Angiotoxic effects of chlorinated polyfluorinated ether sulfonate, a novel perfluorooctane sulfonate substitute, in vivo and in vitro.

Chlorinated polyfluorinated ether sulfonate (Cl-PFESA), a substitute for perfluorooctane sulfonate (PFOS), has been widely used in the Chinese electroplating industry under the trade name F-53B. The production and use of F-53B is keep increasing in recent years, consequently causing more emissions into the environment. Thus, there is a growing concern about the adverse effects of F-53B on human health. However, related research is very limited, particularly in terms of its toxicity to the vascular system. In this study, C57BL/6 J mice were exposed to 0.04, 0.2, and 1 mg/kg F-53B for 12 weeks to assess its impact on the vascular system. We found that F-53B exposure caused aortic wall thickening, collagen deposition, and reduced elasticity in mice. In addition, F-53B exposure led to a loss of vascular endothelial integrity and a vascular inflammatory response. Intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were found to be indispensable for this process. Furthermore, RNA sequencing analysis revealed that F-53B can decrease the repair capacity of endothelial cells by inhibiting their proliferation and migration. Collectively, our findings demonstrate that F-53B exposure induces vascular inflammation and loss of endothelial integrity as well as suppresses the repair capacity of endothelial cells, which ultimately results in vascular injury, highlighting the need for a more thorough risk assessment of F-53B to human health.

Kinase Inhibitor VvBKI1 Interacts with Ascorbate Peroxidase VvAPX1 Promoting Plant Resistance to Oomycetes.

Downy mildew caused by oomycete pathogen Plasmopara viticola is a devastating disease of grapevine. P. viticola secretes an array of RXLR effectors to enhance virulence. One of these effectors, PvRXLR131, has been reported to interact with grape (Vitis vinifera) BRI1 kinase inhibitor (VvBKI1). BKI1 is conserved in Nicotiana benthamiana and Arabidopsis thaliana. However, the role of VvBKI1 in plant immunity is unknown. Here, we found transient expression of VvBKI1 in grapevine and N. benthamiana increased its resistance to P. viticola and Phytophthora capsici, respectively. Furthermore, ectopic expression of VvBKI1 in Arabidopsis can increase its resistance to downy mildew caused by Hyaloperonospora arabidopsidis. Further experiments revealed that VvBKI1 interacts with a cytoplasmic ascorbate peroxidase, VvAPX1, an ROS-scavenging protein. Transient expression of VvAPX1 in grape and N. benthamiana promoted its resistance against P. viticola, and P. capsici. Moreover, VvAPX1 transgenic Arabidopsis is more resistant to H. arabidopsidis. Furthermore, both VvBKI1 and VvAPX1 transgenic Arabidopsis showed an elevated ascorbate peroxidase activity and enhanced disease resistance. In summary, our findings suggest a positive correlation between APX activity and resistance to oomycetes and that this regulatory network is conserved in V. vinifera, N. benthamiana, and A. thaliana.

Identification of potential long non-coding RNA biomarkers associated with the progression of colon cancer.

Increasing evidence has suggested that dysregulated lncRNA expression played important roles in the development and progression of human cancers. Although prognostic roles of lncRNAs have been recognized for colon cancer (CC) patients, the search for novel lncRNA biomarkers potentially involved in CC progression is an urgent and still largely unmet medical need. In this study, we evaluated the lncRNA expression changes during the progression of CC by analyzing two cohorts of previously published expression profiles of CC patients and identified hundreds of differentially expressed lncRNAs. Then we identified eight lncRNAs that closely associated with the progression of CC patients from a large number of significantly altered lncRNAs using random forest supervised classification algorithm. Finally, an SVM-based lncRNA risk classifier was developed to discriminate high-risk CC patients from persons with early-stage and validated in both the training dataset and testing dataset by survival analysis and five-fold cross-validation strategy. Our pathway enrichment analysis based on protein-coding genes that are co-expressed with lncRNAs, suggested that variation in expression of eight lncRNAs biomarkers might affect critical pathways involved in CC progression. With further validation, these eight lncRNAs might have significant implications for the clinical management of CC patients with early stage and improve our understanding of cancer progression.

Protective effects of seahorse extracts in a rat castration and testosterone-induced benign prostatic hyperplasia model and mouse oligospermatism model.

This study investigated the effects of seahorse (Hippocampus spp.) extracts in a rat model of benign prostatic hyperplasia (BPH) and mouse model of oligospermatism. Compared to the sham operated group, castration and testosterone induced BPH, indicated by increased penile erection latency; decreased penis nitric oxide synthase (NOS) activity; reduced serum acid phosphatase (ACP) activity; increased prostate index; and epithelial thickening, increased glandular perimeter, increased proliferating cell nuclear antigen (PCNA) index and upregulation of basic fibroblast growth factor (bFGF) in the prostate. Seahorse extracts significantly ameliorated the histopathological changes associated with BPH, reduced the latency of penile erection and increased penile NOS activity. Administration of seahorse extracts also reversed epididymal sperm viability and motility in mice treated with cyclophosphamide (CP). Seahorse extracts have potential as a candidate marine drug for treating BPH without inducing the side effects of erectile dysfunction (ED) or oligospermatism associated with the BPH drug finasteride.

Silencing of integrin-linked kinase suppresses in vivo tumorigenesis of human ovarian carcinoma cells.

