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In situ construction of ligand nano-network to integrin αvβ3 for angiogenesis inhibition

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Chinese Chemical Letters 2020年第12期31卷 3107-3112页

作者： Ziming Chen Kuo Zhang Jiaqi Fan Yu Fan Chao Yang Wen Tian Yuan Li Wenliang Li Jingping Zhang Hao Wang Lei Wang Faculty of Chemistry Northeast Normal UniversityChangchun 130024China CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and Technology(NCNST)Beijing 100190China

Angiogenesis occurs during the process of tumor growth,invasion and metastasis,and is essential for the survival of solid *** an integrin significantly ove rexpressed in human tumor vascular endothelial cells,αvβ3 is a suitable targeting site for anti-angiogenesis of *** designed and prepared a selfassembling peptide(SAP)with the ability to targeting αvβ3 and *** formed nanoparticles in solution and transformed into nanofibrous network once specifically binding to integrin αvβ3 on the surface of human umbilical vein endothelial cells(HUvECs).The SAP network stably anchored on HUvECs over 24h,which consequently resulted in high-efficient inhibition of *** vitro anti-angiogenesis experiment displayed that the inhibition rate of tube-formation reached 94.9%.In vivo anti-angiogenesis array based on chick chorioallantoic membrane(CAM)model exhibited that the SAP had an inhibition rate up to 63.1%.These results indicated the outstanding anti-angiogenic ability of SAP,potentially for tumor therapy.

关键词： Self-assembly integrinαvβ3 Peptide Anti-angiogenesis Tumor

CXCR4通过integrinαvβ3调控头颈部鳞癌细胞迁移的机制研究

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现代肿瘤医学 2023年第9期31卷 1584-1588页

作者：常艳艳李鹏孟金平陈艳艳河南省肿瘤医院头颈甲状腺科河南郑州450000

目的:研究C-X-C型趋化因子受体4(CXCR4)-整合素αvβ3(integrinαvβ3)介导头颈部鳞癌细胞迁移的分子生物学机制。方法:应用头颈部鳞癌细胞株HN-5,采用慢病毒转染方法构建CXCR4过表达的细胞株,用荧光显微镜观察基因表达情况;采用脂质体... 详细信息

目的:研究C-X-C型趋化因子受体4(CXCR4)-整合素αvβ3(integrinαvβ3)介导头颈部鳞癌细胞迁移的分子生物学机制。方法:应用头颈部鳞癌细胞株HN-5,采用慢病毒转染方法构建CXCR4过表达的细胞株,用荧光显微镜观察基因表达情况;采用脂质体法将CXCR4-siRNA、integrinαvβ3-siRNA分别转染至HN-5细胞和CXCR4过表达的HN-5细胞中,Transwell小室实验检测HN-5细胞迁移能力,Western blot实验检测CXCR4、integrinαvβ3、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-2(MMP-2)和黏附斑激酶(FAK)-非受体型酪氨酸蛋白激酶(SRC)-细胞外信号调节激酶(ERK)信号通路相关蛋白的表达情况。结果:CXCR4过表达可上调HN-5细胞中integrinαvβ3表达水平,而抑制CXCR4表达可下调integrinαvβ3表达;CXCR4过表达可调控MMP-2和MMP-9促进癌细胞迁移,并激活FAK-SRC-ERK信号通路;而抑制integrinαvβ3表达可明显逆转CXCR4过表达对HN-5细胞的上述作用。结论:CXCR4过表达可通过integrinαvβ3促进头颈部鳞癌细胞迁移,其作用机制可能与激活FAK-SRC-ERK通路有关。

关键词： CXCR4 integrinαvβ3 头颈部鳞癌细胞迁移

Effects of controlled superovulation on the expression of HOXA10,integrin αvβ3 and LIF in mice during peri-implantation

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Journal of Hainan Medical University 2021年第8期27卷 7-11页

作者： Lei Zhang Jie Liu Ying Zhang Fang Wang Chang-Lei Li Ai-Ni Fu Jun You Shu-Xiu Zhu School of medicine JianghanUniversityWuhan 430056China Center for Reproductive Medicine Maternal and Child Health Hospital of Hubei ProvinceWuhan 430070China

