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皮肤基底细胞癌中TBX1的表达及其调控细胞增殖的生物学机制
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作者 时永强 范治强 +1 位作者 李文超 赵云超 《临床皮肤科杂志》 北大核心 2025年第6期331-337,共7页
目的:研究皮肤基底细胞癌(BBC)T盒转录因子(TBX)1的表达及其调控细胞增殖的生物学机制。方法:选取手术切除的皮肤BCC组织和正常皮肤组织,检测TBX1的mRNA和蛋白相对表达水平。培养BCC细胞株TE354T,分组并分别转染阴性对照(NC)小干扰RNA(s... 目的:研究皮肤基底细胞癌(BBC)T盒转录因子(TBX)1的表达及其调控细胞增殖的生物学机制。方法:选取手术切除的皮肤BCC组织和正常皮肤组织,检测TBX1的mRNA和蛋白相对表达水平。培养BCC细胞株TE354T,分组并分别转染阴性对照(NC)小干扰RNA(siRNA)、TBX1 siRNA、空白载体、Sonic hedgehog(Shh)过表达载体及Gli家族锌指(Gli)2过表达载体,用不同浓度(1μmol/L、5μmol/L、10μmol/L)Shh抑制剂、不同浓度(5μmol/L、10μmol/L、20μmol/L)Gli2抑制剂处理,检测细胞增殖的吸光度(A)、凋亡率及TBX1、Shh、Gli1、Gli2的mRNA和蛋白水平。结果:皮肤BCC组织中TBX1的mRNA表达水平和蛋白水平均高于正常皮肤组织(P<0.05);与si-NC组比较,si-TBX1组TE354T细胞24 h、48 h、72 h的A值及细胞中TBX1、Shh、Gli2的表达水平降低(P<0.05),细胞凋亡率增加(P<0.05),Gli1的表达水平差异无统计学意义(P>0.05);不同浓度Shh抑制剂组、Gli2抑制剂组TE354T细胞24 h、48 h、72 h的A均显著降低(P<0.05);与si-TBX1+空白质粒组比较,si-TBX1+Shh质粒组和si-TBX1+Gli2质粒组TE354T细胞24 h、48 h、72 h的A值均增加,细胞凋亡率降低(P<0.05)。结论:皮肤BCC中TBX1表达增加,敲低TBX1通过抑制Shh/Gli2通路抑制皮肤BCC细胞株TE354增殖。 展开更多
关键词 皮肤基底细胞癌 T盒转录因子1 Sonic hedgehog Gli家族锌指2 细胞增殖
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LPS致PMVECs损伤时CPNE1/CAV-1相互作用机制研究
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作者 吴翔晖 李琪琪 +5 位作者 李帅 陆宗庆 方普 庞晴晴 汪博 尤青海 《临床肺科杂志》 2025年第5期692-698,共7页
目的探讨脂多糖(LPS)刺激肺微血管内皮细胞(PMVECs)时Copine1(CPNE1)与小窝蛋白-1(CAV-1)的相互作用及SHH信号通路对其调控作用。方法体外培养PMVECs,Western Blot(WB)检测LPS刺激时CPNE1、CAV-1和GLI1表达变化,随机分为LPS时效组(LPS 1... 目的探讨脂多糖(LPS)刺激肺微血管内皮细胞(PMVECs)时Copine1(CPNE1)与小窝蛋白-1(CAV-1)的相互作用及SHH信号通路对其调控作用。方法体外培养PMVECs,Western Blot(WB)检测LPS刺激时CPNE1、CAV-1和GLI1表达变化,随机分为LPS时效组(LPS 10mg/L,0、3、6、12、18、24h)和量效组(0、1、5、10、20、40mg/L);siRNA沉默CPNE1,WB和免疫荧光检测沉默CPNE1后PMVECs表达CAV-1变化,随机分为Control组、LPS组、siCPNE1组、siCPNE1+LPS组;10mg/L LPS刺激PMVEC时给予SHH信号通路抑制剂(Vismodegib)干扰,随机分为Control组、LPS组、Vismodegib组、Vismodegib+LPS组;siRNA沉默CPNE1后给予SHH信号通路激动剂(SAG)干扰,分为Control组、si-CPNE1组、SAG组、si-CPNE1+SAG组。结果(1)LPS刺激PMVECs12h后,与0h组比较,CPNE1、CAV-1和GLI1蛋白的表达均显著增加(P<0.05)。(2)共聚焦免疫荧光技术显示LPS刺激PMVECs时CAV-1和CPNE1的荧光信号增强;与Control组比较,si-CPNE1组的荧光信号降低;与LPS组比较,si-CPNE1+LPS组的荧光信号降低。WB检测提示与LPS组比较,siCPNE1+LPS组CAV-1蛋白表达显著下降(P<0.05)。(3)Vismodegib显著下调LPS诱导增加的GLI1、CPNE1和CAV-1蛋白表达水平(P<0.05);SAG显著上调CPNE1、CAV-1和GLI1蛋白表达水平(P<0.05);沉默CPNE1后给予SAG干扰,CAV-1和CPNE1蛋白表达水平并未出现显著上升(P>0.05)。结论LPS刺激时CPNE1与CAV-1在PMVECs中协同响应,且均受SHH信号通路调控。 展开更多
关键词 脂多糖 肺微血管内皮细胞 Copine1 小窝蛋白-1 Sonic Hedgehog信号通路
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SHH信号转导途径与心肌梗死后血管再生的研究进展
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作者 李龙 国伟 《心血管病学进展》 2025年第10期912-916,共5页
Sonic Hedgehog(SHH)信号转导途径,作为调控胚胎发育和组织稳态的重要途径,近年来被发现通过多种机制参与心肌梗死后血管的再生过程。本文系统性地回顾了SHH通路的核心分子机制及其在血管再生中的作用。这些发现为未来针对心肌梗死后血... Sonic Hedgehog(SHH)信号转导途径,作为调控胚胎发育和组织稳态的重要途径,近年来被发现通过多种机制参与心肌梗死后血管的再生过程。本文系统性地回顾了SHH通路的核心分子机制及其在血管再生中的作用。这些发现为未来针对心肌梗死后血管再生的精准干预提供了潜在的靶点。 展开更多
关键词 心肌梗死 Sonic Hedgehog信号转导途径 血管再生
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Innovative dispersion techniques of graphene nanoplatelets(GNPs)through mechanical stirring and ultrasonication:Impact on morphological,mechanical,and thermal properties of epoxy nanocomposites
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作者 Vasi Uddin Siddiqui S.M.Sapuan Mohd Roshdi Hassan 《Defence Technology(防务技术)》 2025年第1期13-25,共13页
Graphene nanoplatelets(GNPs)have attracted tremendous interest due to their unique properties and bonding capabilities.This study focuses on the effect of GNP dispersion on the mechanical,thermal,and morphological beh... Graphene nanoplatelets(GNPs)have attracted tremendous interest due to their unique properties and bonding capabilities.This study focuses on the effect of GNP dispersion on the mechanical,thermal,and morphological behavior of GNP/epoxy nanocomposites.This study aims to understand how the dispersion of GNPs affects the properties of epoxy nanocomposite and to identify