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Leptin-induced Notch and IL-1 signaling crosstalk in endometrial adenocarcinoma is associated with invasiveness and chemoresistance

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World Journal of Clinical Oncology 2019年第6期10卷 222-233页

作者： Danielle Daley-Brown Adriana Harbuzariu Ann Anu Kurian Gabriela Oprea-Ilies Ruben Rene Gonzalez-Perez Department of Microbiology Biochemistry and Immunology Morehouse School of Medicine Atlanta GA 30310 United States Department of Pathology and Laboratory Medicine Emory University Atlanta GA 30322 United States

BACKGROUND Obesity is a recognized risk factor for endometrial cancer (EmCa) and other cancer types. Leptin levels are significantly increased in obese individuals. Leptin-induced signaling crosstalk [Notch, Interleukin-1 (IL-1) and leptin outcome, NILCO] has been associated with breast cancer progression. This complex signaling crosstalk affects cancer cell proliferation, migration, invasion, angiogenesis, apoptosis and chemoresistance. NILCO expression was previously detected in human EmCa. However, it is unknown whether leptin regulates NILCO and alters EmCa’s response to chemotherapeutics. It is hypothesized that leptin induces NILCO and increases aggressiveness and chemoresistance in EmCa cells. AIM To determine whether leptin induces NILCO molecules in EmCa affecting cell proliferation, aggressiveness and chemoresistance. METHODS Leptin’s effects on the expression of NILCO molecules [mRNAs and proteins for Notch receptors (Notch1-4), ligands (JAG1 and DLL4) and downstream effectors (survivin, Hey2), and leptin (OB-R) and IL-1 (IL-1R tI) receptors] was examined in EmCa cells (type I: Ishikawa, and HEC-1A, and type II: An3Ca and KLE) using Real-time PCR and Western blot analysis, respectively. In addition, the effects of leptin on cell cycle, proliferation and cell invasion were determined using cytometric analysis (Cellometer Vision CBA system), MTT cell proliferation and Matrigel-based invasion assays, respectively. Inhibitors of leptin (nanoparticlebound leptin peptide receptor antagonist-2, IONP-LPrA2), IL-1 (anti-IL-1R tI antibody) and Notch (siRNA interference RNA) were used to investigate NILCO’s effects on cell proliferation and invasion. Leptin’s effects on Paclitaxel cytotoxicity in EmCa cells was determined by the CCK8 and Cellometer-based Annexin V assays. RESULTS For the first time it was shown that leptin is an inducer of Notch in EmCa. Experimental data suggest that leptin induced the expression of NILCO molecules, promoted proliferation and S- phase progression, and reduced Paclitaxel cytotoxi

关键词： Endometrial cancer Leptin Notch Interleukin-1 Notch, IL-1 and Leptin crosstalk outcome Chemoresistance

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Tumor-stroma crosstalk对肝细胞癌中肝星状细胞氨基酸代谢水平的影响

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临床肝胆病杂志 2018年第12期34卷 2610-2613页

作者：吴静孟庆华薛冉首都医科大学附属北京佑安医院肝病重症医学科北京100069 首都医科大学附属北京朝阳医院消化内科北京100020

目的探讨tumor-stroma crosstalk对肝星状细胞(HSC)氨基酸代谢的影响。方法分别培养人肝癌细胞系HepG2、Hep3B、Huh7,以及LX-2 HSC。分别使用LX-2 HSC条件培养基(LX2-CM)和HepG2、Hep3B、Huh7肝癌细胞混合条件培养基(Hep-CM)培养HSC,并收集细胞上清,应用氨基酸分析仪检测细胞上清氨基酸谱变化。计量资料组间比较采用t检验。结果HSC氨基酸代谢水平改变情况,与对照组(LX2-CM)相比,实验组(Hep-CM)上清中瓜氨酸(t=3. 426,P=0. 027)、缬氨酸(t=2. 892,P=0. 045)、异亮氨酸(t=4. 224,P=0. 013)、亮氨酸(t=4. 150,P=0. 014)、酪氨酸(t=3. 556,P=0. 024)、苯丙氨酸(t=4. 023,P=0. 016)、赖氨酸(t=3. 369,P=0. 028)水平降低,差异均有统计学意义。结论肿瘤微环境中,tumor-stroma crosstalk可以影响HSC的氨基酸代谢水平,这种改变可能反过来促使肝癌细胞更加适应低氧微环境。

关键词：肝肿瘤氨基酸类代谢 tumor-stroma crosstalk

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crosstalk between innate and adaptive immunity in hepatitis B virus infection

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World Journal of Hepatology 2015年第30期7卷 2980-2991页

作者： Li Wang Kai Wang Zhi-Qiang Zou Infectious Disease Hospital of Yantai Hepatology Department Qilu Hospital Affiliated to Shandong University

Hepatitis B virus(HBV) infection is a major public healthproblem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is res-ponsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection.

