Mechanism of hypoxia-induced exosome circ_0051799 regulating the progression of lung adenocarcinoma.

This study attempted to investigate the effect of circ_0051799 on the immune microenvironment of lung adenocarcinoma (LUAD) and the relationship between circ_0051799 and exosomes. The number and morphology of exosomes were verified by nanoparticle tracking, transmission electron microscopy and western blotting. CCK8, EdU, Transwell and flow cytometry were used to verify the regulatory role of exosomes and circ_0051799 on tumor progression. Dual luciferase reporting and RNA immunoprecipitation were used to verify the targeted regulatory relationship between circ_0051799, miR-214-3p and IGF2BP3. WB was used to verify the role of the JAK/STAT pathway in circ_0051799 regulation. Ectopic tumor grafts and in situ models were used to validate in vivo their role in regulating LUAD progression. Hypoxic environment could alter but does not alter its shape. Exosomes can participate in the regulation of macrophage polarization by circ_0051799. In vitro and in vivo assays had shown that circ_0051799 could affect the proliferation and metastasis of LUAD through targeting miR-214-3p mediated IGF2BP3 regulated JAK/STAT pathway. This study found that hypoxia can affect LUAD process by promoting the regulation of macrophage polarization by exosome circ_0051799.

Validity of SOFA score as a prognostic tool for critically ill elderly patients with acute infective endocarditis.

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.

Long noncoding RNA HOTTIP promotes endothelial cell proliferation and migration via activation of the Wnt/ß-catenin pathway.

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 ß-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/ß-catenin pathway. These results suggested that HOTTIP might manipulate the endothelial cell proliferation and migration via activation of the Wnt/ß-catenin pathway.

Downregulation of microRNA-128-3p protects human esophageal squamous Het-1A cells from hydrochloric acid-induced cell injury by targeting E2F3.

This study aimed to investigate the role of microRNA-128-3p in regulating hydrochloric acid (HCl)-induced cell injury in human esophageal squamous Het-1A cells. Het-1A cells were treated with HCl (pH 4.0) to induce esophageal injury like this caused by reflux. Whether HCl induced cell injury was then assessed by detecting cell proliferation and apoptosis. The expression of miR-128-3p in HCl-treated Het-1A cells was investigated, followed by investigating the effects of miR-128-3p overexpression and suppression on HCl-induced Het-1A cell injury. In addition, the target of miR-128-3p was identified. Besides, the association between miR-128-3p and ERK and PI3K/AKT pathways was further explored. HCl inhibited the proliferation and increased apoptosis of Het-1A cells. miR-128-3p was upregulated in Het-1A cells after HCl treatment. Inhibition of miR-128-3p alleviated HCl-induced Het-1A cell injury, whereas miR-128-3p overexpression further aggravated this injury. Moreover, E2F3 was confirmed as a target of miR-128-3p, which could be negatively regulated by miR-128-3p. Besides, miR-128-3p inhibition remarkably alleviated the inhibitory effects of HCl on the activation of ERK and PI3K/AKT pathways, which were further reversed after inhibition of miR-128-3p and E2F3 at the same time. Alltogether, our findings indicate that downregulation of microRNA-128-3p may protect human esophageal squamous cells Het-1A from HCl-induced cell injury via targeting E2F3 and inhibiting the activation of ERK and PI3K/AKT pathways. These findings provide the experimental basis for targeted treatment of reflux esophagitis.

Imperatorin protects H9c2 cardiomyoblasts cells from hypoxia/reoxygenation-induced injury through activation of ERK signaling pathway.

