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敲降低密度脂蛋白受体相关蛋白表达对肝癌血管异常化的影响及其机制

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中华肿瘤杂志 2024年第5期46卷 399-408页

作者：武强詹琳琳王宇贺钰超陈璐陈子叶李广涛刘东明包旭刘潇濛郭华宋天强天津医科大学肿瘤医院肝胆肿瘤科国家恶性肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津300060 天津医科大学肿瘤医院肿瘤细胞生物学实验室国家恶性肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津300060 北京清华长庚医院临床转化科学中心北京102218

目的探讨低密度脂蛋白受体相关蛋白(LDLR)表达对肝癌血管异常化的影响及其机制。方法从Oncomine癌症基因芯片数据库提取87例肝癌组织的基因转录组信息,分析肝癌组织中LDLR的表达水平与癌胚抗原(CEA)和CD31表达水平的相关性。采用短发卡... 详细信息

目的探讨低密度脂蛋白受体相关蛋白(LDLR)表达对肝癌血管异常化的影响及其机制。方法从Oncomine癌症基因芯片数据库提取87例肝癌组织的基因转录组信息,分析肝癌组织中LDLR的表达水平与癌胚抗原(CEA)和CD31表达水平的相关性。采用短发卡RNA靶基因慢病毒转染的方法,构建LDLR敲降的MHCC-97H和HLE肝癌细胞。通过转录组测序、实时荧光定量聚合酶链反应、蛋白免疫印迹法检测LDLR敲降后肝癌细胞的差异基因及其表达水平变化。通过富集分析明确LDLR参与的基因相关信号通路。通过对肝癌细胞条件培养基中CEA含量的检测评估LDLR对CEA的影响。采用血管生成实验检测LDLR对人脐静脉内皮细胞血管生成能力的影响,以及CEA在LDLR调控血管生成过程中的作用。收集2019年1月至2022年12月于天津医科大学肿瘤医院手术切除的肝癌组织标本176例,采用免疫组织化学染色检测176例肝癌组织中LDLR及146例肝癌组织中CEA和CD31的表达水平,分析肝癌组织中LDLR的表达水平与肝癌组织中CEA和CD31的表达水平、血清CEA和丙氨酸氨基转移酶(ALT)水平的相关性。结果Oncomine数据库分析显示,发生门静脉转移的肝癌患者肝癌组织中LDLR和CEA的表达呈负相关(r=-0.64,P=0.001),而CEA和CD31的表达呈正相关(r=0.46,P=0.010);转录组测序结果显示,LDLR敲降组与对照组MHCC-97H细胞的差异表达基因共有1032个,其中517个基因表达上调,515个基因表达下调。CEA相关细胞黏附分子5(CEACAM5)在LDLR敲降组细胞中上调明显。基因本体论功能富集分析显示,差异基因最明显富集在血管生成的功能上。京都基因与基因组百科全书信号通路富集分析显示,涉及的相关通路主要包括细胞粘着斑、细胞外基质受体相互作用等。LDLR敲降组条件培养基中CEA含量为43.75±8.43,高于对照组(1.15±0.14,P<0.001)。血管生成实验结果显示,在5 h,用LDLR敲降组MHCC-97H细胞的条件培养基培养HUVEC细胞形成的血管主结点数、主分段数和网格总面积分别为(295.3±26.4)个、(552.5±63.8)个和(2239781.0±138211.9)平方像素,均高于对照组[分别为(113.3±23.5)个、(194.8±36.5)个和(660621.0±280328.3)平方像素,均P<0.01];用LDLR敲降组HLE细胞的条件培养基培养HUVEC细胞形成的血管主结点数、主分段数和网格总面积分别为(245.3±42.4)个、(257.5±20.4)个和(2535754.5±249094.2)平方像素,均高于对照组[分别为(113.3±23.5)个、(114.3±12.2)个和(1565456.5±219259.7)平方像素,均P<0.01];在对照组MHCC-97H细胞条件培养基中加入CEA培养HUVEC细胞形成的血管主结点数、主分段数和网格总面积分别为(178.9±12.0)个、(286.9±12.3)个和(1966990.0±126249.5)平方像素,均高于对照组[分别为(119.7±22.1)个、(202.7±33.7)个和(1421191.0±189837.8)平方像素,均P<0.01]。肝癌组织中LDLR的表达与CEA的表达无相关性,与肝癌组织中CD31的表达、血清CEA水平、血清ALT水平均呈负相关(r=-0.167,P=0.044;r=-0.061,P=0.032;r=-0.147,P=0.05)。肝癌组织中CEA的表达与CD31的表达呈正相关(r=0.192,P=0.020),血清CEA水平与血清ALT水平呈正相关(r=0.164,P=0.029)。结论肝癌细胞敲降LDLR可通过释放CEA促进肝癌血管异常化。

