Validation of the V-RESOLVE (Visual Estimation for Risk prEdiction of Side Branch OccLusion in Coronary Bifurcation interVEntion) score system.

OBJECTIVES: This study sought to validate the V-RESOLVE score system. BACKGROUND: The V-RESOLVE score was developed to predict the risk of side branch (SB) occlusion after stenting in the main vessel (MV) of coronary bifurcation lesions based on visual estimation of the angiographic data, but it needed to be validated. METHODS: From January to June 2013, 1,286 patients with 1,820 bifurcation lesions undergoing elective intervention with provisional strategy were included. Angiographic data before MV stenting were reviewed, and the V-RESOLVE score was calculated. SB occlusion was defined as any decrease in thrombolysis in myocardial infarction (TIMI) flow grade or the absence of flow in the SB after MV stenting. The statistical performance of the prediction model was assessed by its discrimination, calibration, and clinical usefulness. RESULTS: SB occlusion occurred in 222 (12.20%) of 1,820 bifurcation lesions. The discrimination of the V-RESOLVE score for the validation cohort was good [C-statistic: 0.80, 95% confidence interval (CI) 0.77-0.84]. Regarding calibration performance, the calibration-in-the-large was -0.03 (95% CI: -0.181 to 0.12), while the combined predictive effect was slightly enlarged (calibration slope: 1.25, 95% CI: 1.081-1.41) and, mainly attributed to the stronger predictive effect of the diameter stenosis of the SB before MV stenting. Stratified by the V-RESOLVE score, the SB occlusion rate was significantly higher in the high-risk group (26.18%) than in the non-high-risk group (3.48%). CONCLUSIONS: The V-RESOLVE score system is a useful tool to help risk prediction for SB occlusion and decision-making in bifurcation intervention.

Risk stratification of periprocedural myocardial infarction after percutaneous coronary intervention: Analysis based on the SCAI definition.

OBJECTIVES: To investigate the predictors of and generate a risk prediction method for periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) using the new PMI definition proposed by the Society for Cardiovascular Angiography and Interventions (SCAI). BACKGROUND: The SCAI-defined PMI was found to be associated with worse prognosis than the PMI diagnosed by other definitions. However, few large-sample studies have attempted to predict the risk of SCAI-defined PMI. METHODS: A total of 3,371 patients (3,516 selective PCIs) were included in this single-center retrospective analysis. The diagnostic criteria for PMI were set according to the SCAI definition. All clinical characteristics, coronary angiography findings and PCI procedural factors were collected. Multivariate logistic regression analysis was performed to identify independent predictors of PMI. To evaluate the risk of PMI, a multivariable risk score (PMI score) was constructed with incremental weights attributed to each component variable according to their estimated coefficients. RESULTS: PMI occurred in 108 (3.1%) of all patients. Age, multivessel treatment, at least one bifurcation treatment and total treated lesion length were independent predictors of SCAI-defined PMI. PMI scores ranged from 0 to 20. The C-statistic of PMI score was 0.71 (95% confidence interval: 0.66-0.76). PMI rates increased significantly from 1.96% in the non-high-risk group (PMI score < 10) to 6.26% in the high-risk group (PMI score ≥ 10) (P < 0.001). CONCLUSIONS: Age, multivessel treatment, at least one bifurcation treatment, and total treated lesion length are predictive of PMI. The PMI score could help identify patients at high risk of PMI after PCI. © 2017 Wiley Periodicals, Inc.

Analysis of the essential oil from Gaillardia pulchella Foug. and its antioxidant activity.

The essential oil from Gaillardia pulchella Foug. flowers was obtained by hydrodistillation and its chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). Twenty-eight compounds representing 92.63% of the essential oil were identified, of which the most prominent were n-Hexadecanoic acid (26.90%), Phytol (7.58%) and Cyclopropaneoctanoic acid, 2-[[2-[(2-ethylcyclopropyl) methyl] cyclopropyl] methyl]-, methyl ester (6.73%). Meanwhile, antioxidant activity of the essential oil was tested. The essential oil showed certain antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) with an EC50 of 70.95 µg/ml. This is the first report on the essential oil of this particular species. Its bioactivities warrant further studies.

PU.1 can regulate the ZNF300 promoter in APL-derived promyelocytes HL-60.

