Protective effects of activated vitamin D receptor on radiation‐induced intestinal injury

Radiation‐induced intestinal injury (RIII) is a common complication after radiation therapy in patients with pelvic, abdominal, or retroperitoneal tumours. Recently, in the model of DSS (Dextran Sulfate Sodium Salt) ‐induced intestinal inflammatory injury, it has been found in the study that transgenic mice expressing hVDR in IEC (Intestinal Epithelial Cell) manifest highly anti‐injury properties in colitis, suggesting that activated VDR in the epithelial cells of intestine may inhibit colitis by protecting the mucosal epithelial barrier. In this study, we investigated the effect of the expression and regulation of VDR on the protection of RIII, and the radiosensitivity in vitro experiments, and explored the initial mechanism of VDR in regulating radiosensitivity of IEC. As a result, we found that the expression of VDR in intestinal tissues and cells in mice can be induced by ionizing radiation. VDR agonists are able to prolong the average survival time of mice after radiation and reduce the radiation‐induced intestinal injury. For lack of vitamin D, the radiosensitivity of intestinal epithelial cells in mice increased, which can be reduced by VDR activation. Ensuing VDR activation, the radiation‐induced intestinal stem cells damage is decreased, and the regeneration and differentiation of intestinal stem cells is promoted as well. Finally, on the basis of sequencing analysis, we validated and found that VDR may target the HIF/PDK1 pathway to mitigate RIII. We concluded that agonism or upregulation of VDR expression attenuates radiation‐induced intestinal damage in mice and promotes the repair of epithelial damage in intestinal stem cells.     

Effects of a moderate-intensity static magnetic field and adriamycin on K562 cells

The aim of this study was to investigate whether a moderate‐intensity static magnetic field (SMF) can enhance the killing effect of adriamycin (ADM) on K562 cells, and to explore the effects of SMF combined with ADM on K562 cells. We analyzed the metabolic activity of cells, cell cycle distribution, DNA damage, change in cell ultrastructure, and P‐glycoprotein (P‐gp) expression after K562 cells were exposed continuously to a uniform 8.8 mT SMF for 12 h, with or without ADM. Our results showed that the SMF combined with ADM (25 ng/ml) significantly inhibited the metabolic activity of K562 cells (P < 0.05), while neither ADM nor the SMF alone affected the metabolic activity of these cells. Cell ultrastructure was altered in the SMF + ADM group. For example, cell membrane was depressed, some protuberances were observable, and vacuoles in the cytoplasm became larger. Cells were arrested at the G2/M phase and DNA damage increased after cells were treated with the SMF plus ADM. ADM also induced the P‐gp expression. In contrast, in the SMF group and SMF + ADM group, the P‐gp expression was decreased compared with the ADM group. Taken together, our results showed that the 8.8 mT SMF enhanced the cytotoxity potency of ADM on K562 cells, and the decrease in P‐gp expression may be one reason underlying this effect. Bioelectromagnetics 32:191–199, 2011. © 2010 Wiley‐Liss, Inc.     

Synthesis of 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as platelet aggregation inhibitors

Novel 2H-benzo[b][1,4]oxazin-3(4H)-ones have been synthesized by condensation, reduction, O-alkylation and Smiles rearrangement using 3-bromo-4-hydroxy benzaldehyde, anilines, and chloroacetyl chloride as starting materials. All the synthesized compounds have been characterized by (1)H NMR, (13)C NMR, and HRMS, and tested for the inhibitory ability on platelet aggregation. The results have shown that the ADP (adenosine 5'-diphosphate)-induced platelet aggregation was inhibited by 7a-g with the IC(50) value at 10.14-18.83 μmol/L. Compound 7a exhibited the most potent inhibitory effect (IC(50)=10.14 μmol/L) among all the compounds, but less potent than the control drug ticlopidine (3.18 μmol/L) and aspirin (6.07 μmol/L). The preliminary structure-activity relationship (SAR) was initially investigated in the study.     