关键词：肝细胞癌低密度脂蛋白受体相关蛋白癌胚抗原血管生成

Cytosolic phospholipase A2α modulates cell-matrix adhesion via the FAK/paxillin pathway in hepatocellular carcinoma

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Cancer Biology & Medicine 2019年第2期16卷 377-390页

作者： Piao Guo yuchao he Lu Chen Lisha Qi Dongming Liu Ziye Chen Manyu Xiao Liwei Chen Yi Luo Ning Zhang Hua Guo Department of Tumor Cell Biology Department of hepatobiliary Cancer Department of Pathology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer/ Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for Cancer Tianjin 300060 China

Objective: To explore the effect of cytosolic phospholipase A2α(cPLA2α) on hepatocellular carcinoma(HCC) cell adhesion and the underlying ***: Cell adhesion, detachment, and hanging-drop assays were utilized to examine the effect of cPLA2α on the cell-matrix and cell-cell adhesion. Downstream substrates and effectors of cPLA2α were screened via a phospho-antibody *** signaling pathways were identified by the functional annotation tool DAVID. Candidate proteins were verified using Western blot and colocalization was investigated via immunofluorescence. Western blot and immunohistochemistry were used to detect protein expression in HCC tissues. Prognosis evaluation was conducted using Kaplan-Meier and Cox-proportional hazards regression ***: Our findings showed that cPLA2α knockdown decreases cell-matrix adhesion but increases cell-cell adhesion in hepG2 cells. Microarray analysis revealed that phosphorylation of multiple proteins at specific sites were regulated by cPLA2α. These phosphorylated proteins were involved in various biological processes. In addition, our results indicated that the focal adhesion pathway was highly enriched in the cPLA2α-relevant signaling pathway. Furthermore, cPLA2α was found to elevate phosphorylation levels of FAK and paxillin, two crucial components of focal adhesion. Moreover, localization of p-FAK to focal adhesions in the plasma membrane was significantly reduced with the downregulation of cPLA2α. Clinically, cPLA2α expression was positively correlated with p-FAK levels. Additionally, high expression of both cPLA2α and p-FAK predicted the worst prognoses for HCC ***: Our study indicated that cPLA2α may promote cell-matrix adhesion via the FAK/paxillin pathway, which partly explains the malignant cPLA2α phenotype seen in HCC.

关键词： hepatocellular carcinoma cytosolic phospholipase A2α cell-matrix adhesion FAK paxillin

Supersaturation-driven self-assembly formation of ceftriaxone sodium spherulites:From amorphous form to spherulites

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Particuology 2024年第7期90卷 10-19页

作者： Shankun Liang yuchao Niu Xueyan Hu Wu Xiao Xuehua Ruan Gaohong he Xiaobin Jiang State Key Laboratory of Fine Chemicals Frontiers Science Center for Smart MaterialsSchool of Chemical EngineeringDalian University of TechnologyDalian116024China School of Chemical Engineering at Panjin Dalian University of TechnologyPanjin124221China

