Implication of Expression of Osteopontin and Its Receptor Integrin αvβ3 in the Placenta in the Development of Preeclampsia

To investigate the expression of osteopontin （OPN） and its receptor integrin αvβ3 in the placental tissue from pregnant women complicated with preeclampsia, the expression of OPN and αvβ3 in the placenta of the pregnant women with preeclampsia and healthy pregnant women was detected by immunohistochemistry, Western blotting and RT-PCR. Our results showed that OPN and αvβ3 protein were expressed in the placenta from normal pregnant woman and those with preeclampsia. OPN was located in the placental syncytiotrophoblasts and the cytoplasm of capillary endothelial cells and integrin αvβ3 was mainly expressed on the surface of trophoblast cells. Expression of OPN and integrin αvβ3 in the placental tissue from preeclampsia subjects was significantly lower than that from the control group （P〈0.05）. Compared with the control group, expression of OPN in the placental tissue from preeclampsia group was significantly lower （P〈0.05） but there was no significant difference in the expression of αv and β3 between the preeclampsia group and the controls. It is concluded that OPN and its receptor integrin αvβ3 may be involved in the pathogenesis of preeclampsia.

Effects of Integrins and Integrin αvβ3 Inhibitor on Angiogenesis in Cerebral Ischemic Stroke

Summary： Integrins such as αvβ3, α5β31 play a key role in angiogenesis regulation, invasion and metastasis, inflammation, wound healing, etc. The up-regulation of integrin αvβ3 after cerebral ischemic stroke can promote angiogenesis, which in turn improves functional recovery. In addition, the integrin αvβ3 inhibitor can block the blood-brain barrier （BBB） leakage induced by vascular endothelial growth factor （VEGF） and also can reduce inflammatory reaction, decrease the deposition of fibrinogen. Other studies showed that integrin αvβ3 is not essential in revascularization. Therefore, the effect of integrin αvβ3 in the whole process of brain function recovery merits further study.

Effect of lentivirus-mediated integrin αVβ3-sh RNA on tumor growth of mice with lung cancer xenografts

Objective: To study the effect of lentivirus-mediated integrin αVβ3-sh RNA on tumor growth of mice with lung cancer xenograft. Methods: Lung cancer tissue, paracancer tissue and normal tissue were collected and integrin αVβ3 expression was detected; BALB/c nude mice were selected, divided into integrin αVβ3 knockdown group(KD group) and negative control group(NC group), and inoculated with cells stably infected by integrin αVβ3-sh RNA lentivirus and cells stably infected by negative control-sh RNA lentivirus respectively, the growth of tumor tissue was continuously observed, and the number of apoptosis cells as well as the expression of angiogenesis, apoptosis and invasion genes in tumor tissue were detected. Results: m RNA content and protein content of integrin αVβ3 in lung cancer tissue were significantly higher than those in paracancer tissue and normal tissue; increasing trend of tumor tissue volume of KD group was weaker than that of NC group, and tumor volume at various points in time of KD group was lower than that of NC group; m RNA contents and protein contents of VEGF, FGF, EGF, Bcl-2, MMP-9, MMP-12 and MMP-13 in tumor tissue of KD group were lower than those of NC group, and apoptosis index as well as m RNA content and protein content of Bax were higher than those of NC group. Conclusions: The expression of integrin αVβ3 increases in lung cancer tissue, and lentivirus-mediated integrin αVβ3-sh RNA can inhibit tumor growth of mice with lung cancer xenografts.

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

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 mice.Methods: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 group.The pregnancy rate and average number of beds in each group were observed on day 6 of conception.Western 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 conception.Results:The pregnancy rate and average number of beds in the COH group were lower than those in the natural receptor group.The expression of HOXA10,Integrinααvβ3 and LIF in endometrium was significantly lower than that of the natural receptor mice(P<0.01).Conclusion:Superovulation 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.