Objective:To observe the expression of endometrial homologous box gene A10(HOXA10),integrinαvβ3 and leukemia suppressor factor(LIF)in peri-implantation mice,and to investigate the effect of controlled superovulation(COH)on endometrial receptivity in ***:After COH model preparation and blastocyst transplantation,kunming pure-bred mature mice were randomly divided into natural blastocyst+natural pseudocyst group,COH blastocyst+natural pseudocyst group,natural blastocyst+COH pseudocyst group,and COH blastocyst+COH pseudocyst *** pregnancy rate and average number of beds in each group were observed on day 6 of *** blot and RT-PCR were used to detect the expression of HOXA10,integrinααvβ3,LIF protein and mRNA in the endometria of mice on day 5 of ***:The pregnancy rate and average number of beds in the COH group were lower than those in the natural receptor *** expression of HOXA10,integrinααvβ3 and LIF in endometrium was significantly lower than that of the natural receptor mice(Pvulation drugs down-regulate the expression of HOXA10,integrinαvβ3 and LIF in endometrium during the implantation window,reduce endometrial receptivity,and lead to low clinical pregnancy rate.

关键词： Controlled superovulation Endometrial receptivity Homologous box gene A10 integrinαvβ3 Leukemia suppressor

Combination Therapy with LXW7 and Ceria Nanoparticles Protects against Acute Cerebral Ischemia/Reperfusion Injury in Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2018年第1期38卷 144-152页

作者： Ting ZHANG Chang-yan LI Jing-jing JIA Jie-shan CHI Da ZHOU Jian-zhou LI Xiao-ma LIU Jun ZHANG Li YI Department of Neurology Peking University Shenzhen HospitalShenzhen 518000China College of Chemistry and Chemical Engineering Inner Mongolia UniversityHohhot 010021China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China

Ischemia/reperfusion is known to greatly increase oxidative stress in the penumbra,which results in brain ***αvβ3 is selectively up-regulated with ischemic injury to the brain and remains elevated throughout *** determined whether or not a new compound biotinylated-LXW7-ceria nanoparticle(Ce NP)(b LXW7-Ce NP)plays a role in brain protection in the rat model of middle cerebral artery occlusion/reperfusion and shows better effects than Ce NPs alone in improving the outcomes of focal oxidative stress and apoptosis more *** Sprague-Dawley rats were subjected to focal cerebral ischemia for 2 h followed by a 24-h *** treatment was intravenously administered via the caudal vein 1 h after *** were randomly divided into the following 4 groups:b LXW7-Ce NP treatment group(0.5 mg/kg);Ce NP treatment group(0.5 mg/kg);control saline group;and sham *** were harvested 24 h after reperfusion,and the neurologic deficit scores,infarction volume,blood-brain barrier(BBB)disruption,and the level of oxidative stress and apoptosis were *** showed that the b LXW7-Ce NP and Ce NP treatments could improve neurologic deficit scores,infarction volume,BBB disruption,and the level of oxidative stress and *** b LXW7-Ce NP treatment exhibited better effects than Ce Np treatment and showed remarkable statistical differences in the infarction volume,the degree of BBB breakdown,the apoptosis and oxidative stress,apart from neurologic deficit ***,we concluded that b LXW7-Ce NP protects against acute cerebral ischemia/reperfusion ***7,as a ligand of integrinαvβ3,may be able to effectively localize the anti-oxidant Ce NPs to the ischemic penumbra region,which may provide more adequate opportunities for Ce NPs to exert anti-oxidative stress effects and subsequently reduce apoptosis in acute cerebral ischemia/reperfusion.

关键词： ceria nanoparticles integrinαvβ3 LXW7 cerebral ischemia oxidative stress

Effects of Jiawei Buzhong Yiqi Decoction on the Endometrial Receptivity of Rats with Polycystic Ovary Syndrome

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Medicinal Plant 2021年第6期12卷 46-49,55页