BACKGROUND: Imperatorin is a compound found in plants and has been widely used in Chinese medicine for many years. It has many pharmacological effects, including the recently reported anti-apoptotic function, however, the mechanism largely remains unclear. This study is aimed to elucidate the mechanism of Imperatorin's anti-apoptotic function. METHODS: A model of hypoxia and reoxygenation (H/R) treated h9c2 cardiomyoblasts was successfully constructed. The cells were treated with H/R condition, and followed by adding Imperatorin alone, Imperatorin with ERK inhibitor and/or ERK inhibitor alone, to examine the cell viability by Cell Counting Kit-8 assay, cell apoptosis rate by flow cytometry, and ERK expression by Western-blot under different conditions. RESULTS: The results showed that imperatorin exerted protective effect on h9c2 cells from H/R injure. It was also found that it not only increased cell viability but also reduced the apoptotic rate for H/R treated h9c2 cells. The experiments also demonstrated that imperatorin could upregulate the expression levels of both ERK1 and ERK2, which is a key step in ERK signaling pathway activation. CONCLUSIONS: These findings provided evidence that imperatorin could increase the cell viability and lower apoptotic rate in H/R treated h9c2 cells, and could also enhance the expression of ERK1/ERK2, demonstrating imperatorin's protective effect on H/R injured h9c2 cells through ERK signaling pathway.

Integration of Cine-cardiac Magnetic Resonance Radiomics and Machine Learning for Differentiating Ischemic and Dilated Cardiomyopathy.

RATIONALE AND OBJECTIVES: This study aims to evaluate the capability of machine learning algorithms in utilizing radiomic features extracted from cine-cardiac magnetic resonance (CMR) sequences for differentiating between ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM). MATERIALS AND METHODS: This retrospective study included 115 cardiomyopathy patients subdivided into ICM (n = 64) and DCM cohorts (n = 51). We collected invasive clinical (IC), noninvasive clinical (NIC), and combined clinical (CC) feature subsets. Radiomic features were extracted from regions of interest (ROIs) in the left ventricle (LV), LV cavity (LVC), and myocardium (MYO). We tested 10 classical machine learning classifiers and validated them through fivefold cross-validation. We compared the efficacy of clinical feature-based models and radiomics-based models to identify the superior diagnostic approach. RESULTS: In the validation set, the Gaussian naive Bayes (GNB) model outperformed the other models in all categories, with areas under the curve (AUCs) of 0.879 for IC_GNB, 0.906 for NIC_GNB, and 0.906 for CC_GNB. Among the radiomics models, the MYO_LASSOCV_MLP model demonstrated the highest AUC (0.919). In the test set, the MYO_RFECV_GNB radiomics model achieved the highest AUC (0.857), surpassing the performance of the three clinical feature models (IC_GNB: 0.732; NIC_GNB: 0.75; CC_GNB: 0.786). CONCLUSION: Radiomics models leveraging MYO images from cine-CMR exhibit promising potential for differentiating ICM from DCM, indicating the significant clinical application scope of such models. CLINICAL RELEVANCE STATEMENT: The integration of radiomics models and machine learning methods utilizing cine-CMR sequences enhances the diagnostic capability to distinguish between ICM and DCM, minimizes examination risks for patients, and potentially reduces the duration of medical imaging procedures.

Role of Multi-parameter-based Cardiac Magnetic Resonance in the Evaluation of Patients with Coronary Heart Disease Combined with Heart Failure.

BACKGROUND: Coronary Heart Disease (CHD) is one of the most common types of cardiovascular disease, and Heart Failure (HF) is an important factor in its progression. We aimed to evaluate the diagnostic value and predictors of multiparametric Cardiac Magnetic Resonance (CMR) in CHD patients with HF. METHODS: The study retrospectively included 145 CHD patients who were classified into CHD (HF+) (n = 91) and CHD (HF-) (n = 54) groups according to whether HF occurred. CMR assessed LV function, myocardial strain and T1 mapping. Multivariate linear regression analyses were performed to identify predictors of LV dysfunction, myocardial fibrosis, and LV remodeling. RESULTS: CHD (HF+) group had impaired strain, with increased native T1, ECV, and LVM index. The impaired strain was associated with LVM index (p < 0.05), where native T1 and ECV were affected by log-transformed amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. ROC analysis showed the combination of global circumferential strain (GCS), native T1, and LVM had a higher diagnostic value for the occurrence of HF in CHD patients.