Integrin α_vβ_3靶向超声微泡的制备及体外寻靶实验

目的制备Integrinαvβ3靶向超声微泡,对其一般理化性质及体外寻靶能力进行检测。方法采用巯基-马来酰亚胺连接法制备携FITC标记iRGD肽的Integrinαvβ3靶向微泡(MBIntegrinαvβ3),并制备空白微泡(MBcontrol)。检测两组微泡的一般理化性质,在荧光显微镜下观察两组微泡荧光显像,流式细胞仪检测两组微泡FITC荧光含量。于光学显微镜及荧光显微镜下观察两组微泡与小鼠脑微血管内皮细胞(bEnd.3)的黏附情况。结果 1MBIntegrinαvβ3粒径为(0.84±0.26)μm,与MBcontrol粒径(0.79±0.19)μm差异无统计学意义(P>0.05);2荧光显微镜下观察,MBcontrol组微泡无荧光显示,MBIntegrinαvβ3组微泡表面显示绿色荧光;3流式细胞仪测得MBIntegrinαvβ3组微泡FITC荧光含量为98.4%,MBcontrol组微泡FITC荧光含量为2.5%;4体外寻靶实验显示,MBIntegrinαvβ3组微泡能聚集结合于bEnd.3细胞表面。结论成功制备了携iRGD肽的Integrinαvβ3靶向微泡,其具有良好的体外寻靶能力。

Ischemic preconditioning partially suppresses and postpones integrin α_Vβ_3 mRNA expression following transient global cerebral ischemia in C57BL/6 mice

Previous studies of integrin αvβ3 have focused on ischemic brain damage, although the role of integrin αvβ3 in ischemic preconditioning （IP） has rarely been reported. The present study analyzed the effects of IP on integrin αvβ3 mRNA expression following cerebral ischemia through the use of hematoxylin-eosin staining and real-time quantitative polymerase chain reaction techniques. Integrin avid3 mRNA expression in the ischemia group peaked at 24 hours after ischemia-reperfusion. In the IP ＋ ischemia group, integrin αvβ3 mRNA expression increased after 24 hours, but remained significantly less than the ischemia group, and expression continued to increase until 7 days after ischemiaJreperfusion. These results demonstrate that IP effectively attenuated upregulation of integrin αvβ3 mRNA expression at 24 hours after ischemia.

Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.

粘附分子CD44V6及Integrinαvβ_3在胆囊癌中的表达及意义

目的研究粘附分子CD44V6及Integrinαvβ_3在胆囊癌组织及胆囊炎中表达是否存在统计学意义的差异,其表达量与胆囊癌的分化程度之间的关系。方法应用免疫组织化学的方法检测20例胆囊癌及20例慢性胆囊炎组织中CD44V6及Integrinαvβ_3的表达,结合临床病理结果进行分析。结果在胆囊癌中CD44V6和Integrinαvβ_3表达阳性率分别为80.0%和70.0%。CD44V6及Integrinαvβ_3在胆囊癌中表达存在协同性,与胆囊癌分化程度呈正相关(均P<0.05)。结论 CD44V6及Integrinαvβ_3在胆囊癌中高表达(显著高于对照组),并且随着胆囊癌的分化程度降低其表达阳性分值增高;CD44V6及Integrinαvβ_3的表达与原发性胆囊癌的良恶性及分化程度相关;在相同标本中,CD44V6高表达往往伴有Integrinαvβ_3高表达,在胆囊癌的诊断上具有一致性,可联合作为临床监测胆囊癌发生、转移的参考指标。

Non-invasively differentiate non-alcoholic steatohepatitis by visualizing hepatic integrinαvβ3 expression with a targeted molecular imaging modality

BACKGROUND Non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH),an inflammatory subtype of non-alcoholic fatty liver disease(NAFLD),are currently unavailable.AIM To develop an integrinαvβ3-targeted molecular imaging modality to differentiate NASH.METHODS Integrinαvβ3 expression was assessed in Human LO2 hepatocytes Scultured with palmitic and oleic acids(FFA).Hepatic integrinαvβ3 expression was analyzed in rabbits fed a high-fat diet(HFD)and in rats fed a high-fat,high-carbohydrate diet(HFCD).After synthesis,cyclic arginine-glycine-aspartic acid peptide(cRGD)was labeled with gadolinium(Gd)and used as a contrast agent in magnetic resonance imaging(MRI)performed on mice fed with HFCD.RESULTS Integrinαvβ3 was markedly expressed on FFA-cultured hepatocytes,unlike the control hepatocytes.Hepatic integrinαvβ3 expression significantly increased in both HFD-fed rabbits and HFCD-fed rats as simple fatty liver(FL)progressed to steatohepatitis.The distribution of integrinαvβ3 in the liver of NASH cases largely overlapped with albumin-positive staining areas.In comparison to mice with simple FL,the relative liver MRI-T1 signal value at 60 minutes post-injection of Gd-labeled cRGD was significantly increased in mice with steatohepatitis(P<0.05),showing a positive correlation with the NAFLD activity score(r=0.945;P<0.01).Hepatic integrinαvβ3 expression was significantly upregulated during NASH development,with hepatocytes being the primary cells expressing integrinαvβ3.CONCLUSION After using Gd-labeled cRGD as a tracer,NASH was successfully distinguished by visualizing hepatic integrinαvβ3 expression with MRI.