the best dispersion approach for improving mechanical performance.A solvent mixing technique that includes mechanical stirring and ultrasonication was used for producing the nanocomposites.Fourier transform infrared spectroscopy was used to investigate the interaction between GNPs and the epoxy matrix.The measurements of density and moisture content were used to confirm that GNPs were successfully incorporated into the nanocomposite.The findings showed that GNPs are successfully dispersed in the epoxy matrix by combining mechanical stirring and ultrasonication in a single step,producing well-dispersed nanocomposites with improved mechanical properties.Particularly,the nanocomposites at a low GNP loading of 0.1 wt%,demonstrate superior mechanical strength,as shown by increased tensile properties,including improved Young's modulus(1.86 GPa),strength(57.31 MPa),and elongation at break(4.98).The nanocomposite with 0.25 wt%GNP loading performs better,according to the viscoelastic analysis and flexural properties(113.18 MPa).Except for the nanocomposite with a 0.5 wt%GNP loading,which has a higher thermal breakdown temperature,the thermal characteristics do not significantly alter.The effective dispersion of GNPs in the epoxy matrix and low agglomeration is confirmed by the morphological characterization.The findings help with filler selection and identifying the best dispersion approach,which improves mechanical performance.The effective integration of GNPs and their interaction with the epoxy matrix provides the doorway for additional investigation and the development of sophisticated nanocomposites.In fields like aerospace,automotive,and electronics where higher mechanical performance and functionality are required,GNPs'improved mechanical properties and successful dispersion present exciting potential. 展开更多
关键词 Graphene nanoplatelets Epoxy Nanocomposites Mechanical properties Thermal properties Mechanical stirrer Sonication
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基于HLJCORS的R2Sonic2024多波束测量系统水下测量研究
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作者 马传宁 王明亮 +2 位作者 马少华 张福生 柴志彬 《测绘与空间地理信息》 2025年第S2期8-10,共3页
黑龙江省卫星定位连续运行综合服务系统(简称“HLJCORS”)已广泛应用于陆域各行各业,但应用于水下测量的典型案例较少,如何将HLJCORS应用于水下测量也是亟须探索的方向。本文拟从R2Sonic2024多波束测量系统的原理和案例入手,将HLJCORS... 黑龙江省卫星定位连续运行综合服务系统(简称“HLJCORS”)已广泛应用于陆域各行各业,但应用于水下测量的典型案例较少,如何将HLJCORS应用于水下测量也是亟须探索的方向。本文拟从R2Sonic2024多波束测量系统的原理和案例入手,将HLJCORS提供的高精度定位、授时功能应用于R2Sonic2024多波束测量系统中,进一步提升R2Sonic2024多波束测量系统的测量精度,扩大HLJCORS的服务领域。 展开更多
关键词 HLJCORS R2Sonic2024 高精度定位 授时
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Administration of Porphyromonas gingivalis in pregnant mice enhances glycolysis and histone lactylation/ADAM17 leading to cleft palate in offspring
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作者 Xige Zhao Xiaoyu Zheng +7 位作者 Yijia Wang Jing Chen Xiaotong Wang Xia Peng Dong Yuan Ying Liu Zhiwei Wang Juan Du 《International Journal of Oral Science》 2025年第2期268-284,共17页
Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology i... Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection.A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring.However,the precise relationship remains unclear.In this study,the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P.gingivalis injected intravenously and orally into pregnant mice.We investigated an obvious increasing CP(12.5%)in sonicated P.gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium.Then glycolysis and H4K12 lactylation(H4K12la)were detected to elevate in both mouse embryonic palatal mesenchyme(MEPM)cells and macrophages under P.gingivalis exposure which further promoted the transcription of metallopeptidase domain17(ADAM17),subsequently mediated the shedding of transforming growth factor-beta receptor 1(TGFBR1)in MEPM cells and mer tyrosine kinase(MerTK)in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate,eventually caused abnormalities in palate fusion and ossification.The abnormal efferocytosis also led to a predominance of M1 macrophages,which indirectly inhibited palatal osteogenesis via extracellular vesicles.Furthermore,pharmacological ADAM17 inhibition could ameliorate the abnormality of P.gingivalis-induced abnormal palate development.Therefore,our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP. 展开更多