作者： Chen ZHAO Chenggang LI Hubei University of Medicine Shiyan 442000 China

[Objectives]The study aims to discuss the effects of Jiawei Buzhong Yiqi Decoction on the endometrial receptivity of rats with polycystic ovarian syndrome(PCOS).[Methods]Adult female SD rats were selected and randomly divided into the model group and control *** the model group,the PCOS model was established by using the method of Poretsky *** in the control group were given physiological saline intervention at the same *** successfully modeled rats were randomly divided into the PCOS group and traditional Chinese medicine *** them,rats in the Chinese medicine group were given Jiawei Buzhong Yiqi Decoction by gavage;rats in the model group and the control group were given normal saline for 14 *** rats were killed by anesthesia after the last administration,and serum and uterine specimens were *** sex hormones(including T,E_(2),and P),glucose and insulin levels were detected;the equivalent diameter and area of endometrial gland and gland cavity,and the endometrial thickness of rats were measured;the expression of endometrial leukemia inhibitory factor(LIF),integrinαvβ3 protein and mRNA was detected by using Elisa and RT-PCR methods.[Results]The serum T,glucose,and insulin levels of rats in the PCOS group were significantly higher than those of the control group and the traditional Chinese medicine group,and there was no significant difference in the above indicators between the control group and the traditional Chinese medicine group;there was no significant difference in the E_(2) and P levels between the three *** equivalent diameter and area of endometrial gland and gland cavity,and the endometrial thickness of rats in the PCOS group were lower than those of the control group and the traditional Chinese medicine group;there was no significant difference in the above indicators between the traditional Chinese medicine group and the control *** expression of LIF,integrinαvβ3 protein and mRNA in the endometrium of rats

关键词： Jiawei Buzhong Yiqi Decoction Polycystic ovary syndrome Leukemia inhibitory factor integrinαvβ3

放射性核素标记RGD小肽在肿瘤显像及治疗中的应用进展

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云南大学学报（自然科学版） 2009年第S1期31卷 527-529页

作者：洪愉曾韦锟成都军区昆明总医院核医学科云南昆明650032 昆明理工大学生命科学与技术学院云南昆明650224

integrinαvβ3在肿瘤新生血管中高表达,是肿瘤诊断与治疗的重要靶点.放射性核素标记的RGD小肽能够与integrinαvβ3特异性结合,从而达到肿瘤显像和治疗的目的,具有良好的应用前景.

关键词：肿瘤靶向 integrinαvβ3 放射性核素

流体剪应力对去卵巢骨质疏松大鼠破骨细胞骨吸收功能的影响

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流体剪应力对去卵巢骨质疏松大鼠破骨细胞骨吸收功能的影响

作者：刘应芬四川大学

学位级别：硕士

研究背景骨质疏松症(Osteoporosis，OP)是中老年人的一种常见病，是以骨量减少、骨组织微观结构退化为特征，致使骨的脆性增高而骨折危险性增加的一种全身性疾病。一般情况下，3位女性有1人易患骨质疏松症，而男性一般是12人中有1人患... 详细信息

