Protective effects of Naringin in a rat model of spinal cord ischemia–reperfusion injury

Purpose: To evaluate the activity of naringin (NAR) in a rat model of spinal cord ischemic injury (SCII).Methods: Forty female rats were randomized into four groups: saline without  occlusion (control; group I), SCII (group II), 50 mg/kg NAR (group III), or 100 mg/kg NAR (group IV) for 7 days prior to SCI insult (pre-treatment). Neurological and locomotor functions, antioxidant activity, edema and inflammatory markers were determined.Results: Pre-treatment with NAR considerably lowered the incidence of spinal edema, lipid peroxidation products, and inflammatory markers (TNF-α, NF-p65, IL-1β, and IL-6). It also successfully reverted the antioxidative activity to near-normal levels and improved locomotor function by protecting spinal tissue from oxidative damage and inflammatory insults. NAR administration effectively downregulated the protein expression of TNF-α and NF-κB p65 subunit in spinal tissue, thus confirming its antiinflammatory activity.Conclusion: The results suggests that NAR exhibits neuroprotective effects by inhibiting free radical generation and downregulating inflammatory markers in an SCI rat model.Keywords: Naringin, Spinal cord injury, Locomotor function, Edema, Oxidative  stress, Inflammatio

Aspirin for Primary Prevention of Cardiovascular Events: Meta-Analysis of Randomized Controlled Trials and Subgroup Analysis by Sex and Diabetes Status

Objective: To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status. Methods: We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12. Results: Fourteen trials (107,686 participants) were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85–0.95), myocardial infarction (0.86; 0.75–0.93), ischemic stroke (0.86; 0.75–0.98) and all-cause mortality (0.94; 0.89–0.99). There were also increases in hemorrhagic stroke (1.34; 1.01–1.79) and major bleeding (1.55; 1.35–1.78) with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59–0.85) and ischemic stroke among women (0.77; 0.63–0.93). Aspirin use was associated with a reduction (0.65; 0.51–0.82) in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day) were as large as those obtained with higher doses (650 mg/day). Conclusions: The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials

Increased MicroRNA-146a Levels in Plasma of Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Background: MicroRNAs (miRNAs), a class of small non-coding RNAs, are thought to serve as crucial regulators of gene expression. Dysregulated expression of miRNAs has been described in various diseases and may contribute to related pathologic processes. Our aim was to examine circulating miRNA-146a levels in newly diagnosed type 2 diabetes mellitus (new-T2DM) patients from a Chinese Han population. Methodology/Principal Findings Circulating miRNA-146a was extracted from plasma samples of 90 new-T2DM patients and 90 age- and sex-matched controls. Quantitative PCR assessment revealed that circulating miRNA-146a levels were significantly elevated in new-T2DM patients compared with controls. Participants in the highest tertile of circulating miRNA-146a levels showed a notably higher risk for new-T2DM (crude OR 4.333, 95% CI, 1.935 to 9.705, P = 0.001) than persons in the lowest tertile. Controlling for known risk factors and some biochemical indicators did not attenuate the aforementioned association. In addition, receiver operating characteristic (ROC) curves generated for miRNA-146a revealed an area under the curve (AUC) of 0.725 (95% CI, 0.651 to 0.799, P < 0.001). Moreover, higher circulating miRNA-146a levels were significantly associated with higher plasma heme oxygenase-1 (HO-1) concentrations (β coefficient = 0.131, P < 0.001) and lower HOMA-beta (β coefficient = -0.153, P = 0.015). Conclusions/Significance: We found that circulating miRNA-146a levels were significantly elevated in new-T2DM patients compared with healthy controls. Whether expression of circulating miRNA-146a holds predictive value for T2DM warrants further investigations

Association Analysis and Identification of ZmHKT1;5 Variation With Salt-Stress Tolerance

The high-affinity potassium transporter (HKT) genes are essential for plant salt stress tolerance. However, there were limited studies on HKTs in maize (Zea mays), and it is basically unknown whether natural sequence variations in these genes are associated with the phenotypic variability of salt tolerance. Here, the characterization of ZmHKT1;5 was reported. Under salt stress, ZmHKT1;5 expression increased strongly in salt-tolerant inbred lines, which accompanied a better-balanced Na+/K+ ratio and preferable plant growth. The association between sequence variations in ZmHKT1;5 and salt tolerance was evaluated in a diverse population comprising 54 maize varieties from different maize production regions of China. Two SNPs (A134G and A511G) in the coding region of ZmHKT1;5 were significantly associated with different salt tolerance levels in maize varieties. In addition, the favorable allele of ZmHKT1; 5 identified in salt tolerant maize varieties effectively endowed plant salt tolerance. Transgenic tobacco plants of overexpressing the favorable allele displayed enhanced tolerance to salt stress better than overexpressing the wild type ZmHKT1;5. Our research showed that ZmHKT1;5 expression could effectively enhance salt tolerance by maintaining an optimal Na+/K+ balance and increasing the antioxidant activity that keeps reactive oxygen species (ROS) at a low accumulation level. Especially, the two SNPs in ZmHKT1;5 might be related with new amino acid residues to confer salt tolerance in maize.Key Message: Two SNPs of ZmHKT1;5 related with salt tolerance were identified by association analysis. Overexpressing ZmHKT1;5 in tobaccos showed that the SNPs might enhance its ability to regulating Na+/K+ homeostasis

The Formation and Evolution of Interorganisational Business Networks in Megaprojects: A Case Study of Chinese Skyscrapers

Megaprojects are implemented by different organisations, such as owners, consultants, and contractors. Gradually, these organisations and their connections can form business networks that influence both the market position of individual organisations and project performance. Previous research on large-scale projects mainly focused on static and homogeneous networks that were constructed by one individual project and/or carried out over one-off collaboration. However, this neglected the consideration of project network diversity, as well as repetitive, dynamic, cross-project coopetition relationship (i.e., collaboration and competition) and long-term business networks formed by key actors. Here, we chose Chinese skyscrapers over 300 meters that were built from 1996 to 2015 as typical megaproject cases and analysed the formation and evolution of megaproject business networks from the perspective of interorganisational coopetition. We identified the key actors involved and empirically studied their dynamic network positions over time. The main contributions of this study are threefold. First, we found that past collaboration experience has direct and dynamic impacts on the formation of megaproject business networks. Second, we identified key actors in the interorganisational business network and unveiled their dynamic positions with clear patterns. Third, we highlighted the temporal-spatial effect on the formation and development of business networks, alongside developments in the megaproject market. The findings of this study also provide practical applications for owners to choose collaboration partners and to build high-performance teams and for suppliers to enter and sustain the business in the megaprojects networks