor cytolytic function of CIK(IL-2) through type I interferon signaling. CONCLUSIONS: Through our findings, we have preliminarily elucidated the cells proliferation and acquisition of tumor cytotoxicity mechanism of CIK(IL-15) and CIK(IL-2). Better understanding of these mechanisms will help to generate novel CIK cells with greater proliferation potential and improved tumor cytolytic function.


Assuntos
Células Matadoras Induzidas por Citocinas/citologia , Células Matadoras Induzidas por Citocinas/efeitos dos fármacos , Perfilação da Expressão Gênica , Interleucina-15/farmacologia , Interleucina-2/farmacologia , Neoplasias/genética , Neoplasias/imunologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Matadoras Induzidas por Citocinas/metabolismo , Ontologia Genética , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Análise de Sequência de RNA
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