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排序方式: 共有242条查询结果,搜索用时 31 毫秒
1.
Haiyan Miao Jingjing Lu Yibing Guo Hongquan Qiu Yu Zhang Xihao Yao Xiaohong Li Yuhua Lu 《Journal of cellular and molecular medicine》2021,25(7):3654-3664
Pancreatic ductal adenocarcinoma (PDAC) is an invasive and aggressive cancer that remains a major threat to human health across the globe. Despite advances in cancer treatments and diagnosis, the prognosis of PDAC patients remains poor. New and more effective PDAC therapies are therefore urgently required. In this study, we identified a novel host factor, namely the LncRNA TP73-AS1, as overexpressed in PDAC tissues compared to adjacent healthy tissue samples. The overexpression of TP-73-AS1 was found to correlate with both PDAC stage and lymph node metastasis. To reveal its role in PDCA, we targeted TP73-AS1 using LnRNA inhibitors in a range of pancreatic cancer (PC) cell lines. We found that the inhibition of TP73-AS1 led to a loss of MMP14 expression in PC cells and significantly inhibited their migratory and invasive capacity. No effects of TP73-AS1 on cell survival or proliferation were observed. Mechanistically, we found that TP73-AS1 suppressed the expression of the known oncogenic miR-200a. Taken together, these data highlight the prognostic potential of TP73-AS1 for PC patients and highlight it as a potential anti-PDAC therapeutic target. 相似文献
2.
鸡胚血液中原始生殖细胞的分离及其培养的研究 总被引:2,自引:0,他引:2
从孵化48~55小时鸡胚中抽取血液,每只胚胎可获血液2~6μl左右。一步法离心分离原始生殖细胞,可使其浓度由0.1%以下提高到50%以上。将多余血细胞用微量吸管移走后,加入添加10%胎牛血清的TCM—199做为培养基,37.5℃,5%CO2,95%空气,饱和湿度下培养,原始生殖细胞可成活24小时左右。 相似文献
3.
四川55种鱼生活史型的研究 总被引:1,自引:0,他引:1
四川55种鱼生活史型的研究刁晓明,罗一兵李波(西南农业大学水产系,重庆630716)(重庆大学计算机系,630000)LifeHistoryPatternsof55FishSpeciesinSichuan¥DiaoXiaoming;LuoYibing... 相似文献
4.
5.
Yibing Xu Jianping Sun Michael A. Sheard Hung C. Tran Zesheng Wan Wei Yao Liu Shahab Asgharzadeh Richard Sposto Hong Wei Wu Robert C. Seeger 《Cancer immunology, immunotherapy : CII》2013,62(10):1637-1648
Background
Treatment for children with high-risk neuroblastoma with anti-disialoganglioside mAb ch14.18, IL-2, and GM-CSF plus 13-cis-retinoic acid after myeloablative chemotherapy improves survival, but 40 % of patients still relapse during or after this therapy. The microenvironment of high-risk neuroblastoma tumors includes macrophages, IL-6, and TGFβ1. We hypothesized that this microenvironment suppresses anti-tumor functions of natural killer (NK) cells and that lenalidomide, an immune-modulating drug, could overcome suppression.Methods
Purified NK cells were cultured with IL-2, neuroblastoma/monocyte-conditioned culture medium (CM), IL-6, TGFβ1, and lenalidomide in various combinations and then characterized using cytotoxicity (direct and antibody-dependent cell-mediated cytotoxicity), cytokine, flow cytometry, and Western blotting assays. Anti-tumor activity of NK cells with lenalidomide, ch14.18, or both was evaluated with a xenograft model of neuroblastoma.Results
CM from neuroblastoma/monocyte co-cultures contains IL-6 and TGFβ1 that suppress IL-2 activation of NK cell cytotoxicity and IFNγ secretion. IL-6 and TGFβ1 activate the STAT3 and SMAD2/3 pathways in NK cells and suppress IL-2 induction of cytotoxicity, granzymes A and B release, perforin expression, and IFNγ secretion. Lenalidomide blocks IL-6 and TGFβ1 activation of these signaling pathways and inhibits their suppression of NK cells. Neuroblastoma cells in NOD/SCID mice exhibit activated STAT3 and SMAD2/3 pathways. Their growth is most effectively inhibited by co-injected peripheral blood mononuclear cells (PBMC) containing NK cells when mice are treated with both ch14.18 and lenalidomide.Conclusion
Immunotherapy with anti-tumor cell antibodies may be improved by lenalidomide, which enhances activation of NK cells and inhibits their suppression by IL-6 and TGFβ1. 相似文献6.