Meanwhile, log-transformed NT-proBNP was an independent determinant of impaired strain, increased LVM index, native T1 and ECV. CONCLUSION: HF has harmful effects on LV systolic function in patients with CHD. In CHD (HF+) group, LV dysfunction is strongly correlated with the degree of LV remodeling and myocardial fibrosis. The combination of the three is more valuable in diagnosing HF than conventional indicators.

[Clinical application of 320-row computed tomography 4D digital subtraction angiography in hepatocellular carcinoma].

OBJECTIVE: To explore the application value of 320-row computed tomography (CT) 4D digital subtraction angiography (DSA) for hepatocellular carcinoma (HCC). METHODS: A total of 40 HCC patients received 320-row CT contrast scans. The 4D DSA images were obtained on the basis of baseline data. The normal anatomy and anatomical variations of hepatic artery, tumor supplying arteries, tumor vessels, tumor staining were observed by comparing DSA (n = 20). RESULTS: 320-row CT 4D DSA could show 6-7 levels of intrahepatic arterial branch. Normal hepatic artery anatomy was found in 35 cases (87.5%, Michels I type) and variations in 5 cases (12.5%). The diagnose accordance rate was 100% between 4D DSA and DSA in showing the anatomy and variation of hepatic artery. Among them, 320-row CT 4D DSA showed tumor staining (n = 40), tumor vessels (n = 28), tumor supplying arteries (n = 26) and two hepatic supplying arteries (n = 3). The number of tumor supplying arteries observed by 4D DSA (n = 20) was 18 versus 19 by DSA. Compared with DSA, the accurate rate of 4D DSA was 94.7% (18/19) in detecting tumor supplying arteries. CONCLUSION: As a noninvasive vascular examination modality, 320-row CT 4D DSA can accurately visualize normal anatomy and variation of hepatic artery, dynamically display tumor staining and reproducibly delineate the three-dimension relationship between tumor and blood vessels. In consistency with DSA in detection blood supply of HCC, 320-row CT 4D DSA provides a rapid, DSA-like and non-invasive alternative.

MiR-19b-3p regulated by BC002059/ABHD10 axis promotes cell apoptosis in myocardial infarction.

BACKGROUND: Recently, microRNAs (miRNAs), have been extensively investigated in diseases. The upregulated expression of miR-19b-3p has been validated in patients with hypertrophic cardiomyopathy. Nonetheless, it regulatory mechanism in myocardial infarction (MI) is still unclear. PURPOSE: This research aimed to investigate the role and molecular regulation mechanism of miR-19b-3p in MI. METHODS: QRT-PCR and western blot assays measured RNA and protein expression. Cell apoptosis were tested by flow cytometry and TUNEL assays. Cell viability was measured by trypan blue staining method. RIP and luciferase report assays examined gene interaction. The assays were performed under hypoxia condition. RESULTS: MiR-19b-3p was highly expressed in myocardial cell line H9C2, primary cardiomyocytes, and tissues from MI mouse model. MiR-19b-3p inhibition suppressed the apoptosis of cardiomyocytes. BC002059 could up-regulate ABHD10 through sequestering miR-19b-3p. BC002059 upregulation was observed to repress cell apoptosis. Rescue experiments demonstrated that miR-19b-3p overexpression abrogated the suppressive impact of BC002059 on the apoptosis of MI cells, and infarct size, area at risk as well as CK-MB and LDH release of MI mouse model tissues, which was further abolished via ABHD10 increment. CONCLUSION: MiR-19b-3p regulated by BC002059/ABHD10 axis promotes cell apoptosis in MI, which might provide a novel perspective for MI alleviation research.

Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation.

Endothelial cells are highly sensitive to hemodynamic shear stresses, which act in the blood flow's direction on the blood vessel's luminal surface. Thus, endothelial cells on that surface are exposed to various physiological and pathological stimuli, such as disturbed flow-induced shear stress, which may exert effects on adaptive vascular diameter or structural wall remodeling. Here we showed that plasma thioredoxin-interactive protein (TXNIP) and malondialdehyde levels were significantly increased in patients with slow coronary flow. In addition, human endothelial cells exposed to disturbed flow exhibited increased levels of TXNIP in vitro. On the other hand, deletion of human endothelial TXNIP increased capillary formation, nitric oxide production and mitochondrial function, as well as lessened oxidative stress response and endothelial cell inflammation. Additional beneficial impacts from TXNIP deletion were also seen in a glucose utilization study, as reflected by augmented glucose uptake, lactate secretion and extracellular acidification rate. Taken together, our results suggested that TXNIP is a key component involved in mediating shear stress-induced inflammation, energy homeostasis, and glucose utilization, and that TXNIP may serve as a potentially novel endothelial dysfunction regulator.