研究背景骨质疏松症(Osteoporosis，OP)是中老年人的一种常见病，是以骨量减少、骨组织微观结构退化为特征，致使骨的脆性增高而骨折危险性增加的一种全身性疾病。一般情况下，3位女性有1人易患骨质疏松症，而男性一般是12人中有1人患骨质疏松症。可见，骨质疏松症是发病率、死亡率和医疗保健消耗较大的疾病。因此，骨质疏松症的预防和治疗是很重要的。影响骨质疏松症发生发展的因素有很多，力学负荷是其重要因素之一。体外研究已证实，力学负荷在正常骨组织的发育过程中具有重要的作用。骨组织中的腔隙结构构成纵横交错的三维网络，这些腔隙中充满了组织液。正常活动对骨组织施加的机械负荷，将引起这些腔隙体积的变化，从而形成液压促进流动，因此认为在骨组织内，这种液体的流动产生的剪应力可能在骨的生长发育过程中发挥了重要作用。然而，破骨细胞对剪应力是否敏感，破骨细胞是如何将力学刺激信号转换成生物化学信号，在骨质疏松中破骨细胞对力学刺激的敏感性是否有变化，目前仍不清楚。因此，我们假设，破骨细胞和前提破骨细胞是剪应力敏感细胞，破骨细胞表面integrinαβ参与破骨细胞中力学信号转导。本研究的目的就是：1)探讨剪应力对正常和去卵巢骨质疏松大鼠破骨细胞骨吸收功能活性的影响;2)探讨破骨细胞integrinαβ在力学信号传导中可能的分子机理。研究方法 1．骨质疏松动物模型的建立选用健康6月龄雌性未生育Sprague-Dawley(SD)大鼠，采用双侧卵巢切除术，建立模拟人绝经后骨质疏松动物模型。动物实验分为2组：对照组(control)，不切除卵巢、卵巢切除组(ovx)，切除双侧卵巢。手术后3个月处死动物，检测动物体重、子宫重量;做骨组织病理学切片，观察骨组织形态学和骨细胞功能活性的变化，以确定模型建立成功。 2．破骨细胞体外培养无菌分离大鼠腰椎(L)，采用机械分离法和1，25-(OH)vitD全骨髓诱导法相结合，从大鼠椎骨骨髓细胞中获取破骨细胞，以细胞形态、TRAP染色阳性、骨吸收陷窝的形成、细胞骨架等指标观察、鉴定破骨细胞。 3．羟基磷灰石涂层盖玻片的制备由于对骨片的加力装置设计较难，考虑人体内骨组织无机成分主要是羟基磷灰石。因此，我们采用羟基磷灰石涂层血盖片的方法来模拟体内骨基质吸收情况。以Ca(NO)·4HO和PO为原材料，采用溶胶-凝胶法制备羟基磷灰石涂层盖玻片，模拟破骨细胞在骨片上的骨吸收情况。 4．剪应力对破骨细胞功能活性影响的检测 1)采用本室自制的流体剪应力加载系统对所选用的破骨细胞分别施加0、5.97、11.36、16.08、20.54dyne/cm的剪应力，作用30min;每次剪应力作用结束后，收集灌流液10ml冻存，备用。用紫外分光光度仪检测TRAP活性;采用羟基磷灰石涂层盖玻片模拟体内骨基质吸收情况，以扫描电子显微镜和图像分析软件检测骨吸收陷窝数量和面积，观察不同剪应力强度对正常和骨质疏松大鼠破骨细胞功能活性的影响;2)再根据以上实验结果，选取对破骨细胞功能活性影响最大的剪应力强度，观察剪应力作用不同时间，正常和骨质疏松大鼠破骨细胞骨吸收功能活性的变化;5．剪应力对破骨细胞表面用integrinαβ表达影响的检测采用细胞免疫组织化学技术检测剪应力作用对破骨细胞表面integrinαβ表达的影响 6．破骨细胞表面integrinαβ表达量与破骨细胞骨吸收功能关系分析用integrinββ单克隆抗体(sc-7312)孵育破骨细胞30min，阻断破骨细胞表面integrinαβ的表达，对破骨细胞作用相同的剪应力，同样用扫描电子显微镜技术和图像分析软件分析破骨细胞骨吸收功能的变化。结果 1．去卵巢手术后3个月，OvX组大鼠体重明显增加(p＜0.01);子宫明显萎缩，重量降低(p＜0.01);骨组织病理学切片显示骨小梁分离、断裂，数量减少，骨髓腔内含有大量脂肪细胞，骨胶原中有大量新生胶原纤维形成，破骨细胞骨吸收残迹明显增加，符合骨质疏松的特点。 2．以机械分离法和1，25-(OH)vitD全骨髓诱导法相结合从大鼠椎骨骨髓细胞中获取破骨细胞，在诱导培养第7天，所获破骨细胞数量最多，TRAP活性最佳。且在培养第1天骨质疏松组大鼠破骨细胞数和TRAP活性高于正常大鼠组。 3．羟基磷灰石(HA)涂层盖玻片可模拟骨基质吸收情况，破骨细胞在HA盖玻片上培养可以形成骨吸收陷窝。 4．在我们所选用的剪应力范围内，作用破骨细胞30min后，正常大鼠和骨质疏松大鼠破骨细胞TRAP活性、骨吸收陷窝数量和面积均较静态时增高(P＜0.01)，以16.08dyne/cm的剪应力作用最明显;但骨质疏松大鼠破骨细胞功能活性的增高低于正常大鼠破骨细胞(p＜0.05)。 5．16.08dyne/cm的剪应力作用破骨细胞不同时段，随着作用时间延长，破骨细胞骨吸收陷窝数量和

关键词：流体剪应力羟基磷灰石 integrinαvβ3 破骨细胞去卵巢骨质疏松大鼠