Genetic Variants in Meiotic Program Initiation Pathway Genes Are Associated with Spermatogenic Impairment in a Han Chinese Population

Background

The meiotic program initiation pathway genes (CYP26B1, NANOS1 and STRA8) have been proposed to play key roles in spermatogenesis.

Objective

To elucidate the exact role of the genetic variants of the meiosis initiation genes in spermatogenesis, we genotyped the potential functional genetic variants of CYP26B1, NANOS1 and STRA8 genes, and evaluated their effects on spermatogenesis in our study population.

Design, Setting, and Participants

In this study, all subjects were volunteers from the affiliated hospitals of Nanjing Medical University between March 2004 and July 2009 (NJMU Infertile Study). Total 719 idiopathic infertile cases were recruited and divided into three groups according to WHO semen parameters: 201 azoospermia patients (no sperm in the ejaculate even after centrifugation), 155 oligozoospermia patients (sperm counts <20×10⁶/ml) and 363 infertility/normozoospermia subjects (sperm counts >20×10⁶/ml). The control group consisted of 383 subjects with normal semen parameters, all of which had fathered at least one child without assisted reproductive technologies.

Measurements

Eight single nucleotide polymorphisms (SNPs) in CYP26B1, NANOS1 and STRA8 genes were determined by TaqMan allelic discrimination assay in 719 idiopathic infertile men and 383 healthy controls.

Results and Limitations

The genetic variant rs10269148 of STRA8 gene showed higher risk of spermatogenic impairment in the groups of abnormospermia (including azoospermia subgroup and oligozoospermia subgroup) and azoospermia than the controls with odds ratios and 95% confidence intervals of 2.52 (1.29–4.94) and 2.92 (1.41–6.06), respectively (P = 0.006, 0.002 respective). Notably, larger sample size studies and in vivo or in vitro functional studies are needed to substantiate the biological roles of these variants.

Conclusions

Our results provided epidemiological evidence supporting the involvement of genetic polymorphisms of the meiotic program initiation genes in modifying the risk of azoospermia and oligozoospermia in a Han-Chinese population.     

视觉和嗅觉信号对果蝇食物搜寻行为的协同作用

为了探索视觉和嗅觉信号在昆虫食物搜寻过程中的作用, 本研究利用杨梅和橘子为引诱物, 在实验室条件下测定了嗅觉和视觉信号诱集到的黑腹果蝇Drosophila melanogaster数量, 分析了嗅觉经历对果蝇嗅觉和视觉食物搜寻的影响。发现同源性嗅觉和视觉信号存在的杨梅诱集到的果蝇数量显著大于单一的视觉信号和嗅觉信号, 但异源性嗅觉和视觉信号组合诱集到的果蝇数量和单独的嗅觉信号相似。嗅觉信号预处理不仅能够显著增加嗅觉信号诱集到的果蝇数量, 其中杨梅嗅觉信号对杨梅预处理果蝇的吸引能力与视觉和嗅觉信号存在的杨梅相似, 而且异源性嗅觉和视觉信号组合诱集到的预处理果蝇数量也不低于视觉和嗅觉信号存在的杨梅。另外杨梅嗅觉信号预处理也能够显著增强杨梅视觉信号诱集到的果蝇数量。但嗅觉预处理并不会改变同源性视觉和嗅觉信号组合诱集到的果蝇数量。本研究表明, 果蝇同时利用视觉和嗅觉信号进行食物搜寻, 因此同源性视觉和嗅觉信号在果蝇诱集过程中具有协同作用。另外果蝇具有较强的记忆和学习能力, 能够将记忆中的嗅觉信号应用于食物搜寻。本研究结果不仅有利于我们了解果蝇在自然状态下的食物搜寻机制, 而且有利于开发更有效的果蝇新型诱捕器。     

