NADPH oxidase-derived reactive oxygen species in cardiac pathophysiology

Chronic heart failure, secondary to left ventricular hypertrophy or myocardial infarction, is a condition with increasing morbidity and mortality. Although the mechanisms underlying the development and progression of this condition remain a subject of intense interest, there is now growing evidence that redox-sensitive pathways play an important role. This article focuses on the involvement of reactive oxygen species derived from a family of superoxide-generating enzymes, termed NADPH oxidases (NOXs), in the pathophysiology of ventricular hypertrophy, the accompanying interstitial fibrosis and subsequent heart failure. In particular, the apparent ability of the different NADPH oxidase isoforms to define the response of a cell to a range of physiological and pathophysiological stimuli is reviewed. If confirmed, these data would suggest that independently targeting different members of the NOX family may hold the potential for therapeutic intervention in the treatment of cardiac disease.     

Saccharide-mediated antagonistic effects of bark beetle fungal associates on larvae

Bark beetles are among the most destructive of pine forest pests and they form close symbiotic relationships with ophiostomatoid fungi. Although some fungi are considered to be mutualistic symbionts of bark beetles with respect to the supply of nutrients, detrimental effects of fungal symbionts on larval growth have also been frequently reported. The mechanisms of such antagonistic effects are hypothesized to be a decrease in nutritional resources caused by competition for saccharides by the fungi. Here, we provide experimental evidence that three beetle-associated fungi modify the nutritional content of an artificial phloem diet, leading to a detrimental effect on the growth of Dendroctonus valens larvae. When larvae were fed a diet of pine phloem in agar medium colonized with any of these fungi, feeding activity was not affected but weight significantly decreased. Additional analysis showed that fungi depleted the fructose and glucose concentrations in the phloem media. Furthermore, these detrimental effects were neutralized by supplementing the media with fructose or glucose, suggesting that fungi may affect larval growth by modifying diet saccharide contents. These data indicate that fungus-induced nutritional changes in bark beetle diet can affect larval growth, and that the mechanism involves fungus-induced saccharide depletion from the larval diet.     

Prognostic Impact of IPSS-R and Chromosomal Translocations in 751 Korean Patients with Primary Myelodysplastic Syndrome

Chromosomal translocations are rare in myelodysplastic syndrome (MDS) and their impact on overall survival (OS) and response to hypomethylating agents (HMA) is unknown. The prognostic impact of the revised International Prognostic Scoring System (IPSS-R) and for chromosomal translocations was assessed in 751 patients from the Korea MDS Registry. IPSS-R effectively discriminated patients according to leukaemia evolution risk and OS. We identified 40 patients (5.3%) carrying translocations, 30 (75%) of whom also fulfilled complex karyotype criteria. Translocation presence was associated with a shorter OS (median, 12.0 versus 79.7 months, P < 0.01). Multivariate analysis demonstrated that translocations (hazard ratio [HR] 1.64 [1.06–2.63]; P = 0.03) as well as age, sex, IPSS-R, and CK were independent predictors of OS. In the IPSS-R high and very high risk subgroup (n = 260), translocations remained independently associated with OS (HR 1.68 [1.06–2.69], P = 0.03) whereas HMA treatment was not associated with improved survival (median OS, 20.9 versus 21.2 months, P = 0.43). However, translocation carriers exhibited enhanced survival following HMA treatment (median 2.1 versus 12.4 months, P = 0.03). Our data suggest that chromosomal translocation is an independent predictor of adverse outcome and has an additional prognostic value in discriminating patients with MDS having higher risk IPSS-R who could benefit from HMA treatment.     

Copper promotes the migration of bone marrow mesenchymal stem cells via Rnd3-dependent cytoskeleton remodeling

The motility of mesenchymal stem cells (MSCs) is highly related to their homing in vivo, a critical issue in regenerative medicine. Our previous study indicated copper (Cu) might promote the recruitment of endogenous MSCs in canine esophagus defect model. In this study, we investigated the effect of Cu on the motility of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanism in vitro. Cu supplementation could enhance the motility of BMSCs, and upregulate the expression of hypoxia-inducible factor 1α (Hif1α) at the protein level, and upregulate the expression of rho family GTPase 3 (Rnd3) at messenger RNA and protein level. When Hif1α was silenced by small interfering RNA (siRNA), Cu-induced Rnd3 upregulation was blocked. When Rnd3 was silenced by siRNA, the motility of BMSCs was decreased with or without Cu supplementation, and Cu-induced cytoskeleton remodeling was neutralized. Furthermore, overexpression of Rnd3 also increased the motility of BMSCs and induced cytoskeleton remodeling. Overall, our results demonstrated that Cu enhanced BMSCs migration through, at least in part, cytoskeleton remodeling via Hif1α-dependent upregulation of Rnd3. This study provided an insight into the mechanism of the effect of Cu on the motility of BMSCs, and a theoretical foundation of applying Cu to improve the recruitment of BMSCs in tissue engineering and cytotherapy.     

