Bistability and Oscillations in Gene Regulation Mediated by Small Noncoding RNAs

The interplay of small noncoding RNAs (sRNAs), mRNAs, and proteins has been shown to play crucial roles in almost all cellular processes. As key post-transcriptional regulators of gene expression, the mechanisms and roles of sRNAs in various cellular processes still need to be fully understood. When participating in cellular processes, sRNAs mainly mediate mRNA degradation or translational repression. Here, we show how the dynamics of two minimal architectures is drastically affected by these two mechanisms. A comparison is also given to reveal the implication of the fundamental differences. This study may help us to analyze complex networks assembled by simple modules more easily. A better knowledge of the sRNA-mediated motifs is also of interest for bio-engineering and artificial control

Circulating Endothelial Progenitor Cells and Clinical Outcome in Patients with Aortic Stenosis.

Aortic stenosis (AS) is the most common valvular disease. Endothelial progenitor cells (EPCs) have a role in the repair of endothelial surfaces after injury. Reduced numbers of EPCs are associated with endothelial dysfunction and adverse clinical events, suggesting that endothelial injury in the absence of sufficient repair by circulating EPCs promotes the progression of vascular and possibly valvular disorders. The aim of this study was to assess EPC number in patients with AS and to study the predictive value of their circulating levels on prognosis.The number of EPCs was determined by flow cytometry in 241 patients with AS and a control group of 73 pts. Thirty-eight, 52 and 151 patients had mild, moderate and severe AS, respectively. We evaluated the association between baseline levels of EPCs and death from cardiovascular causes during follow up.EPC level was significantly higher in patients with AS compared to the control group (p = 0.017). Two hundred and three patients with moderate and severe AS were followed for a median of 20 months. One hundred and twenty patients underwent an intervention. Thirty four patients died during follow up, 20 patients died due to cardiac causes. Advanced age, the presence of coronary artery disease, AS severity index (combination of high NYHA class, smaller aortic valve area and elevated pulmonary artery pressure) and a low EPC number were predictors of cardiac death in the univariate analysis. Multivariate logistic regression model identified low EPCs number and AS severity index as associated with cardiac death during follow up (p = 0.026 and p = 0.037, respectively).EPC number is increased in patients with AS. However, in patients with moderate or severe AS a relatively low number of EPCs is associated with cardiac death at follow up. These results may help to identify AS patients at increased cardiovascular risk

Correlation between anti EPC abs, laboratory results and biomarkers.

<p>Correlation between anti EPC abs, laboratory results and biomarkers.</p

Association of anti-EPC abs with circulating EPC and with VCAM-1 expression on HUVEC and EPC.

<p>Serum anti-EPC levels were correlated with circulating CD34+KDR+EPC (A) and with surface expression of the adhesion molecule VCAM-1 on HUVEC (B) and late outgrowth EPC (C).</p

Baseline characteristics of the study population.

<p>DM-Diabetes mellitus, HTN-Hypertension, HG-Hemoglobin, WBC-White blood cells, TG-triglyceride, HDL-high density lipoprotein, LDL-low density lipoprotein.</p

Analysis of late outgrowth EPC and binding characteristics of circulating anti-EPC antibodies.

<p>Late outgrowth EPC were obtained from several healthy individuals as described in methods. FACS was used test for surface marker expression (Left panel). To determine if antibodies to EPC are identical to AECA we performed competitive inhibition studies where anti-EPC or AECA were preincubated with EPC or AECA at different ratios and their binding to sold phase bound EPC or HUVEC tested by ELISA as described in methods (Right panel).</p

Association between anti-EPC levels and risk factors for atherosclerotic vascular disease.

<p>Levels of anti-EPC abs were determined by cyto ELISA as described in methods. The levels were correlated with the presence of individual risk factors (Age, gender, presence of hypertension and diabetes mellitus) and cumulative Framingham score.</p

Circulating Regulatory B-Lymphocytes in Patients with Acute Myocardial Infarction: A Pilot Study

Background: Inflammation plays on important role in plaque instability and acute coronary syndromes. The anti-inflammatory effects of B-regulatory lymphocytes (B-regs) in atherosclerosis was tested mainly in animal models with inconclusive results. Herein, we studied for the first time, levels of circulating B-regs in patients with acute myocardial infarction (MI). Methods: We examined circulating levels of B-regs by flow cytometry in 29 patients with recent ST-segment elevation MI and 18 patients with stable angina pectoris (SAP) and coronary artery disease. We re-assessed B-reg levels on average 4 months later. Results: The mean level of CD20+ cells was similar in patients with MI and patients with SAP (p = 0.60). The levels of CD24hiCD38hi cells among CD20+ cells were 5.7 ± 4% and 11.6 ± 6% in patients with MI and SAP, respectively, (p hiCD38hi B-regs remained related to acute MI after correcting for age, gender, and risk factors. Circulating levels of CD24hiCD38hi B-regs in patients with MI did not change significantly at follow-up in a small patient groups (p = 0.408). Conclusions: Circulating B-regs are reduced in patients with MI compared to patients with SAP. This finding may shed further light on the inflammatory pathophysiologic factors related to plaque rupture

Urea level is an independent predictor of mortality in patients with severe aortic valve stenosis.

INTRODUCTION:Severe aortic stenosis (AS) is the most common valvular heart disease in the western world. Various factors are related to severe AS prognosis, including chronic kidney disease. The aim of this study was to evaluate the prognostic value of urea level in patients with severe AS. METHODS:We prospectively enrolled 142 patients (79.1±9.4 years, 88 women) with severe AS (mean valve area 0.67± 0.17 cm2). Clinical assessment, blood tests and echocardiography were performed at enrollment and follow up. The patient population was divided into low and high urea level groups, according to the median urea level at enrollment (72 patients, mean urea 35.5±6.2 mg/dL and 70 patients, mean urea 61.1±17.8 mg/dL, respectively). Hundred and twelve patients (79%) underwent aortic valve intervention. The primary endpoint was all-cause and cardiovascular mortality. OUTCOMES:During follow-up of 37±19.5 months, 56 (37.1%) patients died, 39 due to cardiovascular causes. In univariate analysis, age, urea level, creatinine, New York Heart Association (NYHA) class and aortic valve intervention were associated with all-cause mortality. However, in multivariate analysis only aortic valve intervention and blood urea were independent predictors of all-cause mortality (HR 0.494; 95% CI 0.226-0.918, P = 0.026 and HR 1.015; 95% CI 1.003-1.029, P = 0.046 respectively). Urea level, NYHA class and age were also significant predictors of cardiovascular mortality. Whereas, in multivariate analysis, only urea level predicted cardiovascular mortality in these patients (HR 1.017; CI 1.003-1.031 P = 0.019). CONCLUSIONS:Blood urea, a generally readily available and routinely determined marker of renal function, is an independent prognostic factor in patients with severe AS

FACS analysis of circulating EPCs in patients with aortic valve stenosis (AS) and controls.

<p><b>A.</b> Isotope control; B. A representative example of a FACS analysis for the quantification of CD34+/KDR+ cells in patient with AS and patient with no AS is shown. R1, viable cells; R2, cells positive for CD34 and KDR.</p