军医大学学员坚毅性评价的内隐效应及脑电特征研究

目的:探寻军医大学学员内隐层面对自我和他人坚毅性评价的特点及脑电特征,为全面、客观的评估个体的坚毅性提供理论依据和客观指标。方法:使用E-Prime2.0参照经典内隐联想范式编制内隐联想-坚毅测验,对100名军医大学学员施测坚毅量表(Grit O),选取高、低坚毅水平被试(各20名)进行内隐联想-坚毅测验,并记录脑电,分析两组被试的内隐效应及主要脑电成分。结果:计算内隐效应D值,t检验显示高坚毅组(0.55±0.36)显著低于低坚毅组(0.87±0.49),t=-2.257,P0.05,Cohen'd=0.74。两组被试均诱发明显的N400和LPP,高坚毅组中N400在任务状态下主效应显著,F(1,17)=8.528,P0.05,η2=0.334,且在电极位置上主效应显著,F(10,170)=8.207,P0.001,η2=0.326。LPP在任务状态下主效应显著,F(1,17)=5.471,P0.05,η2=0.243,且在电极位置上主效应显著,F(10,170)=18.479,P0.001,η2=0.521;低坚毅组中N400在任务状态下主效应显著,F(1,17)=10.051,P0.05,η2=0.372,且在电极位置上主效应显著,F(10,170)=8.223,P0.001,η2=0.326,LPP在任务状态下主效应不显著。结论:1.军医大学学员坚毅性评价的内隐效应显著,即均倾向于认为自我的坚毅性高,他人的坚毅性低,通过问卷法评估坚毅性时应考虑坚毅评价的内隐效应。2.高、低坚毅性军医大学学员坚毅性内隐评价时的主要脑电成分N400、LPP存在差异,N400可作为坚毅性内隐评价符合程度的判断指标。3.内隐效应及N400可以作为对军医大学学员坚毅性评价时的客观指标。     

A Water‐Soluble Cu Complex as Molecular Catalyst for Electrocatalytic CO2 Reduction on Graphene‐Based Electrodes

A structurally simple molecular 1,10‐phenanthroline‐Cu complex on a mesostructured graphene matrix that can be active and selective toward CO₂ reduction over H₂ evolution in an aqueous solution is reported. The active sites consist of Cu(I) center in a distorted trigonal bipyramidal geometry, which enables the adsorption of CO₂ with η¹‐COO‐like configuration to commence the catalysis, with a turnover frequency of ≈45 s^?1 at ?1 V versus reversible hydrogen electrode. Using in situ infrared spectroelectrochemical investigation, it is demonstrated that the Cu complex can be reversibly heterogenized near the graphene surface via potential control. An increase of electron density in the complex is observed as a result of the interaction from the electric field, which further tunes the electron distribution in the neighboring CO₂. It is also found that the mesostructure of graphene matrix favored CO₂ reduction on the Cu center over hydrogen evolution by limiting mass transport from the bulk solution to the electrode surface.     

The role of dendritic cells regulated by HMGB1/TLR4 signalling pathway in myocardial ischaemia reperfusion injury

Inflammatory response plays an important role in ischaemia reperfusion injury (IRI) through a variety of inflammatory cells. Apart from neutrophils, macrophages and lymphocytes, the role of dendritic cells (DCs) in IRI has been noticed. The study was aimed at investigating whether the high‐mobility group protein box‐1/toll like receptor 4 (HMGB1/TLR4) signalling pathway regulate the migration, adhesion and aggregation of DCs to the myocardium, induce DCs activation and maturation, stimulate the expression of surface costimulatory molecules and participate in myocardial IRI. In vivo, migration, adhesion, and aggregation of DCs was enhanced; the expression of peripheral blood DCs CD80 and CD86, myocardial adhesion molecules were increased; and the infarct size was increased during myocardial ischaemia reperfusion injury myocardial ischemic/reperfusion injury (MI/RI). These responses induced by MI/RI were significantly inhibited by HMGB1 specific neutralizing antibody treatment. Cellular experiments confirmed that HMGB1 promoted the release of inflammatory cytokines through TLR4/MyD88/NF‐κB, upregulated CD80 and CD86 expression, mediated the damage of cardiomyocytes and accelerated the apoptosis. Our results indicate that DCs activation and maturation, stimulate the expression of surface costimulatory molecules by promoting the release of inflammatory factors through NF‐κB pathway and participate in myocardial IRI.