关键词： crosstalk Hepatitis B virus Innate immune Adapative immune

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果蝇免疫通路crosstalk关键基因的筛选及其功能研究

果蝇免疫通路crosstalk关键基因的筛选及其功能研究

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作者：赵诣江苏科技大学

学位级别：硕士

果蝇(Drosophila melanogaster)是昆虫中研究最为深入的一种模式动物,其免疫系统被作为研究昆虫和人类先天免疫系统的模型。尽管果蝇免疫应答通路的研究已经取得了诸多的成果,但仍无法完全准确地反映先天免疫系统在应对免疫刺激时所表... 详细信息

果蝇(Drosophila melanogaster)是昆虫中研究最为深入的一种模式动物,其免疫系统被作为研究昆虫和人类先天免疫系统的模型。尽管果蝇免疫应答通路的研究已经取得了诸多的成果,但仍无法完全准确地反映先天免疫系统在应对免疫刺激时所表现出来的各种生理现象。其中一个重要的因素就是这些响应免疫刺激的通路并不是完全孤立的,而是通过一些基因或基因间的关系相互影响,甚至与其它非免疫通路之间存在彼此联系,构成信号传递和响应的网络。一个通路的变化将对其它通路也造成影响,形成通路间的crosstalk效应。本课题组前期利用对果蝇进行免疫刺激后的高通量实验数据,构建了果蝇免疫刺激后通路crosstalk网络以及相对应的基因互作网络,在此基础上筛选出一批与果蝇先天免疫通路crosstalk相关的候选基因,并从布鲁明顿果蝇库中获取了24个候选基因的果蝇突变品系。通过使用革兰氏阳性细菌藤黄微球菌(Micrococcus luteus)对这些突变品系果蝇进行显微注射并检测免疫刺激后24小时果蝇的生存率。通过多次免疫刺激实验筛选出比对照品系野生型w果蝇存活率显著降低的基因突变品系,发现载脂蛋白(apolpp)缺陷型果蝇的生存率明显低于对照品系w,该缺陷型果蝇是通过插入Minos转座元件的方式对apolpp基因序列造成了破坏。为检测apolpp基因受到破坏的具体情况,对Minos元件插入位点处的序列进行了PCR扩增,发现突变品系中apolpp基因中编码apo LppⅠ蛋白部分的序列提前出现终止密码子,该变化将导致apo LppⅠ蛋白无法正常合成。通过注射藤黄微球菌到果蝇体内,对apolpp缺陷型果蝇体内的菌落负荷进行统计,发现apolpp缺陷型体内的藤黄微球菌数量显著高于w果蝇。对apolpp缺陷型果蝇及对照品系w果蝇经藤黄微球菌和PBS刺激后进行转录组测序,筛选出4组样本间的显著差异表达基因,分别进行GO和KEGG的功能注释及通路富集分析,显示w在免疫刺激后检测到丝氨酸蛋白酶活性及“几丁质结合”功能,而在apolpp缺陷型中却没有。此外,藤黄微球菌感染后apolpp缺陷型中的“叶酸生物合成”通路被显著激活,而“淀粉和蔗糖代谢”和“半乳糖代谢”通路中的差异表达基因在w中均上调,但在apolpp缺陷型中均未发生明显变化。将差异表达基因映射在先前构建好的基因互作网络中,分析了apolpp缺陷型果蝇在免疫应答过程中的基因网络变化,并通过q RT-PCR技术进行了验证,结果表明apolpp在抵抗藤黄微球菌的过程中发挥重要作用。另外,apolpp缺陷型果蝇PGRP-SC1受体基因异常高表达而IMD通路的部分抗革兰氏阴性肽受到显著抑制,并在通过对apolpp突变品系注射大肠杆菌后的生存率实验中进一步证实,表明apolpp基因对免疫通路IMD的活性有着重要的影响。对转录组数据进行分析并通过q RT-PCR验证后发现细菌侵染将导致apolpp的表达被显著抑制;对Toll及IMD通路的3个重要转录因子dorsal、dif和relish突变品系果蝇免疫刺激后检验apolpp表达量的变化情况,结果显示3个突变体中apolpp表达量均下降,与对照w果蝇中的结果一致。可能是由于Toll与IMD通路并不是通过转录因子直接对apolpp的表达进行调节,另一种可能是3个转录因子间存在冗余关系,仅突变一个并不能影响对apolpp的调控作用。研究结果表明apolpp是果蝇先天免疫免疫通路crosstalk的关键基因,在果蝇响应细菌侵染中起重要作用。