ZNF300, which plays the role in human embryonic development and some diseases, is a typical KRAB/C2H2 zinc finger gene expressed only in higher mammalians. Our data showed that expression of ZNF300 changed significantly in various leukemia blasts in the bone marrow aspirates of newly diagnosed leukemia patients. To investigate the potential relationship between expression of ZNF300 and the progression of leukemia development and hematopoietic differentiation, we cloned and characterized the putative human ZNF300 gene promoter and identified its transcription start sites (TSSs). Deletion and mutagenesis analysis demonstrated that a myeloid-specific transcription factor PU.1 binding site was responsible for myeloid-specific regulation of ZNF300 promoter activity. Furthermore, electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that PU.1 bound to the PU.1 binding site within ZNF300 promoter region in vitro and in vivo. Overexpression of PU.1 elevated ZNF300 promoter activity, whereas silencing of PU.1 expression significantly reduced the activity in myeloid-derived HL-60 cell but not in T-cell Jurkat. In vitro induced HL-60 cells into CD11b expressing cells by DMSO demonstrated that ZNF300 was upregulated along with upregulation of PU.1 expression. These results demonstrated that ZNF300 was activated by PU.1 and suggested that the regulation may be involved in the progression of leukemia development and hematopoietic differentiation.

Increased peripheral circulating inflammatory cells and plasma inflammatory markers in patients with variant angina.

BACKGROUND: Emerging data suggest that inflammation may play an important role in the pathogenesis of coronary artery disease. However, the relation of inflammatory status to coronary vasospasm has been less investigated in patients with variant angina (VA). PURPOSE: The aim of this study, therefore, was to determine peripheral circulating white blood cells as well as monocyte cells and plasma C-reactive protein (CRP) and interleukin-6 (IL-6) levels in patients with VA, and to compare patients with VA, stable coronary artery disease, and controls with angiographically normal coronary arteries. METHOD: Thirty-three consecutive patients with documented VA, 26 with stable coronary artery disease, and 22 normal controls (with angiographically normal coronary arteries) were involved in this study. The peripheral blood was taken, and white blood cells and monocyte cells were counted. The plasma concentrations of CRP and IL-6 were also evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The data showed that white blood cell counts and monocyte cell counts were significantly higher in patients of the VA group than in the other two groups (white blood cell counts: 7340+/-1893/mm vs. 6187+/-1748/mm vs. 5244+/-1532/mm, P<0.05, respectively; monocyte cell counts: 510+/-213/mm vs. 425+/-209/mm vs. 383+/-192/mm, P<0.05, respectively). Similarly, levels of plasma CRP and IL-6 were also significantly higher in patients of the VA group than in patients with stable coronary artery disease (CRP: 0.42+/-0.21 mg/l vs. 0.27+/-0.14 mg/l; IL-6: 10.4+/-1.0 pg/dl vs. 6.2+/-0.7 pg/dl, P<0.01, respectively), and patients with normal controls (CRP: 0.42+/-0.21 mg/l vs. 0.17+/-0.10 mg/l; IL-6: 10.4+/-1.0 pd/dl vs. 3.0+/-0.7 pg/dl, P<0.01, respectively). The multivariate analysis showed that CRP was the independent variable most strongly associated with VA. CONCLUSION: Taken together, these findings suggested that more chronic, severe inflammation might be involved in the pathogenesis of VA, manifested by increased counts of circulating inflammatory cells and elevated plasma levels of CRP and IL-6.

Human T-cell leukemia virus type 1 oncoprotein tax represses ZNF268 expression through the cAMP-responsive element-binding protein/activating transcription factor pathway.

Expression of the human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax is correlated with cellular transformation, contributing to the development of adult T-cell leukemia. In this study, we investigated the role of Tax in the regulation of the ZNF268 gene, which plays a role in the differentiation of blood cells and the pathogenesis of leukemia. We demonstrated that ZNF268 mRNA was repressed in HTLV-1-infected cells. We also showed that stable and transient expression of HTLV-1 Tax led to repression of ZNF268. In addition, by using reporter constructs that bear the human ZNF268 promoter and its mutants, we showed that Tax repressed ZNF268 promoter in a process dependent on a functional cAMP-responsive element. By using Tax, cAMP-responsive element-binding protein (CREB)-1, CREB-2, and their mutants, we further showed that Tax repressed ZNF268 through the CREB/activating transcription factor pathway. Electrophoretic mobility shift assays and chromatin immunoprecipitation demonstrated the formation of the complex of Tax.CREB-1 directly at the cAMP-responsive element both in vitro and in vivo. These findings suggest a role for ZNF268 in aberrant T-cell proliferation observed in HTLV-1-associated diseases.