Comparison of Pharmacological Treatment Effects on Long-Time Outcomes in Heart Failure With Preserved Ejection Fraction: A Network Meta-analysis of Randomized Controlled Trials.

Beneficial effects of therapeutic drugs are controversial for heart failure with preserved ejection fraction (HFpEF). This meta-analysis aimed to evaluate and compare the interactive effects of different therapeutic drugs and placebo in patients with HFpEF. A comprehensive search was conducted using PubMed, Google Scholar, and Cochrane Central Register to identify related articles published before March 2021. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure (HF) hospitalization, and worsening HF events. A total of 14 randomized controlled trials, comprising 19,573 patients (intervention group, n = 9,954; control group, n = 9,619) were included in this network meta-analysis. All-cause mortality, cardiovascular mortality, and worsening HF events among therapeutic drugs and placebo with follow-up of 0.5-4 years were not found to be significantly correlated. The angiotensin receptor neprilysin inhibitor (ARNI) and angiotensin-converting enzyme inhibitor (ACEI) significantly reduced the HF hospitalizations compared with placebo (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.60-0.87 and HR 0.64, 95% CI 0.43-0.96, respectively), without heterogeneity among studies. The ARNI was superior to angiotensin receptor blocker (ARB) in reducing HF hospitalizations (HR 0.80, 95% CI 0.71-0.91), and vericiguat 10 mg ranked worse than beta-blockers for reducing all-cause mortality in patients with HFpEF (HR 3.76, 95% CI 1.06-13.32). No therapeutic drugs can significantly reduce mortality, but the ARNI or ACEI is associated with the low risk of HF hospitalizations for patients with HFpEF. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021247034.

Graphene-Assisted Electrochemical Sensor for Detection of Pancreatic Cancer Markers.

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.

C-Reactive Protein at Hospital Discharge and 1-Year Mortality in Acute Infective Endocarditis: A Prospective Observational Study.

Background: An accurate biomarker at hospital discharge is needed to identify patients with acute infective endocarditis (IE) who are at high risk of mortality. This prospective observational study evaluated the prognostic value of C-reactive protein (CRP). Methods: Patients with acute IE (n = 343) and hospitalized at 2 university-affiliated medical centers from January 2014 to December 2019 were enrolled. Patients were categorized as having low or high CRP (n = 217 and 126, respectively) at hospital discharge according to the optimal cutoff (CRP = 6.5 mg/L) determined via receiver-operating characteristic curve analysis. The primary endpoint was all-cause death, from hospital discharge to 1 year. The secondary endpoint was the cumulative rate of rehospitalization or paravalvular abscess at 1 year. Results: At the 12-month follow-up, the mortality rate of the high-CRP group (21.43%) was significantly higher than that of the low-CRP group (2.76%, log-rank P < 0.0001). The multivariate regression analysis indicated that the high-CRP group had a higher excess mortality hazard risk (HR = 4.182; 95% CI: 2.120, 5.211; P < 0.001). The cumulative 1-year incidence of paravalvular abscess of the high-CRP group (11.90%) was significantly higher than that of the low-CRP (5.07%; P = 0.022). The cumulative rate of heart rehospitalizations of the 2 groups were similar (18.25% cf. 14.29%, P = 0.273). Conclusion: For hospitalized patients with acute IE, a high CRP at discharge suggests a poor prognosis for 1-year mortality and paravalvular abscess.

LncRNA Kcnq1ot1 renders cardiomyocytes apoptosis in acute myocardial infarction model by up-regulating Tead1.