Drug particles with spherical morphology possess amazing advantages in terms of particle flowability,mechanical properties,drug solubility,and *** growth mechanism of drug spherulite is of great importance for the preparation and regulation of ***,ceftriaxone sodium spherulites were fabricated by the antisolvent crystallization method using dropwise addition of ceftriaxone sodium solution to *** observation of the whole crystallization process combined with electron microscopy technique revealed the spherical growth process from amorphous form to *** the supersaturation of the crystallization system was adjusted,the ceftriaxone sodium crystals transformed from amorphous form to *** the process of antisolvent crystallization with acetone as antisolvent,when the theoretical supersaturation degree S was higher than 2.62,the crystallization system tended to appear amorphous form;when S was between 2.57 and 2.62,the amorphous form transformed into clustered spherulites;when S was less than 2.57,the surface of spherulites will be covered with flaky crystal,which transformed into urchin-like *** the understanding of the spherical growth mechanism,the ceftriaxone sodium spherulites prepared in this research with modified supersaturation control had a low residue of antisolvent acetone,and the flowability was significantly improved.

关键词： Spherulite Ceftriaxone sodium Antisolvent crystallization Supersaturation Online observation

Periostin mediates epithelial-mesenchymal transition through the MAPK/ERK pathway in hepatoblastoma

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Cancer Biology & Medicine 2019年第1期16卷 89-99页

作者： Lu Chen Xiangdong Tian Wenchen Gong Bo Sun Guangtao Li Dongming Liu Piao Guo yuchao he Ziye Chen Yuren Xia Tianqiang Song Hua Guo Department of Tumor Cell Biology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: The aim of the present study was to analyze the prognostic factors in patients with hepatoblastoma(HB) in our single center and to evaluate periostin(POSTN) expression in HB and its association with clinicopathological variables. In addition, the underlying mechanism of how POSTN promotes HB progression was ***: POSTN expression was investigated in HB tumors by immunohistochemistry(IHC), immunofluorescence(IF) and Western blot(WB). The association among POSTN expression, clinicopathological features and overall survival(OS) was also evaluated. The migration and adhesion ability of HB cells were measured using chemotaxis and cell-matrix adhesion assays,respectively. Epithelial-mesenchymal transition(EMT)-associated markers and activation of the ERK pathway were detected by ***: HB patients had poor prognosis which displayed lymph node metastasis, vascular invasion, POSTN and vimentin expression. POSTN expression was also associated with lymph node metastasis. Furthermore, overexpressed POSTN promoted migration and the adhesive ability of HB cells in vitro. In addition, we demonstrated that POSTN activated the MAPK/ERK pathway, upregulated the expression of Snail and decreased the expression of OVOL2. Finally, POSTN promoted the expression of EMT-associated ***: POSTN might modulate EMT via the ERK signaling pathway, thereby promoting cellular migration and *** study also suggests that POSTN may serve as a therapeutic biomarker in HB patients.

关键词： Periostin hepatoblastoma EMT MAPK/ERK

Restoring cellular calcium homeostasis to rescue ER stress by 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid acetoxymethyl ester-loaded lipid-mPLGA hybrid-nanoparticles for acute kidney injury therapy

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Chinese Chemical Letters 2024年第3期35卷 337-345页

作者： Jingwen Zhang Jiahui Yan Yanan Wang Hong Liu Xueping Sun yuchao Gu Liangmin Yu Changcheng Li Jun Wu Zhiyu he Frontiers Science Center for Deep Ocean Multispheres and Earth System and Key Laboratory of Marine Chemistry Theory and TechnologyMinistry of EducationOcean University of ChinaQingdao 266100China College of Chemistry and Chemical Engineering Ocean University of ChinaQingdao 266100China School of Medicine and Pharmacy Ocean University of ChinaQingdao 266003China Sanya Oceanographic Institution Ocean University of ChinaQingdao 572024China Bioscience and Biomedical Engineering Thrust The Hong Kong University of Science and Technology(Guangzhou)NanshaGuangzhou 511400China Division of Life Science The Hong Kong University of Science and TechnologyHong Kong 999077China

