Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR

Background

Accumulating evidence reveals that intrauterine growth retardation (IUGR) can cause varying degrees of pulmonary arterial hypertension (PAH) later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR.

Methods

The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC) were isolated from the rat lungs by magnetic-activated cell sorting (MACS). We investigated epigenetic regulation of the endothelin-1 (ET-1) gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia.

Results

The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α) binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling.

Conclusions

These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.     

长江源区紫花针茅草原群落数量分类与排序

选择长江源地区典型的紫花针茅草原作为研究对象,以大量的群落学样方调查为基础,采用TWINS-PAN、DCA、物种多样性,相关分析等多元数量分析方法,系统研究了紫花针茅草原的群落特征、物种多样性、群落与环境因子的关系.结果表明：(1)所调查的紫花针茅草原是物种组成相对简单、菊科和禾本科植物最多、北温带分布属为主体的草原群落;(2)长江源区紫花针茅草原群落可划分为四个群丛类型：紫花针茅＋密丛棘豆群丛,紫花针茅＋梭罗草群丛,紫花针茅＋伊凡苔草群丛,紫花针茅＋弱小火绒草群丛;(3)影响群丛分布的主要环境因子首先是海拔、经纬度等空间因子,其次是湿润度、降雨量等水分因子的影响;(4)紫花针茅＋伊凡苔草群丛的物种多样性是研究区四个群丛中最高的.Simpson指数和均匀度指数受海拔、经纬度、平均降雨量、均湿润度等环境因子影响显著.该研究揭示了紫花针茅草原群落的内在规律.     

A novel tissue array technique for high-throughput tissue microarray analysis — microarray groups

Tissue microarrays are ordered arrays of hundreds to thousands of tissue cores in a single paraffin block. We invented a novel method to make a high-throughput microarray group. Conventional smaller tissue microarrays were made first and then sectioned. Separate paraffin films were arrayed orderly onto a regular-sized glass slide to form a larger microarray group. Sections were not floated in a water bath but, rather, were cut singly using conventional microtome, arrayed orderly onto the glass slide with forceps instead of using a tape-based tissue transfer system, and then unfolded with warm water (46° C) using a micropipette. This not only lowers the difficulty in sectioning but the overall tissue disks can be included in the same section. A microarray group of 2,534 small disks (theoretically, 2,560 disks can be made; 26 fell off during the procedure), the most up to now, was successfully made and may be used in immunohistochemistry, mRNA in situ hybridization, and flourescent in situ hybridization.     

山奈酚和槲皮素对大鼠体内Neu5Gc合成的影响及分子机制探究

非人源性唾液酸N-羟乙酰神经氨酸(N-glycolylneuraminic acid, Neu5Gc)是红肉中潜在的致癌性因子。唾液酸转移酶是涉及转运其前体物质的关键酶之一。大鼠用不同浓度的山奈酚(kaempferol,KA)和槲皮素(quercetin,Qu)灌胃,并模拟宰前对Neu5Gc合成影响的结果表明,不同浓度的KA、Qu对大鼠体内肌肉组织、肝和肾中Neu5Gc的含量均有一定的影响,最大抑制率分别为36.44%±0.11%和33.37%±0.08%。为探究其抑制机制,采用唾液酸转移酶(sialyltransferase,ST)与KA、Qu进行分子对接和分子动力学模拟分析。分子对接复合物二维相互作用图表明:KA和Qu能有效占据ST特异性抑制剂5′-胞苷单磷酸的活性位点氨基酸残基;对最佳复合物进行200 ns的动力学模拟结果显示,ST和KA产生稳定氢键作用的氨基酸残基主要是His301和Gly298,与Qu产生氢键作用的氨基酸残基主要是Gly293、Glu324、Thr272和Ser276。结合自由能分析表明,范德华力、静电吸引作用对抑制过程具有重要作用。本研究为合成和筛选高效ST抑制剂提供了一定实验依据。     

Influence of ambient temperature on maternal thermoregulation and neonate phenotypes in a viviparous lizard, Eremias multiocellata, during the gestation period