关键词：果蝇先天免疫 crosstalk 载脂蛋白

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crosstalk-Aware Routing Resource Assignment

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Journal of Computer Science & Technology 2005年第2期20卷 231-236页

作者： Hai-LongYao Yi-CiCai QiangZhou Xian-LongHong DepartmentofComputerScienceandTechnology TsinghuaUniversityBeijing100084P.R.China

crosstalk noise is one of the emerging issues in deep sub-micrometer technology which causes many undesired effects on the circuit performance. In this paper, a crosstalk-Aware Routing Resource Assignment (CARRA) algorithm is proposed, which integrates the routing layers and tracks to address the crosstalk noise issue during the track/layer assignment stage. The CARRA problem is formulated as a weighted bipartite matching problem and solved using the linear assignment algorithm. The crosstalk risks between nets are represented by an undirected graph and the maximum number of the concurrent crosstalk risking nets is computed as the max clique of the graph. Then the nets in each max clique are assigned to disadjacent tracks. Thus the crosstalk noise can be avoided based on the clique concept. The algorithm is tested on IBM benchmarks and the experimental results show that it can improve the final routing layout a lot with little loss of the completion rate.

关键词： crosstalk interconnect physical design routing track/layer assignment VLSI

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crosstalk between the CBL-CIPK and SA signaling pathways in the wheat-Pucciniastriiformis f.sp.tritici pathosystem

Crosstalk between the CBL-CIPK and SA signaling pathways in ...

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第六届全国小麦基因组学及分子育种大会

作者： Jun Guo Peng Liu Yinghui Duan Jia Guo Zhensheng Kang State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection Northwest A&F University

Intracellular calcium changes during plant-pathogen interaction are essential early events leading to both local and systemic acquired resistances.Salicylic acid,a critical messenger,is also required for both responses.However,the relationship between the CBL-CIPK and SA signaling pathways during wheat-Pst interaction is unclear.In this study,we isolated seven wheat CBL and 11 wheat CIPK genes and designated them as TaCBL1,2,3,4,6,7,9 and TaCIPK2,5,7,9,10,14,15,17,23,31,32.Some wheat CBLs and CIPKs were functionally characterized.Concurrently,wheat TaNPR1 as a master regulator of SA-mediated host response during Pst infection was functionally characterized.Silencing of TaCIPK10 and TaNPR1 permitted increased rust development in a wheat variety that was resistant to Pst pathotype CYR23.Decreased levels of salicylic acid(SA) was observed in TaCIPK10-silenced wheat plants.Yeast two-hybrid and biomolecular fluorescence complementation(BiFC) revealed that TaCIPK10 interacted with TaNPR1.These results suggest that the crosstalk between CBL-CIPK and SA singaling pathway which is involved in innate immunity of wheat to Pst.

关键词： wheat CBL-CIPK SA crosstalk stripe rust fungus

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Design analysis for ultra-low crosstalk in high core count heterogeneous multicore fiber

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Optoelectronics Letters 2021年第10期17卷 616-621页

作者： Dablu Kumar Rakesh Ranjan OFC and Photonics Lab Department of Electronics and Communication EngineeringNational Institute of Technology PatnaPatna 800005India

Design analysis of high core count(36-core,37-core)un-coupled multicore fiber(MCF)using the heterogeneous core has been proposed,to achieve the high spatial efficiency and ultra-low crosstalk(~-81 d B/100 km)under the limited cladding diameter of 300μm.To realize the ultra-low crosstalk level between the neighboring cores,the combination of two crosstalk reduction approaches,trench-assisted(TA)core and propagation direction interleaving(PDI)technique has been used.The forward and backward crosstalk characterizations have been studied in heterogeneous MCF with respect to fiber bending radius,wavelength,transmission distance,and core-pitch with both normal step-index and trench-assisted cores under single-mode propagation condition.

