Atherosclerosis is the major cause of stroke and heart disease. However, the course and pathogenesis of atherosclerosis remains unknown. The proliferation and migration of endothelial cell play important roles in the inition and pathological progression of atherosclerosis. In this study, we demonstrated that long noncoding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) expression level was higher in coronary artery disease (CAD) tissues than in normal arterial tissues. The expression level of HOTTIP was upregulated in the proliferating endothelial cells induced by TNF-α or PDGF-BB. Ectopic expression of HOTTIP promoted endothelial cell proliferation and also increased the expression of proliferating makers cyclin D1 and PCNA. Moreover, elevated expression of HOTTIP promoted endothelial cell migration. Downregulation expression of HOTTIP suppressed endothelial cell proliferation and migration. Furthermore, we determined that overexpression of HOTTIP induced β-catenin expression and enhanced the downstream protein c-Myc expression in the endothelial cell. Ectopic expression of HOTTIP increased endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway. These results suggested that HOTTIP might manipulate the endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway.

Vascular neointimal hyperplasia and remodeling arising from local inflammation are characteristic pathogeneses of proliferative cardiovascular diseases, such as atherosclerosis and post angioplasty restenosis. The molecular mechanisms behind these pathological processes have not been fully determined. The adipokine chemerin is associated with obesity, metabolism, and control of inflammation. Recently, chemerin has gained increased attention as it was found to play a critical role in the development of cardiovascular diseases. In this study, we investigated the effects of chemerin on the regulation of vascular smooth muscle cells and carotid neointimal formation after angioplasty. We found that circulating chemerin levels increased after carotid balloon injury, and that knockdown of chemerin significantly inhibited the proliferative aspects of vascular smooth muscle cells induced by platelet-derived growth factor-BB and pro-inflammatory chemokines in vitro as well as prohibited carotid neointimal hyperplasia and pro-inflammatory chemokines in vivo after angioplasty. Additionally, inhibition of chemerin down-regulated the expression of several proteins, including phosphorylated p38 mitogen-activated protein kinase, phosphorylated extracellular signal regulated kinase 1/2, nuclear factor-kappa B p65, and proliferation cell nuclear antigen. The novel finding of this study is that chemerin stimulated vascular smooth muscle cells proliferation and carotid intimal hyperplasia through activation of the mitogen-activated protein kinase signaling pathway, which may lead to vascular inflammation and remodeling, and is relevant to proliferative cardiovascular diseases.

BackgroundThe disorder of lipid metabolism and genetic predisposition are major risk factors for coronary artery disease (CAD). Variants in the apolipoprotein A1 (APOA1) gene play an important role in the regulation of lipids. The objective of the present study was to investigate the effect of two polymorphisms (-75 G/A and +83 C/T) of APOA1 on lipid profiles and the risk of CAD.MethodsA total number of 300 subjects with CAD and 300 age and sex matched healthy controls were enrolled for the study. Genotyping of the APOA1 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsThe frequencies of APOA1 -75 AA genotype [odds ratio (OR) =0.50, 95 % confidence interval (CI) = 0.28, 0.88; P = 0.02] and APOA1 -75 A allele (OR =0.76, 95 % CI = 0.59, 0.98; P = 0.04) were significantly lower in CAD than in controls. The APOA1 -75 A allele was significantly associated with increasing serum concentrations of ApoA1 and high-density lipoprotein cholesterol (HDL-C) (P < 0.001).ConclusionsThe individuals with the APOA1 -75 A allele were likely to have a lower risk of CAD as a result of its effect on higher serum concentrations of ApoA1 and HDL-C.