Acute myocardial infarction (AMI) is a major cardiovascular disease with high mortality worldwide. Hypoxia is a key inducing factor for AMI. We aimed to examine the expression and functions of Kcnq1ot1 (KCNQ1 overlapping transcript 1) in hypoxia-induced cardiomyocytes in the process of AMI. The left anterior descending coronary artery ligation (LAD) was used for inducing in-vivo AMI model and the primary cardiomyocytes were extracted; in-vitro H9c2 cell model was simulated by hypoxia treatment. TUNEL, flow cytometry and JC-1 assay were carried out to evaluate cell apoptosis. Mechanism assays including luciferase reporter assay and RIP assay revealed interplays between RNAs. To begin with, Kcnq1ot1 was revealed to be conspicuously upregulated in myocardium infracted zone and border zone within 2 days since establishment of the model. Moreover, inhibition of Kcnq1ot1 protected cardiomyocytes against hypoxia-triggered cell apoptosis during the process of AMI. Then, miR-466k and miR-466i-5p were proved to bind with Kcnq1ot1 and participated in Kcnq1ot1-mediated cardiomyocyte injury under hypoxia. Subsequently, Kcnq1ot1 was found to elevate Tead1 (TEA domain transcription factor 1) expression via sponging miR-466k and miR-466i-5p. Finally, it was verified that Kcnq1ot1 regulated hypoxia-induced cardiomyocyte injury dependent on Tead1. In conclusion, Kcnq1ot1 sponged miR-466k and miR-466i-5p to up-regulate Tead1, thus triggering cardiomyocyte injury in the process of AMI.

MicroRNA-505, Suppressed by Oncogenic Long Non-coding RNA LINC01448, Acts as a Novel Suppressor of Glycolysis and Tumor Progression Through Inhibiting HK2 Expression in Pancreatic Cancer.

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.

Pretreatment with bacterial components promotes DSS-injured colonic epithelial repair through the activation of STAT-3.

Bacterial protection and epithelial repair are important against inflammatory bowel disease (IBD). The present study was designed to examine the effects of different bacterial components on the repair of normal and dextran sodium sulfate (DSS)­treated colonic epithelial cells and the corresponding mechanisms. Human colonic epithelial cells (HT­29) were pretreated with various doses of LPS or CpG­dsDNA for 24 h and then treated with or without DSS for another 24 h. The epithelial repair was assessed by video analyses following mechanical injury. The epithelial expression of cluster of differentiation (CD)40 was assayed using flow cytometeric analysis. The production of interleukin (IL)­6 and tumor necrosis factor (TNF) in the cell culture medium were measured using ELISA. The expression of p38 mitogen­activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT)­3 were examined using western blot analysis and reverse transcription­quantitative polymerase chain reaction analysis. MAPK and STAT­3 inhibitors were also administrated to observe signaling­mediated repair. The results showed that pretreatment with lipopolysaccharide (LPS) or CpG­dsDNA promoted epithelial repair of the DSS­treated cells. The promoting effects were associated with the downregulation of CD40 molecules, inhibition of the p38 MAPK/TNFα pathway and activation of the STAT3/IL­6 pathway. The STAT3 inhibitor abrogated the protective effects of LPS and CpG­dsDNA on wound repair. These results demonstrated that LPS and CpG­dsDNA induced preadaptation to DSS injury. This preadaptation was accompanied by the activation of STAT­3. Thus, bacterial components may be used as a strategy for the therapeutic prevention of IBD.

Relationship of SELE A561C and G98T Variants With the Susceptibility to CAD.

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.

Chemerin Stimulates Vascular Smooth Muscle Cell Proliferation and Carotid Neointimal Hyperplasia by Activating Mitogen-Activated Protein Kinase Signaling.

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.

Complete mitochondrial genome of Rhipicephalus simus.

In this study, we report the basic characteristics of the Rhipicephalus simus mitochondrial genome, including structural organization and base composition of the rRNAs, tRNAs and protein-coding genes. The total length of the mitogenome was 14,929 bp, included 37 genes and with a genome structure similar to other ticks.