Inhibitory Effects of Alpha-zearalenol on Angiotensin II-Induced Integrin β_3 mRNA via Suppression of Nuclear Factor-κB

To investigate the effect of α-zearalenol on angiotensin If-induced β3 integrin mRNA expression in human umbilical vein endothelial cells （HUVECs）. Methods The mRNA level in integrin β3 was determined by reverse transcription-polymerase chain reaction. Endothelial NF-κB activity was determined by the luciferase activity assay of plasmid NF-κB-LUC. Results The angiotensin Ⅱ- induced β3 integrin mRNA expression was inhibited by α-zearalenol and 17β-estradiol （10nmol/L ^-1 μmol/L）, but not influenced by ICI 182, 780, a pure competitive antagonist for estrogen receptor or a nitric oxide inhibitor N^ω-Nitro-L-arginine methyl ester hydrochloride. Alpha-zearalenol and 17β-estradiol suppressed the angiotensin Ⅱ-induced activation of NF-κB in endothelial cells. Condusion Alpha-zearalenol inhibits angiotensin Ⅱ-induced integrin β3 mRNA expression by suppressing NF-κB activation in endothelial cells.

The Expression of Integrin β_3 and Intercellular Adhesion Molecule(ICAM-1) in Decidua and Chorionic Villi during Mifepristone Induced Abortion

The effects of mifepristone with misoprostol on the expression of the integrin β 3 and intercellular adhesion molecule 1 (ICAM 1) in decidua and chorionic villi tissues in early pregnancy in 10 cases were investigated by immuno flow cytometry (the experiment group). At the same time, the other 10 cases induced by mechanical vacuum aspiration were collected as the control. The results showed that, the positive rate of integrin β 3 and ICAM 1 in decidua of the experiment group were 19.1±5.01% and 20.61 ±6.51%; while those in chorionic villi were 21.32±4.38% and 20.29± 6.49%, which were significantly lower than those in the control group. These results suggested that integrin β 3 and ICAM 1 may take part in the maintenance of early pregnancy. The mechanism of mifepristone induced abortion may be mediated by the down regulation of the integrin β 3 and ICAM 1 expression in decidua and chorionic villi.

microSPECT/CT显像定量评价肿瘤^(99m)Tc-3P4-RGD_2摄取及整合素α_Vβ_3表达水平的实验研究

目的:探讨99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2(简称99mTc-3P4-RGD2)microSPECT/CT显像定量肿瘤放射性摄取及整合素αvβ3表达水平的可行性研究。方法:对不同99mTc样品进行microSPECT/CT显像,评价样品体积、活度对放射性计数的影响;对荷脑胶质瘤裸鼠行99mTc-3P4-RGD2microSPECT/CT显像,对比基于CT、SPECT及融合图像测定的肿瘤体积与肿瘤实际体积一致性,并评价肿瘤整合素αvβ3表达水平,由病理证实。结果:99mTc样品microSPECT/CT显像放射性计数与其放射性活度呈直线相关(R2=0.999 7),Bland-Altman一致性分析显示,基于microSPECT/CT测定的肿瘤体积与肿瘤实际体积差异(%)为-2.48±8.17,显著低于microCT(15.04±79.53,t=5.60,P=0.005)和microSPECT(17.04±36.27,t=7.17,P=0.002);microSPECT/CT显像肿瘤99mTc-3P-RGD2摄取与整合素αvβ3表达呈正相关。结论:microSPECT/CT显像可定量99mTc放射性活度和成活肿瘤组织体积,有效评估整合素αvβ3受体表达,为肿瘤整合素受体靶向治疗患者筛选及药物剂量个体化提供影像学数据。

