Elevated circulating level of P2X7 receptor is related to severity of coronary artery stenosis and prognosis of acute myocardial infarction

Background: Acute myocardial infarction (AMI) is a severely life-threatening cardiovascular disease. Previous research has identified an association between the P2X7 receptor (P2X7R) and the development of atherosclerosis. However, the correlation of its expression with the clinical prognosis of patients with AMI remains unclear. The present study aimed to investigate the potential role of P2X7R in Chinese patients with AMI. Methods: Seventy-nine patients with AMI and 48 controls were consecutively enrolled in this prospective observational study. Circulating P2X7R mRNA expression levels and other clinical variables were determined upon admission to the hospital. Patients were followed up for 360 days, and the end-point was considered as the occurrence of major adverse cardiovascular events (MACE). Results: Circulating P2X7R mRNA expression level in peripheral blood mononuclear cells of patients with AMI were significantly higher than those in controls and had promising diagnostic ability of AMI with an area under the curve of 0.928. Furthermore, P2X7R was demonstrated to be correlated positively with the severity of coronary artery stenosis. Additionally, this is the first study to indicate that higher P2X7R mRNA expression is associated with a higher rate of MACE within 360 days after AMI. Conclusions: The present study showed that the circulating level of P2X7R was elevated in AMI patients and was closely associated with the severity of coronary artery stenosis and prognosis of AMI

MicroRNA roles in beta-catenin pathway

β-catenin, a key factor in the Wnt signaling pathway, has essential functions in the regulation of cell growth and differentiation. Aberrant β-catenin signaling has been linked to various disease pathologies, including an important role in tumorigenesis. Here, we review the regulation of the Wnt signaling pathway as it relates to β-catenin signaling in tumorigenesis, with particular focus on the role of microRNAs. Finally, we discuss the potential of β-catenin targeted therapeutics for cancer treatment

Abnormal diastolic function underlies the different beneficial effects of cardiac resynchronization therapy on ischemic and non-ischemic cardiomyopathy

OBJECTIVES: To investigate the association between diastolic function and the different beneficial effects of cardiac resynchronization therapy in patients with heart failure due to different causes. METHODS: The 104 enrolled patients were divided into an ischemic cardiomyopathy group (n=27) and a non-ischemic cardiomyopathy group (n=77) according to the cause of heart failure. Before implantation, left ventricular diastolic function was evaluated in all patients using echocardiography. After six months of follow-up, the beneficial effects of cardiac resynchronization therapy were evaluated using a combination of clinical symptoms and echocardiography parameters. RESULTS: The ischemic cardiomyopathy group included significantly more patients with restrictive filling than the non-ischemic cardiomyopathy group. The response rate after the implantation procedure was significantly higher in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Degrees of improvement in echocardiography parameters were significantly greater in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Multivariate regression analysis showed that a restrictive filling pattern was an independent factor that influenced responses to cardiac resynchronization therapy. CONCLUSIONS: This study again confirmed that the etiology of heart failure affects the beneficial effects of cardiac resynchronization therapy and a lower degree of improvement in ventricular systolic function and remodelling was observed in ischemic cardiomyopathy patients than in non-ischemic cardiomyopathy patients. In addition, systolic heart failure patients with severe diastolic dysfunction had poor responses to cardiac resynchronization therapy. Ischemic cardiomyopathy patients exhibited more severe diastolic dysfunction than non-ischemic cardiomyopathy patients, which may be a reason for the reduced beneficial effect of cardiac resynchronization therapy

MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) can function as either oncogenes or tumor suppressor genes via regulation of cell proliferation and/or apoptosis. MiR-221 and miR-222 were discovered to induce cell growth and cell cycle progression via direct targeting of p27 and p57 in various human malignancies. However, the roles of miR-221 and miR-222 have not been reported in human gastric cancer. In this study, we examined the impact of miR-221 and miR-222 on human gastric cancer cells, and identified target genes for miR-221 and miR-222 that might mediate their biology.</p> <p>Methods</p> <p>The human gastric cancer cell line SGC7901 was transfected with AS-miR-221/222 or transduced with pMSCV-miR-221/222 to knockdown or restore expression of miR-221 and miR-222, respectively. The effects of miR-221 and miR-222 were then assessed by cell viability, cell cycle analysis, apoptosis, transwell, and clonogenic assay. Potential target genes were identified by Western blot and luciferase reporter assay.</p> <p>Results</p> <p>Upregulation of miR-221 and miR-222 induced the malignant phenotype of SGC7901 cells, whereas knockdown of miR-221 and miR-222 reversed this phenotype via induction of PTEN expression. In addition, knockdonwn of miR-221 and miR-222 inhibited cell growth and invasion and increased the radiosensitivity of SGC7901 cells. Notably, the seed sequence of miR-221 and miR-222 matched the 3'UTR of PTEN, and introducing a PTEN cDNA without the 3'UTR into SGC7901 cells abrogated the miR-221 and miR-222-induced malignant phenotype. PTEN-3'UTR luciferase reporter assay confirmed PTEN as a direct target of miR-221 and miR-222.</p> <p>Conclusion</p> <p>These results demonstrate that miR-221 and miR-222 regulate radiosensitivity, and cell growth and invasion of SGC7901 cells, possibly via direct modulation of PTEN expression. Our study suggests that inhibition of miR-221 and miR-222 might form a novel therapeutic strategy for human gastric cancer.</p

Towards bio monitoring of toxic (lead) and essential elements in whole blood from 1- to72-month old children: a cross-sectional study

Objectives: Minerals such as zinc, copper, selenium, calcium, and magnesium are essential for normal human development and functioning of the body. They have been found to play important roles in immuno-physiologic functions. The study is to evaluate the distribution and correlation of nonessential (lead) and essential elements in whole blood from 1- to 72-month old children. Methods: The cross-sectional study was performed in 1551 children. Six element concentrations, including copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe) and lead (Pb) in the blood were determined by atomic absorption spectrometry. Distributions and correlations of trace elements in different age groups were analyzed and compared. A Pearson correlation controlled for age and gender was used to assess the relationship of non essential (lead) and essential elements. Results: Levels of copper and magnesium were 18.09 \ub1 4.42 \u3bcmol/L and 1.42 \ub1 0.12 mmol/L, respectively. 6.04% of all children showed copper levels below the normal threshold, the levels of Magnesium were stable in different age groups. Though the overall mean blood zinc and iron concentrations (61.19 \ub1 11.30 \u3bcmol/L and 8.24 \ub1 0.59 mmol/L, respectively) gradually increased with age and the overall deficiency levels (24.1% and 36.0%, respectively) decreased with age, zinc and iron deficiencies were still very stable. Controlling for gender and age, significant positive correlations were found when comparing copper to zinc, calcium, magnesium, and iron((r = 0.333, 0.241, 0.417, 0.314 ,p &lt; 0.01); zinc to magnesium and iron (r = 0.440, 0.497p &lt; 0.01); and magnesium to Calcium and iron(r = 0.349, 0.645, p &lt; 0.01). The overall mean blood lead levels (41.16 \ub1 16.10) were relatively unstable among different age groups. The prevalence of lead intoxication in all children was 1.3% .Calcium levels decreased gradually with age, with an overall concentration of 1.78 \ub1 0.13 mmol/L. Conclusion: Significant negative correlations were also noted between Pb and Zn, Fe (r = -0.179, -0.124.p &lt; 0.01) .The importance of calcium deficiency and supplementation is well realized, but the severity of iron and zinc deficiency is not well recorded. The degree of lead intoxication in all the children studied was low; The established reference intervals for Cu, Zn, Ca and Mg provide an important guidance for the reasonable supplementation of essential elements during different age groups

Development of a deep learning-based tool to assist wound classification

This paper presents a deep learning-based wound classification tool that can assist medical personnel in non-wound care specialization to classify five key wound conditions, namely deep wound, infected wound, arterial wound, venous wound, and pressure wound, given color images captured using readily available cameras. The accuracy of the classification is vital for appropriate wound management. The proposed wound classification method adopts a multi-task deep learning framework that leverages the relationships among the five key wound conditions for a unified wound classification architecture. With differences in Cohen's kappa coefficients as the metrics to compare our proposed model with humans, the performance of our model was better or non-inferior to those of all human medical personnel. Our convolutional neural network-based model is the first to classify five tasks of deep, infected, arterial, venous, and pressure wounds simultaneously with good accuracy. The proposed model is compact and matches or exceeds the performance of human doctors and nurses. Medical personnel who do not specialize in wound care can potentially benefit from an app equipped with the proposed deep learning model

