Increased lipogenesis and stearate accelerate vascular calcification in calcifying vascular cells

Vascular calcification is recognized as an independent predictor of cardiovascular mortality, particularly in subjects with chronic kidney disease. However, the pathways by which dysregulation of lipid and mineral metabolism simultaneously occur in this particular population remain unclear. We have shown that activation of the farnesoid X receptor (FXR) blocks mineralization of bovine calcifying vascular cells (CVCs) and in ApoE knock-out mice with 5/6 nephrectomy. In contrast to FXR, this study showed that liver X receptor (LXR) activation by LXR agonists and adenovirus-mediated LXR overexpression by VP16-LXRα and VP16-LXRβ accelerated mineralization of CVCs. Conversely, LXR inhibition by dominant negative (DN) forms of LXRα and LXRβ reduced calcium content in CVCs. The regulation of mineralization by FXR and LXR agonists was highly correlated with changes in lipid accumulation, fatty acid synthesis, and the expression of sterol regulatory element binding protein-1 (SREBP-1). The rate of lipogenesis in CVCs through the SREBP-1c dependent pathway was reduced by FXR activation, but increased by LXR activation. SREBP-1c overexpression augmented mineralization in CVCs, whereas SREBP-1c DN inhibited alkaline phosphatase activity and mineralization induced by LXR agonists. LXR and SREBP-1c activations increased, whereas FXR activation decreased, saturated and monounsaturated fatty acids derived from lipogenesis. In addition, we found that stearate markedly promoted mineralization of CVCs as compared with other fatty acids. Furthermore, inhibition of either acetyl-CoA carboxylase or acyl-CoA synthetase reduced mineralization of CVCs, whereas inhibition of stearoyl-CoA desaturase induced mineralization. Therefore, a stearate metabolite derived from lipogenesis might be a risk factor for the development of vascular calcification.     

Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells

Using a flow cytometry-based screen of commercial antibodies, we have identified cell-surface markers for the separation of pancreatic cell types derived from human embryonic stem (hES) cells. We show enrichment of pancreatic endoderm cells using CD142 and of endocrine cells using CD200 and CD318. After transplantation into mice, enriched pancreatic endoderm cells give rise to all the pancreatic lineages, including functional insulin-producing cells, demonstrating that they are pancreatic progenitors. In contrast, implanted, enriched polyhormonal endocrine cells principally give rise to glucagon cells. These antibodies will aid investigations that use pancreatic cells generated from pluripotent stem cells to study diabetes and pancreas biology.     

Effect of different iron loads on serum and tissue biochemical parameters and liver hepcidin mRNA abundance of neonatal piglets

Iron (Fe) is an essential and important trace element for animals. In order to study its metabolism and relationship with hepcidin, piglet models of Fe-deficiency and Fe-overload were established by intramuscular injection with different doses of Fe-dextran (150 mg Fe/ml) within 1 week of age. Twelve piglets were divided into three groups of four animals: deficiency, regular and overload group, receiving 0 ml, 1 ml and 6 ml Fe-dextran, respectively. The piglets were euthanised at the age of 7 days for analysis. The results showed that the Fe-concentrations in liver, spleen and serum of piglets in the overload group were higher than in the regular and deficiency groups (p < 0.05). In the overload group, several serum biochemical parameters, e.g. globulin, total bilirubin, total cholesterol, high density lipoprotein (HDL), malondialdehyde, glutathione peroxidase (GPx), peroxidase and xanthine oxidase were higher, while alkaline phosphatase (AKP) and triglycerides were lower, compared with the regular group (p < 0.05). The serum concentrations of AKP, total bilirubin and peroxidase in the deficiency group were lower, while HDL and GPx were higher, compared with the regular group (p < 0.05). Hepcidin mRNA abundance was 131 times lower in the liver of piglets with Fe-deficiency, and 7 times higher in the overloaded group than that in the regular group (p < 0.05). In conclusion, Fe-overload and deficiency would influence Fe-metabolism, serum biochemical indexes, oxidation state and hepcidin mRNA abundance in piglet liver.     

广东车八岭自然保护区蕨类植物资源及其综合利用

据调查统计,车八岭国家级自然保护区共有蕨类植物38科80属195种。根据经济价值、应用和生长状况,将其划分为7类,分别是药用类、食用类、观赏类、工业用类、指示类和珍稀特有类;本文还就该保护区蕨类植物资源的现状与特点,提出合理的开发利用建议。     

Earliness index deters <Emphasis Type="Italic">Pectinophora gossypiella</Emphasis> incidence on advanced cultivars of <Emphasis Type="Italic">Bt</Emphasis> cotton