Early pathogenesis of ischemia-reperfusion(I/R)-induced acute kidney injury(AKI)is dominated by intracellular calcium overload,which induces oxidative stress,intracellular energy metabolism disorder,inflammatory activation,and a series of pathologic cascaded reactions that are closely intertwined with self-amplifying and interactive feedback loops,ultimately resulting in cell damage and kidney ***,most nanomedicines originate from the perspective of antioxidant stress,which can only quench existing reactive oxide species(ROS)but cannot prevent the continuous production of ROS,resulting in insufficient *** a safe and promising drug,BAPTA-AM is hydrolyzed into BAPTA by intracellular esterase upon entering cells,which can rapidly chelate with overloaded Ca^(2+),restoring intracellular calcium homeostasis,thus inhibiting ROS regeneration at the ***,we designed a KTP-targeting peptide-modified yolk-shell structure of liposome–poly(ethylene glycol)methyl ether-block-poly(L-lactide-co-glycolic)(mPLGA)hybrid nanoparticles(he characteristics of high encapsulation rate,high colloid stability,facile modification,and prolonged blood circulation *** the BA/mPLGA@Lipo-KTP was targeted to the site of kidney injury,the cholesteryl hemisuccinate(CheMS)in the phospholipid bilayer,as an acidic cholesterol ester,was protonated in the simulated inflammatory slightly acidic environment(pH 6.5),causing the liposomes to rupture and release the BA/mPLGA nanoparticles,which were then depolymerized by intracellular *** BAPTA-AM was diffused and hydrolyzed to produce BAPTA,which can rapidly cut off the malignant loop of calcium overload/ROS generation at its source,blocking the endoplasmic reticulum(ER)apoptosis pathway(ATF4–CHOP–Bax/Bcl-2,Casp-12–Casp-3)and the inflammatory pathway(TNF-α–NF-κB–IL-6 axes),thus alleviating pathological changes in kidney tissue,thereby inhibiting the expression of renal tubular marker kidney injury mole

关键词： BAPTA-AM Calcium overload Acid-responsive AKI ER stress

Genomic Surveillance for SARS-CoV-2 Variants: Dominance of XBB Replacement — China, January–June 2023

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China CDC weekly 2024年第15期6卷 324-331页

作者： Yenan Feng Qiudong Su Lili Li Xiaozhou he Peihua Niu Xiaojuan Guo Xiang Zhao Jing Tang Zhiyuan Jia Ji Wang Changcheng Wu Baicheng Xia Zhixiao Chen yuchao Wu Jing Yang Songqi Chen Cao Chen Shiwen Wang Xiaoping Dong National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina NHC Key Laboratory of Medical Virology and Viral Diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina

Introduction:In the first half of 2023,a global shift was observed towards the predominance of XBB *** faced a significant epidemic between late 2022 and early 2023 due to Omicron subvariants BA.5.2 and *** study aims to depict the evolving variant distribution among provincial-level administrative divisions(PLADs)in China and explore the factors driving the predominance of XBB ***:Sequences from local and imported coronavirus disease 2019(COVID-19)cases recorded between January 1 and June 30,2023,were *** study analyzed the changing distribution of viral variants and assessed how the prior dominance of specific variants,XBB subvariants,and imported cases influenced the prevalence of the XBB replacement ***:A total of 56,486 sequences were obtained from local cases,and 8,669 sequences were from imported *** in April,there was a shift in the prevalence of XBB from imported to local cases,with varying dominance among *** PLADs previously high in BF.7,the rise of XBB was delayed.A positive correlation was found between XBB proportions in imported cases from January to March and local cases in *** distribution pattern of XBB subvariants differed between local and imported cases within the same *** significant differences were noted in the replacement rates of XBB ***:The timing of XBB dominance differed among various PLADs in China in the first half of 2023,correlating closely with the prevalence of XBB variants among imported cases.