Irisin, which was recently identified as a myokine and an adipokine, transforms white adipose tissue to brown adipose tissue and has increasingly caught the attention of the medical and scientific community. However, the signaling pathway of irisin and the molecular mechanisms responsible for the lipolysis effect remain unclear. In this study, we established an efficient system for the expression and purification of GST-irisin in Escherichia coli. The biological activity of GST-irisin was verified using the cell counting kit-8 assay and by detecting the mRNA expression of uncoupling protein 1. Our data showed that GST-irisin regulates mRNA levels of lipolysis-related genes such as adipose triglyceride lipase and hormone-sensitive lipase and proteins such as the fatty acid-binding protein 4, leading to increased secretion of glycerol and decreased lipid accumulation in 3T3-L1 adipocytes. In addition, exogenous GST-irisin can increase its autocrine function in vitro by regulating the expression of fibronectin type III domain-containing protein 5. GST-irisin could regulate glucose uptake in 3T3-L1 adipocytes. Hence, we believe that recombinant GST-irisin could promote lipolysis and its secretion in vitro and can potentially prevent obesity and related metabolic diseases. 相似文献
7.
Effects of plant hedgerows on soil erosion and soil fertility on sloping farmland in the purple soil area 下载免费PDF全文
Effect of using plant hedgerows on controlling soil and water losses has received wide recognition and this technology has been applied in many areas in the world. Yet, studies on the effect of using plant hedgerows on soil fertility on sloping lands are rare. Carrying out an eight-year fixed field experiment, the authors investigated the effect of two different hedgerows against the control treatment on soil fertility. Results showed that clay particles tended to accumulate in front of the plant hedgerows and began to erode downward below the hedgerows along the contour lines across the field. Distribution of soil organic matter and all plant nutrients except potassium (K) showed the same pattern as the clay particles. Potassium, however, was evenly distributed in the field without any noticeable influence from the hedgerows. Since the fixed experiment started, soil phosphorus (P) kept accumulating, while soil organic matter and K were in depletion. The results accordingly suggested better nutrient management practices on the sloping lands by using properly reduced rates of P and increased rates of farm manure and K. Taking the sloping field as a whole, special attention in nutrient management should be given to the soil strips —the portions below the plant hedgerows suffering from more serious soil erosion. 相似文献
8.
The renewal and differentiation of Isl1+ cardiovascular progenitors are controlled by a Wnt/beta-catenin pathway 总被引:3,自引:0,他引:3
Qyang Y Martin-Puig S Chiravuri M Chen S Xu H Bu L Jiang X Lin L Granger A Moretti A Caron L Wu X Clarke J Taketo MM Laugwitz KL Moon RT Gruber P Evans SM Ding S Chien KR 《Cell Stem Cell》2007,1(2):165-179
Isl1(+) cardiovascular progenitors and their downstream progeny play a pivotal role in cardiogenesis and lineage diversification of the heart. The mechanisms that control their renewal and differentiation are largely unknown. Herein, we show that the Wnt/beta-catenin pathway is a major component by which cardiac mesenchymal cells modulate the prespecification, renewal, and differentiation of isl1(+) cardiovascular progenitors. This microenvironment can be reconstituted by a Wnt3a-secreting feeder layer with ES cell-derived, embryonic, and postnatal isl1(+) cardiovascular progenitors. In vivo activation of beta-catenin signaling in isl1(+) progenitors of the secondary heart field leads to their massive accumulation, inhibition of differentiation, and outflow tract (OFT) morphogenic defects. In addition, the mitosis rate in OFT myocytes is significantly reduced following beta-catenin deletion in isl1(+) precursors. Agents that manipulate Wnt signals can markedly expand isl1(+) progenitors from human neonatal hearts, a key advance toward the cloning of human isl1(+) heart progenitors. 相似文献
9.
