Effects of exercise on heart failure with preserved ejection fraction: An updated review of literature

Heart failure with preserved ejection fraction (HFpEF) represents the most common HF phenotype of patients aged > 65 years, with an incidence and a prevalence that are constantly growing. The HFpEF cardinal symptom is exercise intolerance (EI), defined as the impaired ability to perform physical activity and to reach the predicted age-related level of exercise duration in the absence of symptoms—such as fatigue or dyspnea—and is associated with a poor quality of life, a higher number of hospitalizations, and poor outcomes. The evidence of the protective effect between exercise and adverse cardiovascular outcomes is numerous and long-established. Regular exercise is known to reduce cardiovascular events and overall mortality both in apparently healthy individuals and in patients with established cardiovascular disease, representing a cornerstone in the prevention and treatment of many cardio-metabolic conditions. Several studies have investigated the role of exercise in HFpEF patients. The present review aims to dwell upon the effects of exercise on HFpEF. For this purpose, the relevant data from a literature search (PubMed, EMBASE, and Medline) were reviewed. The analysis of these studies underlines the fact that exercise training programs improve the cardiorespiratory performance of HFpEF patients in terms of the increase in peak oxygen uptake, the 6 min walk test distance, and the ventilatory threshold; on the other hand, diastolic or systolic functions are generally unchanged or only partially modified by exercise, suggesting that multiple mechanisms contribute to the improvement of exercise tolerance in HFpEF patients. In conclusion, considering that exercise training programs are able to improve the cardiorespiratory performance of HFpEF patients, the prescription of exercise training programs should be encouraged in stable HFpEF patients, and further research is needed to better elucidate the pathophysiological mechanisms underpinning the beneficial effects described

Modulation of HJURP (Holliday Junction-Recognizing Protein) Levels Is Correlated with Glioblastoma Cells Survival

<div><p>Background</p><p>Diffuse astrocytomas are the most common type of primary brain cancer in adults. They present a wide variation in differentiation and aggressiveness, being classified into three grades: low-grade diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III) and glioblastoma multiforme (grade IV), the most frequent and the major lethal type. Recent studies have highlighted the molecular heterogeneity of astrocytomas and demonstrated that large-scale analysis of gene expression could help in their classification and treatment. In this context, we previously demonstrated that HJURP, a novel protein involved in the repair of DNA double-strand breaks, is highly overexpressed in glioblastoma.</p><p>Methodology/Principal Findings</p><p>Here we show that HJURP is remarkably overexpressed in a cohort composed of 40 patients with different grade astrocytomas. We also observed that tumors presenting the higher expression levels of HJURP are associated with poor survival prognosis, indicating HJURP overexpression as an independent prognostic factor of death risk for astrocytoma patients. More importantly, we found that HJURP knockdown strongly affects the maintenance of glioblastoma cells in a selective manner. Glioblastoma cells showed remarkable cell cycle arrest and premature senescence that culminated in elevated levels of cell death, differently from non-tumoral cells that were minimally affected.</p><p>Conclusions</p><p>These data suggest that HJURP has an important role in the maintenance of extremely proliferative cells of high-grade gliomas and point to HJURP as a potential therapeutic target for the development of novel treatments for glioma patients.</p></div

HJURP expression ranges are correlated with patient survival.

<p>P-value = 0.002, long-rank (Mantel-Cox) test.</p

U87MG cells enter in premature senescence after HJURP knockdown.

<p>(A) Images of U87MG cells at the indicated times after transfection with siControl or siHJURP double-stranded RNAs were captured under phase-contrast microscopy (Leica MC OS). (B) U87MG cells subjected to the indicated treatments were processed for the β-galactosidase assay at the fifth day after transfection. Graphic shows the percentage of senescent cells in each condition. Measurements were performed in three independent experiments. ***P<0.0001, T-test.</p

Cell cycle and viability analysis of non-tumoral and glioma cells after HJURP silencing.

<p>RO, T98G, and U87MG cells, were transfected with control double-stranded siRNA or with siRNA directed against HJURP mRNA. Cells submitted to the different treatments were fixed, labeled with propidium iodide and their DNA content was measured by flow cytometry analysis. (A, B and C) Percentage of cells in each cell cycle phase at different times after transfection. N = 3, *P<0.05, T test. RO and T98G cells subjected to the different treatments were stained with propidium iodide for viability analysis. (D) Percentages of cell death in 5 consecutive days after transfection are shown. n = 3, P<0.001 (T-test) for comparisons between T98G cells treated with siControl <i>versus</i> siHJURP at the third, fourth and fifth days.</p

Multivariate analysis of prognostic factors in patients with glioma using Cox regression.

<p>Multivariate analysis of prognostic factors in patients with glioma using Cox regression.</p

Levels of HJURP mRNA are increased in different grade astrocytomas and correlated with survival prognosis.

<p>(A) Expression levels of HJURP mRNA in samples of normal white matter (WM, n = 7), diffuse atrocytoma (AST II, n = 5), anaplastic astrocytoma (AST III, n = 5) and glioblastoma multiforme (GBM, n = 30) were evaluated by quantitative RT-PCR. Boxes represent lower and upper quartiles of HJURP relative expression ranges, with medians indicated. Whiskers represent the 10^th and 90^th percentiles. **P-value = 0.0025 and ***P-value <0.0001 in comparison with normal white matter, Mann-Whitney test. (B) Kaplan Meier survival curves for glioma patients according to the HJURP expression levels in the tumors. Patients were divided in two groups: i) HJURP relative quantities below 39.7 (threshold value determined by ROC curve) (solid line, n = 9), and ii) HJURP relative quantities above 39.7 (dashed line, n = 31). The P-value shown was obtained from a long-rank test. Graphs were plotted with GraphPad Prism 4.0 software.</p

Identification of unannotated exons of low abundance transcripts in and cloning of a new serine protease gene upregulated upon injury-0

<p><b>Copyright information:</b></p><p>Taken from "Identification of unannotated exons of low abundance transcripts in and cloning of a new serine protease gene upregulated upon injury"</p><p>http://www.biomedcentral.com/1471-2164/8/249</p><p>BMC Genomics 2007;8():249-249.</p><p>Published online 24 Jul 2007</p><p>PMCID:PMC1949825.</p><p></p>ch [16]

Identification of unannotated exons of low abundance transcripts in and cloning of a new serine protease gene upregulated upon injury-4

<p><b>Copyright information:</b></p><p>Taken from "Identification of unannotated exons of low abundance transcripts in and cloning of a new serine protease gene upregulated upon injury"</p><p>http://www.biomedcentral.com/1471-2164/8/249</p><p>BMC Genomics 2007;8():249-249.</p><p>Published online 24 Jul 2007</p><p>PMCID:PMC1949825.</p><p></p>ith a needle dipped into 10cells/ml cultures of either Gram() or Gram() bacteria or fungi (). Note that asceptic pricking by itself triggers the induction of the SP212, albeit at a lower level

Identification of unannotated exons of low abundance transcripts in and cloning of a new serine protease gene upregulated upon injury-1

<p><b>Copyright information:</b></p><p>Taken from "Identification of unannotated exons of low abundance transcripts in and cloning of a new serine protease gene upregulated upon injury"</p><p>http://www.biomedcentral.com/1471-2164/8/249</p><p>BMC Genomics 2007;8():249-249.</p><p>Published online 24 Jul 2007</p><p>PMCID:PMC1949825.</p><p></p>re hybridized to the probes indicated at the bottom of each blot. The estimated size (kb) of each transcript is indicated on the left