整合素α_vβ_3和骨桥蛋白在多囊卵巢综合征患者植入窗期子宫内膜的表达

目的探讨整合素α_vβ_3和骨桥蛋白(OPN)在多囊卵巢综合征(PCOS)患者植入窗期子宫内膜的表达。方法选取15名典型PCOS患者(其中7例为自主排卵,8例为促排卵)为PCOS组,同期选择15例月经周期规律妇女为对照组。阴道超声监测排卵,排卵日测定子宫内膜分型及厚度;免疫组织化学技术测定植入窗期的子宫内膜整合素α_vβ_3和骨桥蛋白的表达;放射免疫法测定内膜活检当天的血清雌二醇(E_2)和孕酮(P)的浓度。结果与对照组比较,PCOS组植入窗期子宫内膜整合素α_vβ_3和OPN表达均显著下调(P<0.01),两者之间不伴有比例的失调;排卵日子宫内膜厚度两组无显著差异(P>0.05);子宫内膜分型有显著性差异(P<0.05);血清E_2水平显著高于对照组(P<0.01),E_2/P比值亦显著高于对照组(P<0.05),而P显著低于对照组(P<0.01)。结论 PCOS患者植入窗期子宫内膜整合素α_vβ_3和OPN表达均下调,子宫内膜容受性降低,影响了胚泡着床。

整合素α_vβ_3和VEGF在前列腺癌的表达及临床意义

目的探讨整合素αvβ3和血管内皮生长因子(VEGF)在前列腺癌(PCa)中的表达及意义。方法应用免疫组织化学链酶抗生物素蛋白-过氧化物酶连接法(SP法)检测整合素αvβ3和VEGF在41例前列腺癌中的表达,20例正常前列腺组织作对照。结果前列腺癌组织中整合素αvβ3和VEGF的表达上调,与正常组织比较差异具有统计学意义(P<0.01)。整合素αvβ3和VEGF的表达均随着PCa的病理分级、临床分期增加其表达上调(P<0.05),与PCa的病理分化程度呈负相关(P<0.01)。在各术前血清PSA值组中,整合素αvβ3及VEGF表达无统计学差异(P>0.05)。整合素αvβ3与VEGF表达呈正相关(rs=0.220),相关有显著性(P<0.05)。结论整合素αvβ3和VEGF可能在前列腺癌的发生、发展及恶性进展过程中起重要作用。将二者结合分析,有助于判断PCa的恶性程度、转移潜能和预后。

整合素αvβ_3对体外骨肉瘤细胞增殖与侵袭力的影响

目的研究整合素αvβ3在骨肉瘤细胞增殖和侵袭性生长中的作用,为以整合素αvβ3为靶点治疗人骨肉瘤提供实验依据。方法①采用MTT比色法和PCNA免疫组化检测法,观察不同浓度的整合素αvβ3抗体对体外培养的MG-63骨肉瘤细胞增殖的影响;②建立Boyden小室细胞侵袭模型,观察不同浓度的整合素αvβ3抗体对体外培养的骨肉瘤细胞侵袭能力的影响。结果①整合素αvβ3抗体对体外培养的MG-63骨肉瘤细胞的增殖有明显的抑制作用,其作用表现出明显的量效关系(P<0.05);②整合素αvβ3抗体显著降低体外培养的MG-63骨肉瘤细胞的侵袭能力,其作用亦表现出明显的量效关系(P<0.05)。结论整合素αvβ3对骨肉瘤细胞的恶性增殖和侵袭性生长具有促进作用,其为抗整合素αvβ3治疗骨肉瘤提供了实验依据。

Molecular mechanism of endocrine-disruptive effects induced by Bisphenol A:The role of transmembrane G-protein estrogen receptor 1 and integrin αvβ3

Bisphenol A(BPA) is one of the highest volume industrial products worldwide and has been widely used to make various products as the intermediates of polycarbonate plastics and epoxy resins.Inevitably, general population has been widely exposed to BPA due to extensive use of BPAcontaining products. BPA has similar chemical structure with the natural estrogen and has been shown to induce a variety of estrogen-like endocrine effects on organism in vivo or in vitro. High doses of BPA tend to act as antagonist of estrogen receptors(ERs) by directly regulating the genomic transcription. However, BPA at environmentally relevant low-dose always disrupt the biological function via a non-genomic manner mediated by membrane receptors, rather than ERs. Although some studies had investigated the non-genomic effects of low-dose BPA, the exact molecular mechanism still remains unclear. Recently, we found that membrane G protein-coupled estrogen receptor 1 and integrin αvβ3 and its relative signal pathways participate in the induction of male germ cell proliferation and thyroid transcription disruption by the low-dose BPA. A profound understanding for the mechanism of action of the environmentally relevant BPA exposure not only contributes to objectively evaluate and predict the potential influence to human health, but also provides theoretical basis and methodological support for assessing health effects trigged by other estrogen-like environmental endocrine disruptors. Based mainly on our recent findings, this review outlines the research progress of molecular mechanism on endocrine disrupting effects of environmental low-dose BPA, existing problems and some consideration for future studies.

