Association of elevated circulating monocyte-platelet aggregates with hypercoagulability in patients with nephrotic syndrome.

BACKGROUND: Hypercoagulability emerges as a central pathological feature and clinical complication in nephrotic syndrome. Increased platelet activation and aggregability are closely related to hypercoagulability in nephrotic syndrome. Monocyte-platelet aggregates (MPAs) have been proposed to represent a robust biomarker of platelet activation. The aim of this study was to investigate levels of the circulating MPAs and MPAs with the different monocyte subsets to evaluate the association of MPAs with hypercoagulability in nephrotic syndrome. METHODS: Thirty-two patients with nephrotic syndrome were enrolled. In addition, thirty-two healthy age and sex matched adult volunteers served as healthy controls. MPAs were identified by CD14 monocytes positive for CD41a platelets. The classical (CD14 + + CD16-, CM), the intermediate (CD14 + + CD16+, IM) and the non-classical (CD14 + CD16++, NCM) monocytes, as well as subset specific MPAs, were measured by flow cytometry. RESULTS: Patients with nephrotic syndrome showed a higher percentage of circulating MPAs as compared with healthy controls (p < 0.001). The percentages of MPAs with CM, IM, and NCM were higher than those of healthy controls (p = 0.012, p < 0.001 and p < 0.001, respectively). Circulating MPAs showed correlations with hypoalbuminemia (r=-0.85; p < 0.001), hypercholesterolemia (r = 0.54; p < 0.001), fibrinogen (r = 0.70; p < 0.001) and D-dimer (r = 0.37; p = 0.003), but not with hypertriglyceridemia in nephrotic syndrome. The AUC for the prediction of hypercoagulability in nephrotic syndrome using MPAs was 0.79 (95% CI 0.68-0.90, p < 0.001). The sensitivity of MPAs in predicting hypercoagulability was 0.71, and the specificity was 0.78. CONCLUSION: Increased MPAs were correlated with hypercoagulability in nephrotic syndrome. MPAs may serve as a potential biomarker for thrombophilic or hypercoagulable state and provide novel insight into the mechanisms of anticoagulation in nephrotic syndrome.

Ventricular fibrillation induced by fever in structurally normal hearts.

Ventricular fibrillation (VF) is a life-threatening arrhythmia that usually happens in patients with structural heart diseases. However, fever-induced ventricular fibrillation in structurally normal hearts was reported, and the four main diseases associated with these cases were Brugada syndrome, long QT syndrome, idiopathic ventricular fibrillation, and non-cardiovascular diseases. In this review, we analyzed this phenomenon and its clinical characteristics.

MicroRNA-155 inhibition attenuates myocardial infarction-induced connexin 43 degradation in cardiomyocytes by reducing pro-inflammatory macrophage activation.

Background: Degradation of pro-inflammatory macrophage-mediated connexin 43 (Cx43) plays an important role in post-myocardial infarction (MI) arrhythmogenesis, microRNA (miR)-155 produced by macrophages has been shown to mediate post-MI effects. We hypothesized that miR-155 inhibition attenuated MI-induced Cx43 degradation by reducing pro-inflammatory macrophage activation. Methods: MI was induced by permanent ligation of the left anterior descending coronary artery in male C57BL/6 mice. Lipopolysaccharide (LPS)-stimulated mice bone marrow-derived macrophages (BMDMs) and hypoxia-induced neonatal rat cardiomyocytes (NRCMs) were used in vitro models. qRT-PCR, Western-blot and immunofluorescence were used to analyze relevant indicators. Results: The expression levels of miR-155, interleukin-1 beta (IL-1ß), and matrix metalloproteinase (MMP)7 were higher in MI mice and LPS-treated BMDMs than in the sham/control groups, treatment with a miR-155 antagomir reversed these effects. Moreover, miR-155 inhibition reduced ventricular arrhythmias incidence and improved cardiac function in MI mice. Cx43 expression was decreased in MI mice and hypoxia-exposed NRCMs, and hypoxia-induced Cx43 degradation in NRCMs was reduced by application of conditioned medium from LPS-induced BMDMs treated with the miR-155 antagomir, but increased by conditioned medium from BMDMs treated with a miR-155 agomir. Importantly, NRCMs cultured in conditioned medium from LPS-induced BMDMs transfected with small interfering RNA against IL-1ß and MMP7 showed decreased hypoxia-mediated Cx43 degradation, and this effect also was diminished by BMDM treatment with the miR-155 agomir. Additionally, siRNA-mediated suppressor of cytokine signaling 1 (SOCS1) knockdown in LPS-induced BMDMs promoted Cx43 degradation in hypoxia-exposed NRCMs, and the effect was reduced by the miR-155 inhibition. Conclusions: MiR-155 inhibition attenuated post-MI Cx43 degradation by reducing macrophage-mediated IL-1ß and MMP7 expression through the SOCS1/nuclear factor-κB pathway.

