Wheat PHT1;9 acts as one candidate arsenate absorption transporter for phytoremediation.

Arsenate (AsV) is one of the most common forms of arsenic (As) in environment and plant high-affinity phosphate transporters (PHT1s) are the primary plant AsV transporters. However, few PHT1s involved in AsV absorption have been identified in crops. In our previous study, TaPHT1;3, TaPHT1;6 and TaPHT1;9 were identified to function in phosphate absorption. Here, their AsV absorption capacities were evaluated using several experiments. Ectopic expression in yeast mutants indicated that TaPHT1;9 had the highest AsV absorption rates, followed by TaPHT1;6, while not for TaPHT1;3. Under AsV stress, further, BSMV-VIGS-mediated TaPHT1;9-silencing wheat plants exhibited higher AsV tolerance and lower As concentrations than TaPHT1;6-silenced plants, whereas TaPHT1;3-silencing plants had similar phenotype and AsV concentrations to control. These suggested that TaPHT1;9 and TaPHT1;6 possessed AsV absorption capacity with the former showing higher activities. Under hydroponic condition, furthermore, CRISPR-edited TaPHT1;9 wheat mutants showed the enhanced tolerance to AsV with decreased As distributions and concentrations, whereas TaPHT1;9 ectopic expression transgenic rice plants had the opposite results. Also, under AsV-contaminated soil condition, TaPHT1;9 transgenic rice plants exhibited depressed AsV tolerance with increased As concentrations in roots, straws and grains. Moreover, Pi addition alleviated the AsV toxicity. These suggested that TaPHT1;9 should be a candidate target gene for AsV phytoremediation.

Long non-coding RNA SENCR alleviates endothelial-to-mesenchymal transition via targeting miR-126a.

Introduction: Long non-coding RNAs (lncRNAs) constitute a growing class of non-coding genes with diverse cellular function. Recent studies have reported that lncRNA smooth muscle and endothelial cell-enriched (SENCR) was associated with the phenotype switch of vascular smooth muscle cells and participated in vascular homeostasis. However, the potential role of SENCR in endothelial-to-mesenchymal transition (EndMT) and the underlying mechanism remain unknown. Material and methods: Human carotid plaque samples and human coronary endothelial cells (HACECs) were collected to examine the expression of SENCR. Quantitative PCR and immunoblots were performed to evaluate the expression of SENCR and miR-126a in HACECs in response to TGF-ß1 and transfected with small interfering RNA. Results: We found that SENCR was significantly decreased in carotid plaques as compared to normal carotids. Knockdown of SENCR in HACECs aggravated the expression of smooth muscle markers α-SMA and calponin induced by TGF-ß1 but repressed the expression of endothelial markers platelet/endothelial cell adhesion molecule 1 (PECAM1) and VE-cadherin down-regulated by TGF-ß1. Through bioinformatic analysis and Luciferase assay, miR-126a was identified as the direct target of SENCR. Further mechanistic experiments revealed that overexpression of miR-126a bound to the 3'UTR region of SMURF2 and inhibited the expression of SMURF2, which was considered as the negative regulator of TGF-ß/Smad signaling. Finally, overexpression of miR-126a did not restore the decreased expression of the smooth muscle markers α-SMA and calponin under the condition of SMURF2 depletion, suggesting that the effect of miR-126a on EndMT progression is SMURF2 dependent. Conclusions: SENCR alleviates TGF-ß-induced EndMT and sponges miR-126a expression via direct inhibition of the negative regulator of TGF-ß/Smad signaling SMURF2.

Interleukin-27 ameliorates coxsackievirus-B3-induced viral myocarditis by inhibiting Th17 cells.

BACKGROUND: Interleukin (IL)-27, which has both pro and anti- inflammatory properties, is a new discovered heterodimeric cytokine that belongs to IL-12 family. However, the expression pattern and functional role of IL-27 in viral myocarditis (VMC) has not been investigated. METHODS: BALB/c mice were intraperitoneally (i.p) infected with Coxsackie virus B3 (CVB3) for establishing VMC models. Mice were then injected i.p. with Anti-Mouse IL-27 p28Ab or recombinant IL-27 for neutralization and overexpression of IL-27. The survival rates of mice were recorded and the kinetics of IL-27 expression, the frequencies of Th17 cells and the expression of inflammatory cytokine in CVB3-infected mice were determined by ELISA, real-time PCR and flow cytometry. RESULTS: The IL-27 expression in heart tissues and serum in coxsackievirus B3 (CVB3)-induced myocarditis mice peaked on day 4 but then rapidly decreased during the late infectious stage of CVB3, high IL-27 levels were negatively correlated with bodyweight loss (r = -0.71, P = 0.021) and myocardial pathological score (r = -0.85, P = 0.0018). Additionally, neutralization of IL-27 with Anti-IL-27 Ab accelerated, whereas systemic administration of recombinant mouse IL-27 ameliorated CVB3-induced myocarditis. The protective role of IL-27 in VMC was reflected by an improved survival rate, increased bodyweights, and reduced pathological scores in Anti-IL-27 group compared with IgG control group. Mechanistic investigations showed that IL-27 inhibited Th17 cells frequencies and IL-17 production, as well as the Th17-related proinflammatory cytokines in heart tissues. CONCLUSIONS: Our results demonstrate that that IL-27 effectively protects the myocardium from the pathogenesis of CVB3 induced myocarditis, which may be attributable to reduced Th17 production. IL-27 might serve as a novel therapeutic treatment for VMC.