关键词： crosstalk fiber trench

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Mode-and wavelength-multiplexed transmission with crosstalk mitigation using a single amplified spontaneous emission source

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Photonics Research 2019年第11期7卷 1363-1369页

作者： Yetian Huang Haoshuo Chen Hanzi Huang Zhengxuan Li Nicolas K.Fontaine Roland Ryf Juan Carlos Alvarado Rodrigo Amezcua-Correa John van Weerdenburg Chigo Okonkwo A.M.J.Koonen Yingxiong Song Min Wang Key Laboratory of Specialty Fiber Optics and Optical Access Networks Joint International Research Laboratory of Specialty Fiber Optics and Advanced CommunicationShanghai Institute for Advanced Communication and Data ScienceShanghai UniversityShanghai 200444China Nokia Bell Labs HolmdelNew Jersey 07733USA CREOL University of Central FloridaOrlandoFlorida 32816USA Institute for Photonic Integration Eindhoven University of Technology5600 MBEindhovenThe Netherlands

We propose to use the low-coherence property of amplified spontaneous emission(ASE) noise to mitigate optical crosstalk, such as spatial, polarization, and modal crosstalk, which currently limits the density of photonic integration and fibers for dense space-division multiplexing. High optical crosstalk tolerance can be achieved by ASE-based low-coherence matched detection, which avoids dedicated optical lasers and uses spectrally filtered ASE noise as the signal carrier and as a matched local oscillator. We experimentally demonstrate spatial and modal crosstalk reduction in multimode fiber(MMF) and realize mode-and wavelength-multiplexed transmission over1.5-km MMF supporting three spatial modes using a single ASE source. Performance degradation due to model dispersion over MMF is experimentally investigated.

关键词： crosstalk polarization matched

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Appropriate method of core selection and crosstalk optimization in single-mode homogeneous multicore fiber

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Optoelectronics Letters 2020年第2期16卷 126-130页

作者： DABLU Kumar RAKESH Ranjan Optical Fiber Communication and Photonics Lab Department of Electronics and Communication EngineeringNational Institute of Technology(NIT)PatnaPatna 800005India

The approach for homogeneous core structure design and selection based on low crosstalk, low dispersion, and acceptable mode effective area have been explored. The forward and backward crosstalk behaviors with respect to wavelength, fiber bending radius, and twisting rate in 12-core, and 21-core single-mode trench-assisted homogenous multicore fiber have been analyzed. The new expression for forward crosstalk under bending and twisting conditions has been derived using the conventional method. For the analysis and optimization of crosstalk, three different core structures are considered, it helps to draw the attention to select the appropriate core structure model for multicore fiber, which follows the standards used in telecom services.

关键词： crosstalk fiber trench

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基于MAPK与NOS信号crosstalk调控的EOFAZ对ox-LDL诱导HAECs损伤保护作用实验研究

基于MAPK与NOS信号Crosstalk调控的EOFAZ对ox-LDL诱导HAECs损伤保...

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作者：文波贵州医科大学

学位级别：硕士

目的:研究艳山姜挥发油（EOFAZ）对氧化低密度脂蛋白（ox-LDL）诱导损伤的人主动脉内皮细胞（HAECs）的保护作用及迁移和修复的影响,探索其保护作用是否与丝裂原活化蛋白激酶（MAPK）与一氧化氮合酶（NOS）信号相关联,同时探索MAPK与NO... 详细信息

