Mixed Polyethylene Glycol-Modified Breviscapine-Loaded Solid Lipid Nanoparticles for Improved Brain Bioavailability: Preparation,Characterization, and In Vivo Cerebral Microdialysis Evaluation in Adult Sprague Dawley Rats

Breviscapine is used in the treatment of ischemic cerebrovascular diseases, but it has a low bioavailability in the brain due to its poor physicochemical properties and the activity of P-glycoprotein efflux pumps located at the blood–brain barrier. In the present study, breviscapine-loaded solid lipid nanoparticles (SLN) coated with polyethylene glycol (PEG) derivatives were formulated and evaluated for their ability to enhance brain bioavailability. The SLNs were either coated with polyethylene glycol (40) (PEG-40) stearate alone (Bre-GBSLN-PS) or a mixture of PEG-40 stearate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 (DSPE-PEG₂₀₀₀) (Bre-GBSLN-PS-DSPE) and were characterized both in vitro and in vivo. The mean particle size, polydispersity index, and entrapment efficiency for Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE were 21.60 ± 0.10 and 22.60 ± 0.70 nm, 0.27 ± 0.01 and 0.26 ± 0.04, and 46.89 ± 0.73% and 47.62 ± 1.86%, respectively. The brain pharmacokinetic parameters revealed that the brain bioavailability of breviscapine from the Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE was significantly enhanced (p < 0.01) with the area under concentration–time curve (AUC) of 1.59 ± 0.39 and 1.42 ± 0.58 μg h/mL of breviscapine, respectively, in comparison to 0.11 ± 0.02 μg h/mL from the commercial breviscapine injection. The ratios of the brain AUC for scutellarin in comparison with the plasma scutellarin AUC for commercial breviscapine injection, Bre-GBSLN-PS, and Bre-GBSLN-PS-DSPE were 0.66%, 2.82%, and 4.51%, respectively. These results showed that though both SLN formulations increased brain uptake of breviscapine, Bre-GBSLN-PS-DSPE which was coated with a binary combination of PEG-40 stearate and DSPE-PEG₂₀₀₀ had a better brain bioavailability than Bre-GBSLN-PS. Thus, the coating of SLNs with the appropriate PEG derivative combination could improve brain bioavailability of breviscapine and can be a promising tool for brain drug delivery.KEY WORDS: breviscapine, microdialysis, mixed PEGylation, P-glycoprotein (P-gp), solid lipid nanoparticles     

Cloning, expression and function of phosphate transporter encoded gene in Oryza sativa L.

OsPT6:1, a phosphate transporter encoding gene from the leaf samples of Oryza sativa, was identified through PCR with specifically designed primers. The phylogenetic analysis and the conserved amino acid residue site detection suggested OsPT6:1 a possible high-affinity phosphate transporter encoding gene. In situ hybridization and RT-PCR demonstrated the expression of OsPT6:1 in both roots and leaves. The peak expression signal was observed in mesophyll cells under low phosphorus (P) induction. A homologous recombination study indicated that OsPT6:1 can enhance the Pi uptake efficiency of Pichia pastoris. At the meantime, the introduction of OsPT6:1 was able to complement the Pi uptake function of yeast cells with high-affinity phosphate transporters deficient. Those results substantiated our contention that OsPT6:1 encoded a high-affinity phosphate transporter of Oryza sativa. These authors contributed equally to this work.     

Magnesium Deficiency Enhances Hydrogen Peroxide Production and Oxidative Damage in Chick Embryo Hepatocyte In Vitro

Magnesium deficiency and oxidative stress have been identified as correlative factors in many diseases. The origin of free radicals correlated with oxidative damage resulting from Mg-deficiency is unclear at the cellular level. To investigate whether hydrogen peroxide (H₂O₂) is associated in the oxidative stress induced by Mg-deficiency, the effect of Mg²⁺ deficiency (0, 0.4, 0.7 mM) on the metabolism of H₂O₂ was investigated in cultured chick embryo hepatocytes. After being cultured in the media with various concentrations of Mg²⁺ for 1, 2, 4, 6 and 10 days, parameters of H₂O₂ production, catalase activity, lipid peroxidation, intracellular total Mg and cell viability were analyzed. Results demonstrated that long-term incubation of chick embryo hepatocyte in extracellular Mg²⁺-deprivative and Mg²⁺-deficient (0.4 mM) states significantly enhanced the production of H₂O₂ (approximately twofold, respectively) and lipid peroxidation in the cell cultures, while decreasing the cell viability. Additionally, the reversing action of Mg²⁺ re-added to 1.0 mM and the partial reversing action of dimethylthiourea suggested that (i) [Mg²⁺]_e deficiency induced the increase of H₂O₂ production, (ii) [Mg²⁺]_e deficiency decreased catalase activity in chick embryo hepatocyte in vitro, subsequently causing oxidative stress and cell peroxidative damage.     