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Published genetic association studies have produced controversial results regarding the association of SELE gene polymorphisms (A516C and G98T) and CAD susceptibility. We therefore chose to perform a meta-analysis to determine the association.Twenty-seven eligible articles were identified through electronic databases, providing 5170 CAD cases and 4996 controls. Fixed-effects or random-effects summary ORs were calculated to estimate the risk of CAD in relation to A516C and G98T. Forest plots and funnel plots were constructed by Stata software 12.0.A strong association was observed between A516C and susceptibility of CAD among 4757 cases and 4272 controls. The summary OR was greatest in individuals carrying the CC genotype (OR = 1.91, 95% CI, 1.12–3.25). A significantly increased risk was indicated in both Caucasians and Asians. The analyses by disease type showed a significant increase in the risk of AP and MI. We also noted a strong association in population-based studies. In the analyses of G98T, data were available for 1422 cases and 1625 controls. We saw a markedly increased risk of CAD associated with G98T. The highest risk was indicated in individuals with the TT genotype (OR = 2.82, 95% CI, 1.15–6.89). A similar trend was seen in Asians and population-based studies.These findings provide consistent evidence that A516C and G98T polymorphisms of the SELE gene may be associated with increased susceptibility of CAD.

Background: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play vital regulatory roles in pancreatic cancer (PC) initiation and progression. We aimed to explore the biological functions and underlying mechanisms of miR-505-3p (miR-505) in PC.Methods: We first screened miRNA expression profiles using microarray in PC tissues and normal tissues, and then studied the function and underlying mechanism of miR-505. Moreover, we evaluated the regulatory effect of lncRNA LINC01448 on miR-505.Results: We demonstrated miR-505 that was significantly downregulated in PC tissues. We further revealed that miR-505 significantly inhibited cell proliferation, invasion, sphere formation, glucose consumption, and lactate production by targeting HK2. In addition, overexpression of miR-505 led to tumor growth inhibition in vivo, demonstrating that it acts as a tumor suppressor in PC. LINC01448 was identified as an oncogenic lncRNA that could reduce miR-505 expression. Subsequent studies confirmed that LINC01448 enhanced cell proliferation, invasion, sphere formation, glucose consumption, and lactate production by regulating the miR-505/HK2 pathway.Conclusions: These findings demonstrated that miR-505, suppressed by LINC01448, could function as a key tumor suppressor by targeting HK2 in PC, elucidating an important role of the LINC01448/miR-505/HK2 pathway in regulating PC glycolysis and progression.

The prognostic value of the sequential organ failure assessment (SOFA) score for critically ill elderly patients with acute infective endocarditis (IE) remains unknown. From January 2015 to December 2019, 111 elderly (≥65 years) patients with acute IE were consecutively included and divided into a low SOFA (<6) group (n = 71) and a high SOFA (≥6) group (n = 40). Endpoints included in-hospital and long-term (12-36 month) mortality. A high SOFA score was related to higher incidence of in-hospital mortality (30.0%) with an area under the curve (AUC) of 0.796. In multivariate analysis, age [odds ratio (OR) = 2.21, 95% confidence intervals (CI), 1.16-6.79, p = 0.040], SOFA ≥6 (OR = 6.38, 95% CI, 1.80-16.89, p = 0.004) and surgical treatment (OR = 0.21, 95% CI, 0.05-0.80, p = 0.021) were predictive of in-hospital mortality. A Cox proportional-hazards model identified age [Hazard ratios (HR)= 2.85, 95% CI, 1.11-7.37, p = 0.031], diabetes mellitus (HR = 3.99, 95% CI, 1.35-11.80, p = 0.013), SOFA ≥6 (OR = 3.38, 95% CI, 1.26-9.08, p = 0.001) and surgical treatment (HR = 0.24, 95% CI, 0.08-0.68, p = 0.021) as predictors of long-term mortality. A high SOFA score predicts a poor outcome including in-hospital and long-term mortality in critically ill elderly patients with acute IE.

Pancreatic cancer is a highly lethal gastrointestinal malignancy. Most patients are already in the middle to advanced stages of pancreatic cancer at the time of diagnosis and cannot be treated completely. As a single-atom planar two-dimensional crystal, graphene’s unusual electronic structure, specific electronic properties and excellent electron transport capacity make it uniquely advantageous in the field of electrochemical sensing. In this mini-review, we summarize the potential application of graphene in pancreatic cancer detection. K-Ras gene, CEA and MicroRNA are important in the early diagnosis of pancreatic cancer.