Exercise training with negative pressure ventilation improves exercise capacity in patients with severe restrictive lung disease: a prospective controlled study

BACKGROUND: Exercise training is of benefit for patients with restrictive lung disease. However, it tends to be intolerable for those with severe disease. We examined whether providing ventilatory assistance by using negative pressure ventilators (NPV) during exercise training is feasible for such patients and the effects of training. METHODS: 36 patients with restrictive lung disease were prospectively enrolled for a 12-week multidisciplinary rehabilitation program. During this program, half of them (n:18; 60.3 ± 11.6 years; 6 men; FVC: 32.5 ± 11.7% predicted ) received regular sessions of exercise training under NPV, whilst the 18 others (59.6 ± 12.3 years; 8 men; FVC: 37.7 ± 10.2% predicted) did not. Exercise capacity, pulmonary function, dyspnea and quality of life were measured. The primary endpoint was the between-group difference in change of 6 minute-walk distance (6MWD) after 12 weeks of rehabilitation. RESULTS: All patients in the NPV-exercise group were able to tolerate and completed the program. The between-group differences were significantly better in the NPV-exercise group in changes of 6MWD (34.1 ± 12.7 m vs. -32.5 ± 17.5 m; P = 0.011) and St George Score (−14.5 ± 3.6 vs. 11.8 ± 6.0; P < 0.01). There was an improvement in dyspnea sensation (Borg’s scale, from 1.4 ± 1.5 point to 0.8 ± 1.3 point, P = 0.049) and a small increase in FVC (from 0.85 ± 0.09 L to 0.91 ± 0.08 L, P = 0.029) in the NPV-exercise group compared to the control group. CONCLUSION: Exercise training with NPV support is feasible for patients with severe restrictive lung diseases, and improves exercise capacity and health-related quality of life

MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol

<p>Abstract</p> <p>Background</p> <p>Substantial data indicate that the oncogene microRNA 21 (miR-21) is significantly elevated in glioblastoma multiforme (GBM) and regulates multiple genes associated with cancer cell proliferation, apoptosis, and invasiveness. Thus, miR-21 can theoretically become a target to enhance the chemotherapeutic effect in cancer therapy. So far, the effect of downregulating miR-21 to enhance the chemotherapeutic effect to taxol has not been studied in human GBM.</p> <p>Methods</p> <p>Human glioblastoma U251 (PTEN-mutant) and LN229 (PTEN wild-type) cells were treated with taxol and the miR-21 inhibitor (in a poly (amidoamine) (PAMAM) dendrimer), alone or in combination. The 50% inhibitory concentration and cell viability were determined by the MTT assay. The mechanism between the miR-21 inhibitor and the anticancer drug taxol was analyzed using the Zheng-Jun Jin method. Annexin V/PI staining was performed, and apoptosis and the cell cycle were evaluated by flow cytometry analysis. Expression of miR-21 was investigated by RT-PCR, and western blotting was performed to evaluate malignancy related protein alteration.</p> <p>Results</p> <p>IC(50) values were dramatically decreased in cells treated with miR-21 inhibitor combine with taxol, to a greater extent than those treated with taxol alone. Furthermore, the miR-21 inhibitor significantly enhanced apoptosis in both U251 cells and LN229 cells, and cell invasiveness was obviously weakened. Interestingly, the above data suggested that in both the PTEN mutant and the wild-type GBM cells, miR-21 blockage increased the chemosensitivity to taxol. It is worth noting that the miR-21 inhibitor additively interacted with taxol on U251cells and synergistically on LN229 cells. Thus, the miR-21 inhibitor might interrupt the activity of EGFR pathways, independently of PTEN status. Meanwhile, the expression of STAT3 and p-STAT3 decreased to relatively low levels after miR-21 inhibitor and taxol treatment. The data strongly suggested that a regulatory loop between miR-21 and STAT3 might provide an insight into the mechanism of modulating EGFR/STAT3 signaling.</p> <p>Conclusions</p> <p>Taken together, the miR-21 inhibitor could enhance the chemo-sensitivity of human glioblastoma cells to taxol. A combination of miR-21 inhibitor and taxol could be an effective therapeutic strategy for controlling the growth of GBM by inhibiting STAT3 expression and phosphorylation.</p

MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma

<p>Abstract</p> <p>Background</p> <p>MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive.</p> <p>Results</p> <p>Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues.</p> <p>Conclusion</p> <p>To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention.</p