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Rehan Ali Sandeep Apte Marta Vilalta Murugesan Subbarayan Zheng Miao Frederick T. Chin Edward E. Graves 《PloS one》2015,10(10)
We evaluated the relationship between pre-treatment positron emission tomography (PET) using the hypoxic tracer 18F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] (18F-EF5) and the response of preclinical tumor models to a range of fractionated radiotherapies. Subcutaneous HT29, A549 and RKO tumors grown in nude mice were imaged using 18F-EF5 positron emission tomography (PET) in order to characterize the extent and heterogeneity of hypoxia in these systems. Based on these results, 80 A549 tumors were subsequently grown and imaged using 18F-EF5 PET, and then treated with one, two, or four fraction radiation treatments to a total dose of 10–40 Gy. Response was monitored by serial caliper measurements of tumor volume. Longitudinal post-treatment 18F-EF5 PET imaging was performed on a subset of tumors. Terminal histologic analysis was performed to validate 18F-EF5 PET measures of hypoxia. EF5-positive tumors responded more poorly to low dose single fraction irradiation relative to EF5-negative tumors, however both groups responded similarly to larger single fraction doses. Irradiated tumors exhibited reduced 18F-EF5 uptake one month after treatment compared to control tumors. These findings indicate that pre- treatment 18F-EF5 PET can predict the response of tumors to single fraction radiation treatment. However, increasing the number of fractions delivered abrogates the difference in response between tumors with high and low EF5 uptake pre-treatment, in agreement with traditional radiobiology. 相似文献
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Wen-feng Xiao Yu-sheng Li Ang Deng Yun-tao Yang Miao He 《Cell biochemistry and function》2020,38(2):122-129
The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up-regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix-degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of HH gene is not an option for OA treatment in humans because it is not possible to delete HH in larger animals. Efficient knockdown of HH achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions. 相似文献
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基于指标自动筛选的新疆开孔河流域生态健康评价 总被引:1,自引:0,他引:1
生态健康评价对了解区域生态健康状况和促进区域可持续发展具有重要意义,如何自动筛选出能反映生态系统特性的重要指标,是生态健康定量评估的关键问题。基于压力-状态-响应(PSR,Press-State-Response)框架和生态等级网络框架(EHN,Ecological Hierarchy Network),通过文献调研和因果分析建立要素层与指标层之间的交叉联系,构建了生态健康评价"网状"指标体系;在保证指标体系完备性基础上,通过结合主成分分析和熵权法的候选指标权重的客观计算,基于目标优化理论构建了评价指标的自动筛选模型,并基于中选指标计算了新疆开孔河流域2001—2017年生态健康指数(EHCI,Ecological Health Comprehensive Indexes),分析其空间分异和时间变化特征。结果表明:利用所建立的评价指标自动筛选模型,开孔河流域生态健康评价指标由31个候选指标自动筛选出了17个中选指标,用54.8%的指标表达了85.98%的信息,中选的17个指标在干旱/半干旱区域有关文献中应用较多,使用频次比例都在20%以上,其中归一化植被指数(NDVI,Normalized Difference Vegetation Index)、年降水量和植被覆盖度(FVC,Fractional Vegetation Coverage)3个指标的使用频次百分比均超过了50%,说明指标自动筛选模型的合理性;开孔河流域空间分布差异显著,总体上西北高、东南低,东南部和中部绿洲区外围生态健康状况较差,西北部河谷地带和中部两大绿洲区生态健康状况较好;17年来,流域生态质量整体趋于改善,显著改善区域占10.26%,远高于显著退化的1.61%,显著改善区域以孔雀河绿洲最为明显。开孔河流域生态健康的总体好转趋势说明区域生态综合治理取得一定成效。 相似文献
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In the developing wheat grain, photosynthate is transferred longitudinally along the crease phloem and then laterally into the endosperm cavity through the crease vascular parenchyma, pigment strand and nucellar projection. In order to clarify this cellular pathway of photosynthate unloading, and hence the controlling mechanism of grain filling, the potential for symplastic and apoplastic transfer was examined through structural and histochemical studies on these tissue types. It was found that cells in the crease region from the phloem to the nucellar projection are interconnected by numerous plasmodesmata and have dense cytoplasm with abundant mitochondria. Histochemical studies confirmed that, at the stage of grain development studied, an apoplastic barrier exists in the cell walls of the pigment strand. This barrier is composed of lignin, phenolics and suberin. The potential capacity for symplastic transfer, determined by measuring plasmodesmatal frequencies and computing potential sucrose fluxes through these plasmodesmata, indicated that there is sufficient plasmodesmatal cross-sectional area to support symplastic unloading of photosynthate at the rate required for normal grain growth. The potential capacity for membrane transport of sucrose to the apoplast was assessed by measuring plasma membrane surface areas of the various cell types and computing potential plasma membrane fluxes of sucrose. These fluxes indicated that the combined plasma membrane surface areas of the sieve element–companion cell (se–cc) complexes, vascular parenchyma and pigment strand are not sufficient to allow sucrose transfer to the apoplast at the observed rates. In contrast, the wall ingrowths of the transfer cells in the nucellar projection amplify the membrane surface area up to 22-fold, supporting the observed rates of sucrose transfer into the endosperm cavity. We conclude that photosynthate moves via the symplast from the se–cc complexes to the nucellar projection transfer cells, from where it is transferred across the plasma membrane into the endosperm cavity. The apoplastic barrier in the pigment strand is considered to restrict solute movement to the symplast and block apoplastic solute exchange between maternal and embryonic tissues. The implications of this cellular pathway in relation to the control of photosynthate transfer in the developing grain are discussed. 相似文献