Photoacoustic Imaging of Breast Microcalcifications: A Preliminary Study with 8-Gauge Core-Biopsied Breast Specimens

Background

We presented the photoacoustic imaging (PAI) tool and to evaluate whether microcalcifications in breast tissue can be detected on photoacoustic (PA) images.

Methods

We collected 21 cores containing microcalcifications (n = 11, microcalcification group) and none (n = 10, control group) in stereotactic or ultrasound (US) guided 8-gauge vacuum-assisted biopsies. Photoacoustic (PA) images were acquired through ex vivo experiments by transmitting laser pulses with two different wavelengths (700 nm and 800 nm). The presence of microcalcifications in PA images were blindly assessed by two radiologists and compared with specimen mammography. A ratio of the signal amplitude occurring at 700 nm to that occurring at 800 nm was calculated for each PA focus and was called the PAI ratio.

Results

Based on the change of PA signal amplitude between 700 nm and 800 nm, 10 out of 11 specimens containing microcalcifications and 8 out of 10 specimens without calcifications were correctly identified on blind review; the sensitivity, specificity, accuracy, positive predictive and negative predictive values of our blind review were 90.91%, 80.0%, 85.71%, 83.33% and 88.89%. The PAI ratio in the microcalcification group was significantly higher than that in the control group (the median PAI ratio, 2.46 versus 1.11, respectively, P = .001). On subgroup analysis in the microcalcification group, neither malignant diagnosis nor the number or size of calcification-foci was proven to contribute to PAI ratios.

Conclusion

Breast microcalcifications generated distinguishable PA signals unlike breast tissue without calcifications. So, PAI, a non-ionizing and non-invasive hybrid imaging technique, can be an alternative in overcoming the limitations of conventional US imaging.     

沙打旺组织培养中脱分化细胞的超微结构及细胞核的动态变化

对沙打旺的下胚轴、子叶、幼叶组织培养中脱分化细胞进行了超微结构观察,并着重讨论了细胞核的动态变化。脱分化细胞的细胞质中线粒体墙加,嵴明显;多聚核糖体增多;高尔基体增加;质体中积累淀粉。核仁与核内异染色质之间有一个动态过程。此过程暂称“核仁物质喷射“现象。在致有以下：１．核体出现,半嵌在增大的核仁上,核内异染色质沿核膜凝聚;２．异染色质移向核仁,并与核仁接触,核体消失,部分异质进入核仁;３．核仁物质     

Emotional States Modulate the Recognition Potential during Word Processing

This study examined emotional modulation of word processing, showing that the recognition potential (RP), an ERP index of word recognition, could be modulated by different emotional states. In the experiment, participants were instructed to compete with pseudo-competitors, and via manipulation of the outcome of this competition, they were situated in neutral, highly positive, slightly positive, highly negative or slightly negative emotional states. They were subsequently asked to judge whether the referent of a word following a series of meaningless character segmentations was an animal or not. The emotional induction task and the word recognition task were alternated. Results showed that 1) compared with the neutral emotion condition, the peak latency of the RP under different emotional states was earlier and its mean amplitude was smaller, 2) there was no significant difference between RPs elicited under positive and negative emotional states in either the mean amplitude or latency, and 3) the RP was not affected by different degrees of positive emotional states. However, compared to slightly negative emotional states, the mean amplitude of the RP was smaller and its latency was shorter in highly negative emotional states over the left hemisphere but not over the right hemisphere. The results suggest that emotional states influence word processing.     

Effects of Cortisol and Dexamethasone on Insulin Signalling Pathways in Skeletal Muscle of the Ovine Fetus during Late Gestation

Before birth, glucocorticoids retard growth, although the extent to which this is mediated by changes in insulin signalling pathways in the skeletal muscle of the fetus is unknown. The current study determined the effects of endogenous and synthetic glucocorticoid exposure on insulin signalling proteins in skeletal muscle of fetal sheep during late gestation. Experimental manipulation of fetal plasma glucocorticoid concentration was achieved by fetal cortisol infusion and maternal dexamethasone treatment. Cortisol infusion significantly increased muscle protein levels of Akt2 and phosphorylated Akt at Ser473, and decreased protein levels of phosphorylated forms of mTOR at Ser2448 and S6K at Thr389. Muscle GLUT4 protein expression was significantly higher in fetuses whose mothers were treated with dexamethasone compared to those treated with saline. There were no significant effects of glucocorticoid exposure on muscle protein abundance of IR-β, IGF-1R, PKCζ, Akt1, calpastatin or muscle glycogen content. The present study demonstrated that components of the insulin signalling pathway in skeletal muscle of the ovine fetus are influenced differentially by naturally occurring and synthetic glucocorticoids. These findings may provide a mechanism by which elevated concentrations of endogenous glucocorticoids retard fetal growth.