To assess the potential gestational effects on post-hatching morphology, locomotor performance, and early growth rate, we maintained gravid Eremias multiocellata under four constant treatment temperatures (25, 29, 31, and 35 °C). Ambient temperature had significant effects on some morphometric traits of offspring, including tail length, head size, forelimb length and hindlimb length, but not on body mass or snout-vent length. The data of females' body temperature indirectly support the maternal manipulation hypothesis. Juvenile E. multiocellata had better locomotor performance and faster early growth rate at 29 °C than at the other three treatment temperatures (25, 31, and 35 °C). Our results suggest that gestation temperature may be optimized at 29 °C for E. multiocellata from Tianzhu, Gansu Province, China.     

Asparanin A induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells

We recently established that asparanin A, a steroidal saponin extracted from Asparagus officinalis L., is an active cytotoxic component. The molecular mechanisms by which asparanin A exerts its cytotoxic activity are currently unknown. In this study, we show that asparanin A induces G₂/M phase arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Following treatment of HepG2 cells with asparanin A, cell cycle-related proteins such as cyclin A, Cdk1 and Cdk4 were down-regulated, while p21^WAF1/Cip1 and p-Cdk1 (Thr14/Tyr15) were up-regulated. Additionally, we observed poly (ADP-ribose) polymerase (PARP) cleavage and activation of caspase-3, caspase-8 and caspase-9. The expression ratio of Bax/Bcl-2 was increased in the treated cells, where Bax was also up-regulated. We also found that the expression of p53, a modulator of p21^WAF1/Cip1 and Bax, was not affected in asparanin A-treated cells. Collectively, our findings demonstrate that asparanin A induces cell cycle arrest and triggers apoptosis via a p53-independent manner in HepG2 cells. These data indicate that asparanin A shows promise as a preventive and/or therapeutic agent against human hepatoma.     

Melanoma cell expression of CD200 inhibits tumor formation and lung metastasis via inhibition of myeloid cell functions

CD200 is a cell surface glycoprotein that functions through engaging CD200 receptor on cells of the myeloid lineage and inhibits their functions. Expression of CD200 has been implicated in a variety of human cancer cells including melanoma cells and has been thought to play a protumor role. To investigate the role of cancer cell expression of CD200 in tumor formation and metastasis, we generated CD200-positive and CD200-negative B16 melanoma cells. Subcutaneous injection of CD200-positive B16 melanoma cells inhibited tumor formation and growth in C57BL/6 mice but not in Rag1^−/−C57BL/6 mice. However, i.v. injection of CD200-positive B16 melanoma cells dramatically inhibited tumor foci formation in the lungs of both C57BL/6 and Rag1^−/−C57BL6 mice. Flow cytometry analysis revealed higher expression of CD200R in Gr1⁺ myeloid cells in the lung than in peripheral myeloid cells. Depletion of Gr1⁺ cells or stimulation of CD200R with an agonistic antibody in vivo dramatically inhibited tumor foci formation in the lungs. In addition, treatment with tumor antigen specific CD4 or CD8 T cells or their combination yielded a survival advantage for CD200 positive tumor bearing mice over mice bearing CD200-negative tumors. Taken together, we have revealed a novel role for CD200-CD200R interaction in inhibiting tumor formation and metastasis. Targeting CD200R may represent a novel approach for cancer immunotherapy.     

Involvement of microglia activation in the lead induced long-term potentiation impairment

Exposure of Lead (Pb), a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP) as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks) caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits.     

间套作提高农田水分利用效率的节水机理

综合国内外多学科的研究成果,从地表水向土壤水的转化效率、农田水分的有效性、植物冠层结构、灌溉用水量和作物产量等方面,论述了间套作提高农田水分利用效率的节水机理.结果表明:间套作能够促进植物根系对农田水分的充分利用,有利于增加根层土壤的贮水量;间套作一方面减小棵间蒸发、抑制无效蒸腾,另一方面优化作物系统的源-库关系,创造出有利于植物生长发育的小气候,为资源在时间和空间上的集约利用和高产打好基础,在不增加农田灌溉水的同时大幅度提高单位面积产量,促进作物水分利用效率明显提高.