目的:研究艳山姜挥发油（EOFAZ）对氧化低密度脂蛋白（ox-LDL）诱导损伤的人主动脉内皮细胞（HAECs）的保护作用及迁移和修复的影响,探索其保护作用是否与丝裂原活化蛋白激酶（MAPK）与一氧化氮合酶（NOS）信号相关联,同时探索MAPK与NOS信号之间是否存在crosstalk调控,阐明EOFAZ保护作用机制,为血管内皮功能失调相关疾病的预防和治疗提供实验基础和理论指导。方法:（1）EOFAZ保护作用研究分为7组:正常对照组（control,无血清ECM）,模型组（ox-LDL,200 mg/L ox-LDL）,EOFAZ高剂量组（200 mg/L ox-LDL+100μg/L EOFAZ）,EOFAZ低剂量组（200 mg/L ox-LDL+10μg/L EOFAZ）,阿司匹林组（Asp.,200 mg/L ox-LDL+2.5×10-4 mol/L Aspirin）,卡维地洛组（Car.,200 mg/L ox-LDL+1×10-6 mol/L Carvedilol）,阿托伐他汀钙组（Atov.,200 mg/L ox-LDL+1×10-6 mol/L Atorvastatin Calcium）。（2）EOFAZ对细胞迁移与修复作用研究分为4组:正常对照组（control,0.5%ECM）,模型组（ox-LDL,200 mg/L ox-LDL+0.5%ECM）,EOFAZ高剂量组（200 mg/L ox-LDL+100μg/L EOFAZ+0.5%ECM）,EOFAZ低剂量组（200 mg/L ox-LDL+10μg/L EOFAZ+0.5%ECM）。（3）MAPK信号研究分为5组:正常对照组（无血清ECM）,模型组（200 mg/L ox-LDL）,EOFAZ组（200 mg/L ox-LDL+100μg/L EOFAZ）,MAPK抑制剂组（200 mg/L ox-LDL+40μmol/LSB203580或5μmol/L SP600125或10μmol/L PD98059）,EOFAZ加MAPK抑制剂组（200 mg/L ox-LDL+100μg/L EOFAZ+40μmol/L SB203580或5μmol/L SP600125或10μmol/L PD98059）。（4）NOS信号研究分为5组:对照组（无血清ECM）,模型组（200 mg/L ox-LDL）,EOFAZ组（200 mg/L ox-LDL+100μg/L EOFAZ）,NOS抑制剂组（200 mg/L ox-LDL+100μmol/L L-NAME或300μmol/L L-NMMA）,EOFAZ加NOS抑制剂组（200 mg/L ox-LDL+100μg/L EOFAZ+100μmol/L L-NAME或300μmol/L L-NMMA）。（5）MAPK抑制剂crosstalk调控NOS信号研究实验分为7组:对照组（无血清ECM）,模型组（200 mg/L ox-LDL）,EOFAZ组（200 mg/L ox-LDL+100μg/L EOFAZ）,nos抑制剂组（200mg/lox-ldl+100μmol/ll-name或300μmol/ll-nmma）,p38mapk抑制剂组（200mg/lox-ldl+40μmol/lsb203580）,jnk1/2/3抑制剂组（200mg/lox-ldl+5μmol/lsp600125）,erk1/2抑制剂组（200mg/lox-ldl+10μmol/lpd98059）。（6）nos抑制剂crosstalk调控mapk信号研究分为5组:对照组（无血清ecm）,模型组（200mg/lox-ldl）,eofaz组（200mg/lox-ldl+100μg/leofaz）,mapk抑制剂组（200mg/lox-ldl+40μmol/lsb203580或5μmol/lsp600125或10μmol/lpd98059）,nos抑制剂组（200mg/lox-ldl+100μmol/ll-name或300μmol/ll-nmma）。体外培养haecs,用ox-ldl复制细胞损伤模型,加入eofaz、阿司匹林、卡维地洛、阿托伐他汀钙、mapk或nos各抑制剂干预保护1h后,继续加入ox-ldl继续作用24h。采用mtt法分析细胞存活率,确定ox-ldl诱导细胞损伤的最佳浓度与时间。倒置显微镜观察细胞损伤形态,吉姆萨（giemsa）和苏木精-伊红（he）染色观察细胞损伤病理学特征。划痕试验（woundscratchassay）进行细胞迁移距离与修复分析,微孔滤膜培养小室及双室联合培养系统（transwell）分析细胞迁移率。分别用酶标仪法、elisa法分析细胞损伤的乳酸脱氢酶（ldh）和一氧化氮（no）含量。化学法检测结构型一氧化氮合酶（enos）和诱导型一氧化氮合酶（inos）含量。实时荧光定量聚合酶链式反应（quant

关键词：艳山姜挥发油氧化低密度脂蛋白人主动脉内皮细胞丝裂原活化蛋白激酶一氧化氮合酶 crosstalk

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