Pink bollworm (Pectinophora gossypiella) is recognized as an important pest of cotton and can damage flowers and bolls of both Bt and non-Bt cultivars. Cry-1Ac in Bt cultivars is considered very effective in controlling lepidopterous larvae; therefore, the present study was carried out to investigate the impact of Cry1-Ac and the earliness index on the natural incidence of P. gossypiella at the Cotton Research Institute, Faisalabad. During 2015–2016, ten cultivars were used to determine the incidence of pink bollworm infestation. The experiment was repeated for 2 years. During the next year, Cry1-Ac and earliness traits of selected cultivars were also observed to determine their impact on pink bollworm. Correlation coefficient results regarding days to first flower (r value = 0.66) as well as the earliness index (r value = ? 0.62) exhibited a strong association with pink bollworm, but Cry1-Ac had a weak association (r value = ? 0.058) with pink bollworm. The coefficient of determination (R ²) explained that variability of pink bollworm due to Cry1-Ac, the earliness index, and days to first flower was 18.0, 38.5, and 43.5%, respectively. Principal component analysis results showed that the first two PCs expressed 87% of the total variability. Clusters made on the basis of the studied parameters revealed that clusters 2 and 3 comprised the cotton cultivars possessing earliness traits compared with cluster 1. Therefore, it can be concluded that the earliness index in cotton is an important component for the sustainable management of pink bollworm infestation, the need for which is endless to evade the pink bollworm problem in the era of climate change.     

Angiopoietin-Like 4 Confers Resistance to Hypoxia/Serum Deprivation-Induced Apoptosis through PI3K/Akt and ERK1/2 Signaling Pathways in Mesenchymal Stem Cells

Angiopoietin-like 4 (ANGPTL4) is a potential anti-apoptotic agent for various cells. We examined the protective effect of ANGPTL4 on hypoxia/serum deprivation (SD)-induced apoptosis of MSCs, as well as the possible mechanisms. MSCs were obtained from rat bone marrow and cultured in vitro. Apoptosis was induced by hypoxia/SD for up to 24 hr, and assessed by flow cytometry and TUNEL assay. Expression levels of Akt, ERK1/2, focal adhesion kinase (FAK), Src, Bcl-2, Bax, cytochrome C and cleaved caspase-3 were detected by Western blotting. Integrin β1 mRNA was detected by qRT-PCR. Mitochondrial membrane potential was assayed using a membrane-permeable dye. Hypoxia/SD-induced apoptosis was significantly attenuated by recombinant rat ANGPTL4 in a concentration dependent manner. Moreover, ANGPTL4 decreased the hypoxia/SD-induced caspase-3 cleavage and the cytochrome C release, but increased the Bcl-2/Bax ratio and the mitochondrial membrane potential. Decreased expression of integrin β1, the ANGPTL4 receptor was observed during hypoxia/SD conditions, however, such decrease was reversed by ANGPTL4. In addition, ANGPTL4 induced integrin β1-associated FAK and Src phosphorylation, which was blocked by anti-integrin β1 antibody. ANGPTL4 also reversed the hypoxia/SD-induced decrease of Akt and ERK 1/2 phosphorylation, and the effect of ANGPTL4 was abolished by inhibitors of either integrins, ERK1/2, or phosphatidylinositol 3-kinase (PI3K). Blocking integrinβ1, Akt or ERK largely attenuated anti-apoptotic effect of ANGPTL4. ANGPTL4 protects MSCs from hypoxia/SD-induced apoptosis by interacting with integrins to stimulate FAK complex, leading to downstream ERK1/2 and PI3K/Akt signaling pathways and mimicking the pathway in which MSCs contact with the extracellular matrix.     

Radiation pressure on a biconcave human Red Blood Cell and the resulting deformation in a pair of parallel optical traps

We calculated the three‐dimensional optical stress distribution and the resulting deformation on a biconcave human red blood cell (RBC) in a pair of parallel optical trap. We assumed a Gaussian intensity distribution with a spherical wavefront for each trapping beam and calculated the optical stress from the momentum transfer associated with the reflection and refraction of the incident photons at each interface. The RBC was modelled as a biconcave thin elastic membrane with uniform elasticity and a uniform thickness of 0.25 μm. The resulting cell deformation was determined from the optical stress distribution by finite element software, Comsol Structure Mechanics Module, with Young's modulus (E) as a fitting parameter in order to fit the theoretical results for cell elongation to our experimental data. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Clinical significance of circulating microRNAs as diagnostic biomarkers for coronary artery disease

Coronary artery disease (CAD) is one of the biggest threats to human life. Circulating microRNAs (miRNAs) have been reported to be linked to the pathogenesis of CAD, indicating the possible role in CAD diagnosis. The present study aimed to explore the expression profile of plasma miRNAs and estimate their value in diagnosis for CAD. 67 Non‐CAD control subjects and 88 CAD patients were enrolled. We conducted careful evaluation by RT‐PCR analysis, Spearman rank correlation coefficients analysis, Receiver Operating Characteristic (ROC) curves analysis and so on. The plasma levels of six miRNAs known to be related to CAD were measured and three of them showed obvious expression change. Circulating miR‐29a‐3p, miR‐574‐3p and miR‐574‐5p were all significantly increased. ROC analysis revealed the probability of the three miRNAs as biomarkers with AUCs (areas under the ROC curve) of 0.830, 0.792 and 0.789, respectively. They were significantly correlated with each other in CAD patients, suggesting the possibility of joint diagnosis. The combined AUC was 0.915, much higher than each single miRNA. Therefore, our study revealed three promising biomarkers for early diagnosis of CAD. The combination of these miRNAs may act more effectively than individual ones for CAD diagnosis.