Herpes simplex viruses and induction of interferon responses

Herpes simplex viruses (HSV) are human pathogens responsible for a variety of diseases,including localized mucocutaneous lesions,encephalitis,and disseminated diseases.HSV infection leads to rapid induction of innate immune responses.A critical part of this host response is the type I IFN system including the induction of type I IFNs,IFN-mediated signaling and amplification of IFN response.This provides the host with immediate countermeasure during acute infection to limit initial viral replication and to facilitate an appropriate adaptive immune response.However,HSV has devised multiple strategies to evade and interfere with innate immunity.This review will focus on the induction of type I IFN response by HSV during acute infection and current knowledge of mechanisms by which HSV interferes with this induction process.     

Dissecting of the FHB resistance QTL on the short arm of wheat chromosome 2D using a comparative genomic approach: from QTL to candidate gene

Colinearity in gene content and order between rice and closely related cereal crops has been a powerful tool for gene identification. Using a comparative genomic approach, we have identified the rice genomic region syntenous to the region of the short arm of wheat chromosome 2D, on which quantitative trait loci (QTLs) for Fusarium head blight (FHB) resistance and for controlling accumulation of the mycotoxin deoxynivalenol (DON) are closely located. Utilizing markers known to reside near the FHB resistance QTL and data from several wheat genetic maps, we have limited the syntenous region to 6.8 Mb of the short arm of rice chromosome 4. From the 6.8-Mb sequence of rice chromosome 4, we found three putative rice genes that could have a role in detoxification of mycotoxins. DNA sequences of these putative rice genes were used in BLAST searches to identify wheat expressed sequence tags (ESTs) exhibiting significant similarity. Combined data from expression analysis and gene mapping of wheat homologues and results of analysis of DON accumulation using doubled haploid populations revealed that a putative gene for multidrug resistance-associated protein (MRP) is a possible candidate for the FHB resistance and/or DON accumulation controlling QTLs on wheat chromosome 2DS and can be used as a molecular marker to eliminate the susceptible allele when the Chinese wheat variety Sumai 3 is used as a resistance source. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Exosomes derived from siRNA against GRP78 modified bone-marrow-derived mesenchymal stem cells suppress Sorafenib resistance in hepatocellular carcinoma

Background

Sorafenib is an effective clinical drug in therapy of hepatocellular carcinoma, having led to improved prognosis in hepatocellular carcinoma patients. However acquired resistance is still being encountered. So, it is urgently to develop alternative strategies to overcome drug resistance. Exosomes can be modified with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. The GRP78 is overexpressed in Sorafenib resistant cancer cells compared to Sorafenib sensitive cancer cells and thus is able to act as a target for therapy of hepatocellular carcinoma.

Results

In this study, we modified BM-MSCs to express the exosomal siGRP78. And we show that siGRP78 modified exosomes combined with Sorafenib is able to target GRP78 in hepatocellular carcinoma cells and inhibit the growth and invasion of the cancer cells in vitro. Further, siGRP78 modified exosomes combined with Sorafenib also inhibit the growth and metastasis of the cancer cells in vivo.

Conclusions

siGRP78 modified exosomes could sensitize Sorafenib resistant cancer cells to Sorafenib and reverse the drug resistance.

     

Protective Role of p70S6K in Intestinal Ischemia/Reperfusion Injury in Mice

The mTOR signaling pathway plays a crucial role in the regulation of cell growth, proliferation, survival and in directing immune responses. As the intestinal epithelium displays rapid cell growth and differentiation and is an important immune regulatory organ, we hypothesized that mTOR may play an important role in the protection against intestinal ischemia reperfusion (I/R)-induced injury. To better understand the molecular mechanisms by which the mTOR pathway is altered by intestinal I/R, p70S6K, the major effector of the mTOR pathway, was investigated along with the effects of rapamycin, a specific inhibitor of mTOR and an immunosuppressant agent used clinically in transplant patients. In vitro experiments using an intestinal epithelial cell line and hypoxia/reoxygenation demonstrated that overexpression of p70S6K promoted cell growth and migration, and decreased cell apoptosis. Inhibition of p70S6K by rapamycin reversed these protective effects. In a mouse model of gut I/R, an increase of p70S6K activity was found by 5 min and remained elevated after 6 h of reperfusion. Inhibition of p70S6K by rapamycin worsened gut injury, promoted inflammation, and enhanced intestinal permeability. Importantly, rapamycin treated animals had a significantly increased mortality. These novel results demonstrate a key role of p70S6K in protection against I/R injury in the intestine and suggest a potential danger in using mTOR inhibitors in patients at risk for gut hypoperfusion.     

The Interaction Mode of Groove Binding Between Quercetin and Calf Thymus DNA Based on Spectrometry and Simulation

Quercetin, a ubiquitous flavanoid, has numerous pharmacological effects, such as antioxidant and antitumor. Previous studies showed nucleic acids were the potential biological targets for antitumor medicine. For exploring the mechanism of DNA‐target medicine, the interaction between quercetin and calf thymus DNA was studied based on the method of spectrometry and simulation in our study. Firstly, the interaction between quercetin and calf thymus DNA was confirmed by fluorescence spectrometry. Furthermore, circular dichroism, fluorescence polarization, competitive displacement assay, and salt concentration dependence assay were applied to search the interaction mode of quercetin‐calf thymus DNA, which proved the existence of groove binding and electrostatic interaction. Meanwhile, quenching constant K_sv, binding constant K_a and the number of binding sites n was calculated, inferring that the fluorescence quenching occurred by static quenching process, and the main acting force was hydrogen bond. Finally, molecular docking was used to simulate and analyze the interaction between quercetin and calf thymus DNA.     