陕南晚震旦世Gaojiashania的保存特征及形态解释

陕西宁强地区灯影组高家山段地层中特异原地埋藏的管状化石Gaojiashania Yang et al.,1986为体似蚕状或带状,直或微弯,由密集圆环（或皱脊）彼此连接在一起形成的管状化石,对化石的埋藏及保存特征的研究表明,不同的矿化阶段形成不同的保存特征,早期黄铁矿化对化石保存起着重要作用。Gaojiashania以其特殊的圆环叠置的保存方式,与软躯体蠕形动物化石以及遗迹化石的保存迥然不同,推测Gaojiashania生物体已具有分节现象,在成分上也有差别,圆环部分可能具有一定的矿化,属于较为高等的生物门类。     

Tobacco Knowledge among Adults in Zhejiang Province,China

Objective

The aims of current study were to assess the level of tobacco knowledge, anti-tobacco messages and major information channels in Zhejiang.

Methods

Face-to-face interviews were conducted with 2112 adults in Zhejiang. Data on demographic information, smoking status, tobacco knowledge, anti-tobacco messages and major information channels was collected.

Results

The findings revealed that only 31.87% of the population were aware that smoking could cause all three diseases (stoke, heart disease, and lung cancer), 86.09% were aware that smoking causes lung cancer, 46.43% and 42.40% were aware that smoking causes stroke and heart attack, respectively. Residence and education level had significant effects on awareness, while the effects of smoking status, gender, age, and household monthly income were not significant. There were five major information channels as follows: television (67.52%), newspapers or magazines (40.79%), billboards (30.02%), public walls (24.72), and radio (23.79%). Respondents got the following anti-tobacco messages from mass media: “No smoking in public” (66.34%), “No smoking in front of other people” (35.18%) and “Not offering cigarettes to one another” (22.82%).

Conclusions

The tobacco knowledge among residents in Zhejiang province is relatively poor. Improved information channels and content of anti-tobacco messages are necessary to increase the public’s tobacco knowledge, particularly among rural residents and people with less education.     

Effects of sand burial depth on the root system of Salix cheilophila seedlings in Mu Us Sandy Land, Inner Mongolia, China

Salix cheilophila Schneid. is a naturally occurring Salix species in Mu Us Sandy Land, Inner Mongolia, China. We focused on the morphological adaptability of S. cheilophila to sand dune burial. For morphological measurements, 32 S. cheilophila seedlings were removed from a community which was in the process of being buried by a shifting sand dune. Each seedling collected included the entire root system. We measured the number, length, and biomass of the adventitious roots, primary lateral roots, and taproot, and compared the morphological characteristics of the root system, including adventitious roots, for seedlings buried to various levels in the sand. The growth range of adventitious roots increased as the length of the buried portion of the main shoot increased. In addition, the total dry weight of all current-year shoots tended to increase gradually with increasing total dry weight of the adventitious roots. These results suggest that S. cheilophila tends to make use of the sedimentary sand layer that accompanies shifting sand dunes. However, there was no correlation between biomass or number of adventitious roots and the length of the buried part of the main shoot. Thus, S. cheilophila does not grow adventitious roots proportional to the buried part. These morphological characteristics of the root system, including the adventitious roots, may indicate that S. cheilophila has poor morphological adaptability to sand dune burial.     

萎缩芽胞杆菌CKL1促盐胁迫下燕麦生长活性及其功能基因分析

【背景】青海省特殊生境孕育了特殊微生物资源。【目的】探究适合生活于高原生境的芽胞杆菌菌源。【方法】采用平板对峙法、显色法对萎缩芽胞杆菌（Bacillus atrophaeus） CKL1的拮抗、产吲哚乙酸活性进行测定,并检测耐低温、耐盐性及菌株对盐胁迫下燕麦品种（Avena sativa）“青燕1号”种子萌发、幼苗生长效应及叶绿素、脯氨酸、丙二醛的含量变化,利用二代测序技术对菌株进行基因组测序并分析相关功能基因。【结果】菌株CKL1对禾谷镰孢菌（Fusarium graminearum）、锐顶镰孢菌（Fusarium acuminatum）表现出显著的拮抗活性（抑菌圈直径>15 mm）;与Salkowski比色液反应变红,能在NaCl浓度为13%的LB培养基及4℃低温下生长,表现出一定的产吲哚乙酸、耐盐及耐低温活性;盐胁迫下,菌株CKL1对“青燕1号”种子萌发及幼苗生长具有显著促进作用,叶绿素及脯氨酸含量显著增加,丙二醛含量下降,增强了燕麦的抗盐性。菌株CKL1基因组全长为14 281 280 bp,与GO功能数据库比对注释到3 303个功能基因;基因组编码与脂肽类化合物itur...     

Development of a novel feeding regime for large scale production of human umbilical cord mesenchymal stem/stromal cells

Cytotechnology - Human umbilical cord mesenchymal stem/stromal cells (hUC-MSCs) have attracted significant research interests in regenerative medicine and cell-based therapies due to their...     

Optimization of covalent immobilization of pectinase on sodium alginate support

Pectinase was immobilized on a sodium alginate support using glutaraldehyde and retained 66% activity. The optimal pH for activity shifted from 3.0 to 3.5 after immobilization; however, the optimum temperature remained unchanged at 40°C. The immobilized enzyme also had a higher thermal stability and reusability than the free enzyme, and retained 80% of initial activity after 11 batch reactions.