Integrin-linked kinase (ILK) plays a role in the regulation of multiple cellular functions (e.g., promoting cell migration and proliferation, but inhibiting cell adhesion). This study investigated the inhibitory effects of ILK gene knockdown on the regulation of in vivo tumorigenesis of human ovarian carcinoma cells in nude mouse xenografts. HO-8910 cells were transfected with an ILK antisense oligonucleotide (ILK-ASO) to silence the ILK gene. Expression of ILK mRNA and protein was evaluated by RT-PCR and western blotting, respectively. The cell cycle was assessed by flow cytometric analysis. Cells with or without ILK-ASO transfection were subcutaneously injected into nude mice. The mouse body weight, tumor formation, tumor size and tumor weight were determined up to 30 days after inoculation. Tumor cells transfected with ILK-ASO had significantly decreased ILK mRNA and protein expression (P<0.01) when compared to the control cells. ILK gene silencing significantly increased the number of cells in the G0/G1 phase (67.61 vs. 43.29%, χ2=1197.15, P<0.01). After tumor cell inoculation, tumor cells transfected with ILK-ASO showed significantly delayed tumor formation when compared to control (9.10±0.74 vs. 5.30±0.67 days, respectively; P<0.01). In addition, tumor growth was suppressed in the 30 days following inoculation (P<0.01 compared with the controls). The average tumor weight in the ILK-ASO group was statistically lower than that of the control group (1.29±0.11 vs. 1.57±0.13 g, respectively; P<0.01). This study demonstrated that ILK-ASO transfection efficiently downregulated ILK expression in human ovarian carcinoma HO-8910 cells and that ILK gene silencing suppressed tumor growth in nude mice xenografts.

Effect of genotype, environment, and their interaction on phytochemical compositions and antioxidant properties of soft winter wheat flour.

The effect of genotype (G), growing environment (E), and their interaction (G×E) on the antioxidant properties and chemical compositions were investigated using the flour samples of 10 wheat varieties grown in four different locations in Maryland. Lutein content of wheat flour ranged from 0.10 to 0.69 µg/g, and α-tocopherol ranged from 0.12 to 0.83 µg/g. Total carotenoids were primarily affected by E (45.7%), while G×E interaction had a larger effect on the level of total tocopherols (71.6%). E had the largest effect on antioxidant activity against oxygen, hydroxyl, and ABTS(·+) radicals. G had the least influence on the measured phytochemicals and antioxidant activity assays. Total carotenoids had a significant correlation with average low air temperature (r=0.359, p<0.01) as well as precipitation level (r=0.214, p<0.01). ABTS(·+) radical scavenging capacity had a positive correlation with average air temperature (r=0.705, p<0.01), while hydroxyl radical scavenging capacity had a negative correlation with temperature (r=-0.269. p<0.01). These results show that environment, genotype, and their interaction could influence the levels of lipophilic antioxidants and antioxidant activities of wheat flour.

Phytochemical compositions, and antioxidant properties, and antiproliferative activities of wheat flour.

Ten soft wheat varieties grown in Maryland were compared for their phytochemical compositions, antioxidant properties and antiproliferative activities. Free radical scavenging capacities were examined against DPPH(·), oxygen, hydroxyl and ABTS(·+) radicals. Significant radical scavenging capacities were detected in all wheat flour extracts. Total phenolic content ranged from 1.66 to 2.01 mg of GAE/g wheat flour. The wheat flours contained 172.91-297.55 µg/g insoluble bound ferulic acid, contributing 89.74-94.29% of total ferulic acid on a per weight basis. The concentrations of lutein and zeaxanthin were 0.27-0.46 and 0.08-0.13 µg/g, respectively. In addition, the wheat flours had 0.30-0.59 and 0.07-0.29 µg/g α- and δ-tocopherols, respectively. Four wheat flour extracts were further examined for their antiproliferative activities. The Jamestown wheat flour showed significant antiproliferative activity against both HT-29 and Caco-2 colon cancer cells at the initial treatment concentration of 50 mg flour equivalents/ml, while USG3555 flour showed inhibitive effect only in HT-29 cancer cells, suggesting the different and possible selective antiproliferative property of the wheat flours. These results may be used to direct the breeding effects to produce soft winter wheat varieties with improved health properties.

Isoflavone composition and antioxidant capacity of modified-lipoxygenase soybeans grown in Maryland.

Maryland-grown soybean lines modified for low lipoxygenase-1 (LOX-1) content and a traditional nonmodified cultivar were analyzed for fatty acid composition, total phenolic content (TPC), isoflavone composition, relative DPPH• scavenging capacity (RDSC), and hydroxyl radical scavenging capacity (HOSC). Soybean lines included black, brown, and yellow soybeans. TPC of all soybean lines ranged from 2.84 to 4.74 mg gallic acid equiv (GAE)/g flour. Total isoflavones were between 2.78 and 8.66 µmol/g flour. RDSC of all lines was between 0.48 and 14.62 µmol Trolox equiv (TE)/g flour, and HOSC ranged from 53.57 to 135.52 µmol TE/g flour. Some modified-LOX genotypes demonstrated antioxidant capacity and/or isoflavone content similar to or higher than those of the nonmodified cultivar (P < 0.05). Black soybeans demonstrated higher TPC and RDSC than most yellow soybean lines, although they did not have higher isoflavone content. The results demonstrate that modification of the LOX trait did not necessarily alter the antioxidant capacity or chemical composition of the experimental soybean lines when compared with a nonmodified cultivar. These soybean lines may be studied further for nutraceutical properties and use in functional foods.