Whole cell biocatalyst for biodiesel fuel production utilizing Rhizopus oryzae cells immobilized within biomass support particles

As part of a research program aimed at producing biodiesel fuel from plant oils enzymatically cells of Rhizopus oryzae (R. oryzae) IFO4697 (with a 1,3-positional specificity lipase) immobilized within biomass support particles (BSPs) were investigated for the methanolysis of soybean oil. The R. oryzae cells easily became immobilized within the BSPs during batch operation. To enhance the methanolysis activity of the immobilized cells under the culture conditions used, various substrate-related compounds were added to the culture medium. Among the compounds tested, olive oil or oleic acid was significantly effective. In contrast, no glucose was necessary. Immobilized cells were treated with several organic solvents, but none gave higher activity than untreated cells. When methanolysis was carried out with stepwise additions of methanol using BSP-immobilized cells, in the presence of 15% water the methyl esters (MEs) content in the reaction mixture reached 90% - the same level as that using the extracellular lipase. The process presented here, using a whole cell biocatalyst, is considered to be promising for biodiesel fuel production in industrial applications.     

河南黄河中游湿地维管植物与哺乳动物物种组成和分布特征

河南黄河湿地位于黄河中下游,由西向东随地势变化,动植物物种组成及多样性变化复杂。于2011年至2015年对三门峡市、洛阳市以及焦作市的黄河湿地保护区维管植物和哺乳动物进行了全面调查,比较分析了三个区域间动植物多样性的差异,采用非趋势对应分析和聚类分析对物种组成数据进行排序和分类,结果显示：（1）三门峡、洛阳和焦作黄河湿地维管植物分别有130科、493属、1128种及变种,128科、470属、1049种及变种,90科、290属、542种及变种;三门峡黄河湿地哺乳动物有6目、15科、48种,洛阳黄河湿地哺乳动物有7目、18科、61种,焦作黄河湿地哺乳动物有6目、11科、34种;（2）从三门峡黄河湿地经洛阳黄河湿地再到焦作黄河湿地,维管植物多样性降低;（3）三门峡黄河湿地维管植物多样性和哺乳动物多样性与洛阳黄河湿地差异不显著,与焦作黄河湿地差异显著。研究结果丰富了河南黄河湿地保护区植物和动物多样性研究资料,同时也为保护区的保护管理和科研监测提供参考。     

Design,synthesis, and evaluation of novel O-alkyl ferulamide derivatives as multifunctional ligands for treating Alzheimer’s disease

Herein, a series of novel O-alkyl ferulamide derivatives were designed and synthesised through the multi-target-directed ligands (MTDLs) strategy. The biological activities in vitro showed that compounds 5a, 5d, 5e, 5f, and 5h indicated significantly selective MAO-B inhibitory potency (IC₅₀ = 0.32, 0.56, 0.54, 0.73, and 0.86 μM, respectively) and moderate antioxidant activity. Moreover, compounds 5a, 5d, 5e, 5f, and 5h showed potent anti-inflammatory properties, remarkable effects on self-induced Aβ_1-42 aggregation, and potent neuroprotective effect on Aβ_1-42-induced PC12 cell injury. Furthermore, compounds 5a, 5d, 5e, 5f, and 5h presented good blood–brain barrier permeation in vitro and drug-like properties. More interesting, the PET/CT images with [¹¹C]5f demonstrated that [¹¹C]5f could penetrate the BBB with a high brain uptake and exhibited good brain clearance kinetic property. Therefore, compound 5f would be a promising multi-functional agent for the treatment of AD.     

基于MODIS NDVI的广西沿海植被动态及其主要驱动因素

归一化植被指数(NDVI)可以表征区域植被状况,目前利用NDVI表征沿海区域植被动态的研究仍相对缺乏。以MODIS NDVI为源数据,分析2000—2014年间,广西沿海区域的植被动态、NDVI动态趋势和持续性,以及NDVI动态的主要驱动因素。结果表明:在海岸线10 km区域范围内,NDVI均值较高(0.71),年际间波动较小(SD为0.02)。空间上,NDVI呈现出陆地高、滨海和河口区域低的分布特征,不同类型植被NDVI差异显著,以广泛分布于陆地的林地最高(0.76),以滨海湿地植被(0.52)和其他类型植被(未利用地等)最低(0.50)。植被动态趋势(斜率k)表明,57%的林地表现为改善趋势(k≥0.002),而52%的滨海湿地则表现为退化趋势(k≤-0.002)。利用Hurst指数对生态持续性进行分析,林地、旱地表现为持续改善,滨海湿地呈现持续退化的趋势。驱动因素分析表明,气象因素对植被NDVI的影响均不显著,NDVI的动态主要受地形特征和人为因素的影响,NDVI及其动态趋势与复合地形指数和距河流的距离多呈负相关,与坡度、高程、距交通线路和城镇的距离多为正相关。总体上,区域内NDVI动态趋势以良性发展为主,但滨海湿地等呈现持续退化的区域需持续关注。