Vasostatin Inhibits VEGF-Induced Endothelial Cell Proliferation, Tube Formation and Induces Cell Apoptosis under Oxygen Deprivation

Anti-angiogenesis treatment has been a promising new form of cancer therapy. Endothelial cells are critical for vascular homeostasis and play important roles in angiogenesis, vascular and tissue remodeling. Vasostatin, the 180 amino acid N-terminal fragment of the calreticulin protein, is reported to be a potent endogenous inhibitor of angiogenesis, suppressing tumor growth. However, the mechanism of these effects has not been sufficiently investigated. This study was performed to investigate the possible mechanism of vasostatin effects on primary cultured human umbilical vein endothelial cells (HUVEC). We found that vasostatin could inhibit the cell viability of HUVEC and induce cell apoptosis through mitochondrial pathways via activation of caspase-3 under oxygen deprivation conditions. Meanwhile, vasostatin also inhibited vascular endothelial growth factor-induced proliferation and tube formation of HUVEC. The possible mechanism of vasostatin-inhibited proliferation of HUVEC could be through down-regulation of endothelial nitric oxide synthase. These findings suggest that vasostatin could regulate endothelial cell function and might be used in anti-angiogenesis treatment

Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts.

Overexposure of the fetus to glucocorticoids in gestation is detrimental to fetal development. The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG) plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) or p38 mitogen-activated protein kinase (MAPK) pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP) could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression

<i>GmWRKY81</i> Encoding a WRKY Transcription Factor Enhances Aluminum Tolerance in Soybean

Aluminum (Al) toxicity is an essential factor that adversely limits soybean (Glycine max (L.) Merr.) growth in acid soils. WRKY transcription factors play important roles in soybean responses to abiotic stresses. Here, GmWRKY81 was screened from genes that were differentially expressed under Al treatment in Al-tolerant soybean Baxi10 and Al-sensitive soybean Bendi2. We found that GmWRKY81 was significantly induced by 20 μM AlCl3 and upregulated by AlCl3 treatment for 2 h. In different tissues, the expression of GmWRKY81 was differentially induced. In 0–1 cm root tips, the expression of GmWRKY81 was induced to the highest level. The overexpression of GmWRKY81 in soybean resulted in higher relative root elongation, root weight, depth, root length, volume, number of root tips and peroxidase activity but lower root average diameter, malonaldehyde and H2O2 contents, indicating enhanced Al tolerance. Moreover, RNA-seq identified 205 upregulated and 108 downregulated genes in GmWRKY81 transgenic lines. Fifteen of these genes that were differentially expressed in both AlCl3-treated and GmWRKY81-overexpressing soybean had the W-box element, which can bind to the upstream-conserved WRKY domain. Overall, the combined functional analysis indicates that GmWRKY81 may improve soybean Al tolerance by regulating downstream genes participating in Al3+ transport, organic acid secretion and antioxidant reactions

Phosphorylation of p38 MAPK (P-p38) and ERK1/2 induced by dbcAMP (100 µM) and hCG (10 IU/ml) in human placental syncytiotrophoblasts.

<p>Upper panels of each bar graph are the representative blots. The bar graphs are the average data of three experiments. *P<0.05, **P<0.01,***P<0.001 versus 0 min.</p

(A) Effect of SB203580 (p38 MAPK inhibitor, 10 µM) on the basal and dbcAMP (100 µM) and hCG (10 IU/ml)-induced HSD11B2 protein level in human placental syncytiotrophoblasts.

<p>*p<0.05, **p<0.01, ***p<0.001 versus control; ## p<0.01 ### p<0.001 versus treatment with dbcAMP and hCG, n = 4. (B) Effect of SB203580 (p38 MAPK inhibitor, 10 µM) on the basal and dbcAMP, 100 µM) and hCG (10 IU/ml)-induced SP1 protein level in human placental syncytiotrophoblasts. ***p<0.001 vs control; ### p<0.001 versus treatment with dbcAMP and hCG (n = 4).</p

Primer sequences used for PCR.

<p>Primer sequences used for PCR.</p

(A) Effect of PD98059(ERK1/2 MAPK inhibitor, 50 µM) on the basal and dbcAMP (100 µM) and hCG (10 IU/ml)-induced HSD11B2 mRNA expression in human placental syncytiotrophoblasts.

<p>*p<0.05, **p<0.01, ***p<0.001 versus control (n = 4) (B) Effect of PD98059 (ERK1/2 MAPK inhibitor, 50 µM) on the basal and dbcAMP(100 µM) and hCG (10 IU/ml)-induced SP1 mRNA expression in human placental syncytiotrophoblasts. *p<0.05, **p<0.01, ***p<0.001 versus control (n = 4).</p

(A) Effect of SB203580 (p38 MAPK inhibitor, 10 µM) on the basal and dbcAMP (100 µM) and hCG (10 IU/ml)-induced HSD11B2 mRNA expression in human placental syncytiotrophoblasts.

<p>*p<0.05, **p<0.01, ***p<0.001 versus control; ## p<0.01 ### p<0.001 versus treatment with db-cAMP and hCG n = 4; (B) Effect of SB203580 (p38 MAPK inhibitor, 10 µM) on the basal and dbcAMP (db cAMP, 100 µM) and hCG (10 IU/ml)-induced SP1 mRNA expression in human placental syncytiotrophoblasts. *p<0.05, **p<0.01, ***p<0.001 versus control;# p<0.05, ## p<0.01 versus treatment with dbcAMP and hCG (n = 4).</p

Molecular Hydrogen Increases Quantitative and Qualitative Traits of Rice Grain in Field Trials

How to use environmentally friendly technology to enhance rice field and grain quality is a challenge for the scientific community. Here, we showed that the application of molecular hydrogen in the form of hydrogen nanobubble water could increase the length, width, and thickness of brown/rough rice and white rice, as well as 1000-grain weight, compared to the irrigation with ditch water. The above results were well matched with the transcriptional profiles of representative genes related to high yield, including up-regulation of heterotrimeric G protein β-subunit gene (RGB1) for cellular proliferation, Grain size 5 (GS5) for grain width, Small grain 1 (SMG1) for grain length and width, Grain weight 8 (GW8) for grain width and weight, and down-regulation of negatively correlated gene Grain size 3 (GS3) for grain length. Meanwhile, although total starch content in white rice is not altered by HNW, the content of amylose was decreased by 31.6%, which was parallel to the changes in the transcripts of the amylose metabolism genes. In particular, cadmium accumulation in white rice was significantly reduced, reaching 52% of the control group. This phenomenon was correlated well with the differential expression of transporter genes responsible for Cd entering plants, including down-regulated Natural resistance-associated macrophage protein (Nramp5), Heavy metal transporting ATPase (HMA2 and HMA3), and Iron-regulated transporters (IRT1), and for decreasing Cd accumulation in grain, including down-regulated Low cadmium (LCD). This study clearly showed that the application of molecular hydrogen might be used as an effective approach to increase field and grain quality of rice