Juan Fan Jiawei Shi Yong Zhang Junwei Liu Chenyi An Huaying Zhu Peng Wu Wei Hu Rui Qin Danmei Yao Xin Shou Yibing Xu Zhou Tong Xue Wen Jianpo Xu Jin Zhang Weijia Fang Jizhong Lou Weiwei Yin Wei Chen 《The EMBO journal》2022,41(2)
Stimulatory immune receptor NKG2D binds diverse ligands to elicit differential anti‐tumor and anti‐virus immune responses. Two conflicting degeneracy recognition models based on static crystal structures and in‐solution binding affinities have been considered for almost two decades. Whether and how NKG2D recognizes and discriminates diverse ligands still remain unclear. Using live‐cell‐based single‐molecule biomechanical assay, we characterized the in situ binding kinetics of NKG2D interacting with different ligands in the absence or presence of mechanical force. We found that mechanical force application selectively prolonged NKG2D interaction lifetimes with the ligands MICA and MICB, but not with ULBPs, and that force‐strengthened binding is much more pronounced for MICA than for other ligands. We also integrated steered molecular dynamics simulations and mutagenesis to reveal force‐induced rotational conformational changes of MICA, involving formation of additional hydrogen bonds on its binding interface with NKG2D, impeding MICA dissociation under force. We further provided a kinetic triggering model to reveal that force‐dependent affinity determines NKG2D ligand discrimination and its downstream NK cell activation. Together, our results demonstrate that NKG2D has a discrimination power to recognize different ligands, which depends on selective mechanical force‐induced ligand conformational changes. 相似文献
10.
Yibing Shan Venkatesh P. Mysore Abba E. Leffler Eric T. Kim Shiori Sagawa David E. Shaw 《PLoS computational biology》2022,18(3)
Protein-protein interactions (PPIs) are ubiquitous biomolecular processes that are central to virtually all aspects of cellular function. Identifying small molecules that modulate specific disease-related PPIs is a strategy with enormous promise for drug discovery. The design of drugs to disrupt PPIs is challenging, however, because many potential drug-binding sites at PPI interfaces are “cryptic”: When unoccupied by a ligand, cryptic sites are often flat and featureless, and thus not readily recognizable in crystal structures, with the geometric and chemical characteristics of typical small-molecule binding sites only emerging upon ligand binding. The rational design of small molecules to inhibit specific PPIs would benefit from a better understanding of how such molecules bind at PPI interfaces. To this end, we have conducted unbiased, all-atom MD simulations of the binding of four small-molecule inhibitors (SP4206 and three SP4206 analogs) to interleukin 2 (IL2)—which performs its function by forming a PPI with its receptor—without incorporating any prior structural information about the ligands’ binding. In multiple binding events, a small molecule settled into a stable binding pose at the PPI interface of IL2, resulting in a protein–small-molecule binding site and pose virtually identical to that observed in an existing crystal structure of the IL2-SP4206 complex. Binding of the small molecule stabilized the IL2 binding groove, which when the small molecule was not bound emerged only transiently and incompletely. Moreover, free energy perturbation (FEP) calculations successfully distinguished between the native and non-native IL2–small-molecule binding poses found in the simulations, suggesting that binding simulations in combination with FEP may provide an effective tool for identifying cryptic binding sites and determining the binding poses of small molecules designed to disrupt PPI interfaces by binding to such sites. 相似文献