Elevated circulating inflammatory markers in female patients with cardiac syndrome X.

BACKGROUND: The pathophysiological mechanism in cardiac syndrome X has been suggested as impairment in normal endothelial function of the coronary microvasculature, resulting in inadequate flow reserve. However, despite the extensive studies, the precise mechanisms in cardiac syndrome X remain unclear. PURPOSE: The present study was, therefore, to investigate whether inflammatory cells and markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) might be involved in the pathogenesis of cardiac syndrome X. METHODS: Thirty-six female patients with cardiac syndrome X and 30 sex-matched normal controls were prospectively enrolled in this study. Blood samples were drawn for measuring white blood and monocyte cells, inflammatory markers such as CRP and IL-6, and data were compared between patients with cardiac syndrome X and normal controls. RESULTS: The data showed that increased numbers of white blood and monocyte cells were found in patients with cardiac syndrome X compared with normal controls (white blood cells: 7072+/-1146/mm(3) vs. 6138+/-1079/mm(3); monocyte cells: 612+/-186/mm(3) vs. 539+/-190/mm(3)p<0.05, respectively). Moreover, patients with cardiac syndrome X were detected to have significantly higher plasma CRP and IL-6 levels in comparison with patients with normal controls (CRP: 0.48+/-0.26 mg/L vs. 0.22+/-0.15 mg/L; IL-6: 13.4+/-1.2 pg/dl vs. 6.2+/-0.6 pg/dl, p<0.01, respectively). The multivariate analysis showed that CRP was the independent variable most strongly associated with cardiac syndrome X. CONCLUSIONS: Our data suggested that low-grade, chronic inflammation might contribute to the development of cardiac syndrome X manifested by increased plasma levels of inflammatory cells and inflammatory markers.

The role of inflammation in coronary artery calcification.

Vascular calcification is an age-dependent, common finding in human coronary arteries and begins as early as the second decade of life, just after fatty streak formation. Previous studies have showed that the severity of coronary calcification is closely related to atherosclerotic plaque burden and cardiac event rate. In the past few decades, coronary calcification has been considered passive and degenerative. With recent clinical and basic research, however, there is increasing recognition that coronary calcification is an active, regulated process. Current diagnostic methods for coronary artery calcification (CAC) are usually traditional coronary angiography, intravascular ultrasound (IVUS), electron beam computed tomography (EBCT) and multi-slice computed tomography (MSCT) while treatment for patients with calcified coronary arteries is troublesome. Several lines of evidence suggest that inflammation plays a major role in the development of atherosclerosis as well as its clinical manifestations. Recent study showed that inflammatory process might be also involved in coronary calcification. Accordingly, measurements of inflammatory markers such as C-reactive protein (CRP) may in part reflect indices of atherosclerosis, such as coronary calcification, and are likely to provide distinct information regarding cardiovascular risk. In this article, we review the current evidence of relationship between coronary calcification and inflammation for purpose of drawing the more attention on the inflammatory mechanism of coronary calcification, which may change our research as well as therapeutic strategies for coronary calcification in the future.

Transcription of human zinc finger ZNF268 gene requires an intragenic promoter element.

Human ZNF268 gene is a typical Krüppel-associated box/C2H2 zinc finger gene whose homolog has been found only in higher mammals and not in lower mammals such as mouse. Its expression profiles have suggested that it plays a role in the differentiation of blood cells during early human embryonic development and the pathogenesis of leukemia. To gain additional insight into the molecular mechanisms controlling the expression of the ZNF268 gene and to provide the necessary tools for further genetic studies of leukemia, we have mapped the 5'-end of the human ZNF268 mRNA by reverse transcription-PCR and primer extension assays. We then cloned the 5'-flanking genomic DNA containing the putative ZNF268 gene promoter and analyzed its function in several different human and mouse tissue culture cell lines. Interestingly, our studies show that the ZNF268 gene lacks a typical eukaryotic promoter that is present upstream of the transcription start site and directs a basal level of transcription. Instead, the functional promoter requires an essential element that is located within the first exon of the gene. Deletion and mutational analysis reveals the requirement for a cAMP response-element-binding protein (CREB)-binding site within this element for promoter function. Gel mobility shift and chromatin immunoprecipitation assays confirm that CREB-2 binds to the site in vitro and in vivo. Furthermore, overexpression of CREB-2 enhances the promoter activity. These results demonstrate that the human ZNF268 gene promoter is atypical and requires an intragenic element located within the first exon that mediates the effect of CREB for its activity.