输卵管积水治疗前后彩色多普勒超声血流变化与整合素αvβ_3关系研究进展

输卵管积水是一种很常见的妇科疾病,是导致女性不孕常见的原因之一。据不完全统计,在寻求体外受精-胚胎移植(IVF-ET)的患者中,约有30%的患者患有输卵管积水。输卵管积水可以间接影响子宫内膜的容受性,其中整合素αvβ3在胚胎着床方面起了非常重要的作用。目前可以通过彩色多普勒超声检查对输卵管积水患者治疗前后子宫内膜容受性进行评价,本文重点介绍输卵管积水治疗前后彩色多普勒超声血流的变化与整合素αvβ3关系的国内外研究进展。

基于改进DeepLabv3+的轻量化作物杂草识别方法

为在存储资源与计算能力有限的设备上实现田间作物和杂草的识别,本文提出一种基于改进DeepLabv3+的轻量化语义分割网络。首先,以MobileNet v2作为DeepLabv3+的特征提取骨干网络,提出双分支残差模块替换倒残差模块,并删除后两层卷积以降低模型参数量。其次,在空洞空间金字塔池化(Atrous Spatial Pyramid Pooling,ASPP)模块中引入分组逐点卷积,使用深度扩张卷积替换标准卷积,并将卷积后的特征图进行多尺度特征融合增强对作物和杂草深层特征的提取能力。最后,将原有的非线性激活函数替换为Leaky ReLU激活函数来提升分割精度。实验结果表明:改进后网络的mIOU达到86.75%,参数量仅为0.69M,FPS达到了98,与原始DeepLabv3+以及3个典型轻量化语义分割网络的相比,参数量最小,在对比的轻量化网络中具有最高的分割精度。

慢性盆腔炎性不孕患者子宫内膜整合素α_vβ_3表达及与甾体激素关系的研究

【目的】研究慢性盆腔炎性不孕患者子宫内膜整合素αvβ3的表达,并分析其体内甾体激素与整合素αvβ3表达的相关性。【方法】选取25例慢性盆腔炎性不孕症患者,同时选择15例具有正常生育能力的育龄妇女,分别设为实验组和对照组,采用流式细胞荧光标记测量技术对子宫内膜中整合素αvβ3的表达进行定量检测。在同期内取血清检测实验组及对照组体内雌孕激素水平,分析甾体激素与子宫内膜整合素αvβ3表达在植入窗口期(种植期)的相关性。【结果】(1)两组黄体中期血清雌二醇(E2)水平及雌二醇/孕酮(E2/P)比值比较均无显著性差异(P>0.05),而血清P水平比较有显著性差异(P<0.05)。(2)两组黄体中期(分泌中期)子宫内膜整合素αvβ3表达比较差异有显著性意义(P<0.05)。(3)雌激素与子宫内膜整合素αvβ3无相关性,而孕激素与整合素αvβ3显示正相关性,孕激素的表达水平越高,整合素αvβ3表达水平相应也越高。【结论】整合素αvβ3在正常育龄妇女子宫内膜种植窗期的表达高于慢性盆腔炎性不孕患者;整合素的表达水平与卵巢分泌的甾体激素孕激素的表达呈一致性,孕激素影响着整合素αvβ3表达的水平。

靶向整合素α_Vβ_3的分子影像探针

整合素αVβ3作为整合素家族中的重要成员,介导了细胞和细胞外基质、细胞和细胞之间的相互黏附,具有调控细胞增殖、分化、细胞形态和迁移等多种功能,在肿瘤血管生成的过程中发挥重要的作用。作为靶向肿瘤的受体,利用核素、核磁共振、超声波和光学等影像技术,结合靶向整合素αVβ3分子成像探针非侵入性的检测整合素αVβ3在肿瘤组织和肿瘤新生血管中的表达,具有潜在的临床应用价值,可用于临床肿瘤诊断和抗肿瘤药物的临床治疗后观察。本文主要针对现有靶向整合素αVβ3的分子探针及其影像技术作一简要综述。