关键词： dominance imported distribution

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云岭自然保护区黑白仰鼻猴监测初报

林业调查规划 2015年第2期40卷 68-73页

作者：和育超兰坪县林业局云南兰坪671400

云岭省级自然保护区从2008年起采用长期巡护监测路线和临时路线相结合的方式,对黑白仰鼻猴种群进行不间断地监测。结果表明,截至2012年,区内分布有3个黑白仰鼻猴种群,数量约350只,各猴群的种群数量和组成结构存在差异,繁育高峰期各有不... 详细信息

云岭省级自然保护区从2008年起采用长期巡护监测路线和临时路线相结合的方式,对黑白仰鼻猴种群进行不间断地监测。结果表明,截至2012年,区内分布有3个黑白仰鼻猴种群,数量约350只,各猴群的种群数量和组成结构存在差异,繁育高峰期各有不同。由于各种群呈岛屿状分布,季节性活动区域比较固定,非外因改变路线情况罕有;受干扰因素影响,被动选取栖息地的情况时有发生;种群数量增幅与天敌假说有关。对猴群的家域范围、干扰因素以及行为活动进行分析,针对存在的问题提出保护及管理建议。

关键词：黑白仰鼻猴种群监测行为活动栖息地危机云岭自然保护区

石墨烯作为水基半合成切削液添加剂的硬质合金-钢材料摩擦学特性分析

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国防科技大学学报 2018年第4期40卷 142-150页

作者：姚斌何昱超孙维方曹新城陈彬强郑清厦门大学航空航天学院福建厦门361005

改善加工过程润滑条件是延缓刀具磨损的重要途径。将石墨烯作为3034水基半合成切削液的添加剂,研究石墨烯悬浮切削液的硬质合金-钢材料摩擦学性能,研究对象是由硬质合金YG8制备的金属球和由45#钢制备的圆盘形试件;采用球-盘摩擦副接触... 详细信息

改善加工过程润滑条件是延缓刀具磨损的重要途径。将石墨烯作为3034水基半合成切削液的添加剂,研究石墨烯悬浮切削液的硬质合金-钢材料摩擦学性能,研究对象是由硬质合金YG8制备的金属球和由45#钢制备的圆盘形试件;采用球-盘摩擦副接触方式在摩擦磨损试验机上进行试验,测定了质量分数为0. 1%~0. 9%的石墨烯悬浮切削液的平均摩擦特性和摩擦系数;采用激光共聚焦显微镜对磨痕轮廓进行提取,并得出磨损定量评价指数,并用扫描电镜和拉曼光谱仪对磨痕进行磨损机理分析;进行切削实验来分析石墨烯悬浮切削液对切削性能指标的改善情况。实验分析结果表明:石墨烯悬浮切削液能明显改善硬质合金-45#钢之间的润滑条件,摩擦系数和磨损率显著下降,采用不同质量分数石墨烯悬浮切削液的平均摩擦系数较原半合成切削液下降12. 9%~57. 3%,磨损率下降33. 82%,同时切削合力较原半合成切削液下降18. 58%,加工后工件表面粗糙度下降7. 5%。

关键词：石墨烯硬质合金水基半合成切削液摩擦学特性

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关于加气混凝土砌块墙体质量控制的探讨

城市建筑 2014年第18期11卷 161-162页

作者：贺玉超中国江西国际经济技术合作公司南昌330046

加气混凝土砌块是建筑墙体中较为常见的砌块，加气混凝土砌块墙体裂缝问题在建筑房屋墙体中比较常见，给建筑施工企业带来了极大的麻烦。文章对导致墙体开裂的因素进行了深入分析，并提出了有效地防治及改善措施。

关键词：加气混凝土砌块墙体裂缝防治措施