Molecular identification and expression patterns of odorant binding protein and chemosensory protein genes in Athetis lepigone (Lepidoptera: Noctuidae).

The olfaction system of insects plays an important role in mediating various physiological behaviors, including locating hosts, avoiding predators, and recognizing mates and oviposition sites. Therefore, some key genes in the system present valuable opportunities as targets for developing novel green pesticides. Athetis lepigone, a noctuid moth can feed on more than 30 different host plants making it a serious polyphagous pest worldwide, and it has become one of the major maize pests in northern China since 2011. However, there are no reports on effective and environmentally friendly pesticides for the control of this pest. In this study, we identified 28 genes encoding putative odorant binding proteins (OBPs) and 20 chemosensory protein (CSPs) genes based on our previous A. lepigone transcriptomic data. A tissue expression investigation and phylogenetic analysis were conducted in an effort to postulate the functions of these genes. Our results show that nearly half (46.4%) of the AlOBPs exhibited antennae-biased expression while many of the AlCSPs were highly abundant in non-antennal tissues. These results will aid in exploring the chemosensory mechanisms of A. lepigone and developing environmentally friendly pesticides against this pest in the future.

TBX5 mutations contribute to early-onset atrial fibrillation in Chinese and Caucasians.

AIMS: Atrial fibrillation (AF) is a common arrhythmia with an important heritable aspect. The genetic factors underlying AF have not been fully elucidated. METHODS AND RESULTS: We screened six candidate genes (CAV1, KCNJ2, KCNQ1, NKX2.5, PITX2, and TBX5) for novel mutations in 139 patients of Chinese descent with early-onset AF and 576 controls. Four missense TBX5 mutations, p.R355C, p.Q376R, p.A428S, and p.S372L, were identified in evolutionarily conserved regions. We did not find any mutations in CAV1, KCNJ2, KCNQ1, NKX2.5, and PITX2. These mutations increased the expression of atrial natriuretic peptide (ANP) and connexin-40 (CX40) in the primarily cultured rat atrial myocytes but did not alter the expression of cardiac structural genes, atrial myosin heavy chain-α (MHC-α) and myosin light chain-2α (MLC-2α). Overexpression of p.R355C developed an atrial arrhythmia suggestive of paroxysmal AF in the zebrafish model. To replicate our findings, we screened TBX5 in 527 early-onset AF cases from the Massachusetts General Hospital AF study. A novel TBX5 deletion (ΔAsp118, p.D118del) was identified, while no TBX5 mutations were identified in 1176 control subjects. CONCLUSION: Our results provide both genetic and functional evidence to support the contribution of TBX5 gene in the pathogenesis of AF. The potential mechanism of arrhythmia may be due in part to the disturbed expression of ANP and CX40.

An analysis of the Athetis lepigone transcriptome from four developmental stages.

Athetis lepigone Möschler (Lepidoptera: Noctuidae) has recently become an important insect pest of maize (Zea mays) crops in China. In order to understand the characteristics of the different developmental stages of this pest, we used Illumina short-read sequences to perform de novo transcriptome assembly and gene expression analysis for egg, larva, pupa and adult developmental stages. We obtained 10.08 Gb of raw data from Illumina sequencing and recovered 81,356 unigenes longer than 100 bp through a de novo assembly. The total sequence length reached 49.75 Mb with 858 bp of N50 and an average unigene length of 612 bp. Annotation analysis of predicted proteins indicate that 33,736 unigenes (41.47% of total unigenes) are matches to genes in the Genbank Nr database. The unigene sequences were subjected to GO, COG and KEGG functional classification. A large number of differentially expressed genes were recovered by pairwise comparison of the four developmental stages. The most dramatic differences in gene expression were found in the transitions from one stage to another stage. Some of these differentially expressed genes are related to cuticle and wing formation as well as the growth and development. We identified more than 2,500 microsatellite markers that may be used for population studies of A. lepigone. This study lays the foundation for further research on population genetics and gene function analysis in A. lepigone.

Polymorphisms but not mutations of the KCNQ1 gene are associated with lone atrial fibrillation in the Chinese Han population.

BACKGROUND: Recent studies suggest that mutation of the slow delayed rectifier potassium channel (IKs) contributes to familial atrial fibrillation (FAF). In the current study, we identified common genetic variants of KCNQ1 and explored the potential association between KCNQ1 polymorphism with lone AF (LAF). METHODS: Clinical data and blood samples were collected from 190 Han Chinese patients with sporadic AF and matched healthy controls. Variants of the KCNQ1 gene were identified using single-strand conformational polymorphism (SSCP) analysis. A case-control association study in KCNQ1 identified six known single-nucleotide polymorphisms (SNPs) during SSCP screening of the 190 LAF patients and 190 healthy controls. RESULTS: One of the SNPs in KCNQ1 was strongly associated with LAF; significant allelic association was detected rs59233444 (P = 0.013, OR = 1.469, 95% confidence interval (CI): 1.083-1.993). A multiple regression analysis indicated that rs59233444 is an independent risk factor for LAF. Twelve new variants were identified in KCNQ1, including one in the 5'-UTR, two in the 3'-UTR, six in introns, two synonymous substitutions, and one missense substitution. Variants c.1009C>T, c.1860C>T, and c.+2285C>T were not present in the 190 controls, and the others were identified in controls at various frequencies. CONCLUSIONS: rs59233444, a common SNP but not mutation in the coding regions of the KCNQ1 gene, is a risk factor for LAF in Chinese Han population.

The effects of temperature on the development of the moth Athetis lepigone, and a prediction of field occurrence.

Athetis lepigone (Möschler) (Lepidoptera: Noctuidae) is an important insect pest of corn crops in China. To determine the effect of temperature on A. lepigone growth, and to provide a forecasting model for this pest, the development and fecundity of A. lepigone under five different temperatures (18, 21, 24, 27, 30 °C) was investigated, and an experimental population life table was constructed based on the obtained results. The results showed that the duration of development of A. lepigone decreased as the temperature increased from 18 to 30 °C. Approximately 95% of mature larvae stopped pupating at 18 °C, and about 70% of mature larvae stopped pupating at 21 °C. When the growth chamber temperature was above 24 °C, no growth arrest was observed. The results indicated that the optimum growth temperature of A. lepigone was about 26.47 °C. In this study, the highest survival rate, fecundity per female, and population index trend were observed when the temperature was set at 27 °C. The percentages of larvae that could spin cocoons after the 5th or 6th instar differed at the different temperatures. The developmental threshold temperatures for A. lepigone eggs, larvae, pre-pupae, pupae, preoviposition females, and the whole generation (i.e., egg to oviposition) were 11.03, 9.04, 15.08, 11.79, 11.63, and 10.84 °C, respectively, and their effective accumulative temperatures were 63.51, 339.42, 30.04, 118.41, 35.06 and 574.08 degree-days, respectively. Based on the effective accumulative temperature law, this pest insect can have four generations in most of the Huang-Huai region of China, and two to three generations annually in some cold regions. Athetis lepigone may have four generations in the mid-southern part of Hebei Province. This prediction matches the field survey results.