关键词 Pregnant Mice Sonicated Porphyromonas gingivalis Adam Cleft Palate congenital craniofacial defecthas Histone Lactylation periodontal disease GLYCOLYSIS
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Fibrotic scar formation after cerebral ischemic stroke:Targeting the Sonic hedgehog signaling pathway for scar reduction
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作者 Jun Wen Hao Tang +14 位作者 Mingfen Tian Ling Wang Qinghuan Yang Yong Zhao Xuemei Li Yu Ren Jiani Wang Li Zhou Yongjun Tan Haiyun Wu Xinrui Cai Yilin Wang Hui Cao Jianfeng Xu Qin Yang 《Neural Regeneration Research》 2026年第2期756-768,共13页
Recent studies have shown that fibrotic scar formation following cerebral ischemic injury has varying effects depending on the microenvironment.However,little is known about how fibrosis is induced and regulated after... Recent studies have shown that fibrotic scar formation following cerebral ischemic injury has varying effects depending on the microenvironment.However,little is known about how fibrosis is induced and regulated after cerebral ischemic injury.Sonic hedgehog signaling participates in fibrosis in the heart,liver,lung,and kidney.Whether Shh signaling modulates fibrotic scar formation after cerebral ischemic stroke and the underlying mechanisms are unclear.In this study,we found that Sonic Hedgehog expression was upregulated in patients with acute ischemic stroke and in a middle cerebral artery occlusion/reperfusion injury rat model.Both Sonic hedgehog and Mitofusin 2 showed increased expression in the middle cerebral artery occlusion rat model and in vitro fibrosis cell model induced by transforming growth factor-beta 1.Activation of the Sonic hedgehog signaling pathway enhanced the expression of phosphorylated Smad 3 and Mitofusin 2 proteins,promoted the formation of fibrotic scars,protected synapses or promoted synaptogenesis,alleviated neurological deficits following middle cerebral artery occlusion/reperfusion injury,reduced cell apoptosis,facilitated the transformation of meninges fibroblasts into myofibroblasts,and enhanced the proliferation and migration of meninges fibroblasts.The Smad3 phosphorylation inhibitor SIS3 reversed the effects induced by Sonic hedgehog signaling pathway activation.Bioinformatics analysis revealed significant correlations between Sonic hedgehog and Smad3,between Sonic hedgehog and Mitofusin 2,and between Smad3 and Mitofusin 2.These findings suggest that Sonic hedgehog signaling may influence Mitofusin 2 expression by regulating Smad3 phosphorylation,thereby modulating the formation of early fibrotic scars following cerebral ischemic stroke and affecting prognosis.The Sonic Hedgehog signaling pathway may serve as a new therapeutic target for stroke treatment. 展开更多
关键词 central nervous system FIBROBLASTS fibrosis ischemic stroke Mitofusin 2 middle cerebral artery occlusion/reperfusion P-Smad3 Sonic Hedgehog SMAD3 TOM20
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基于Sonic Hedgehog通路探讨EGCG对AD中少突胶质细胞损伤的保护作用和机制研究
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作者 彭欢 孟琳 +3 位作者 胡峰瑞 张颢严 姜超 王杉 《河北医药》 2025年第5期715-720,727,共7页
目的基于Sonic Hedgehog(Shh)通路探讨表没食子儿茶素没食子酸酯(EGCG)对阿尔茨海默病(Alzheimer’s disease,AD)中少突胶质细胞损伤的保护作用,并阐明相关机制。方法构建过表达人淀粉样前体蛋白(h-APP)和早老蛋白1(h-PSEN1)的稳转小鼠... 目的基于Sonic Hedgehog(Shh)通路探讨表没食子儿茶素没食子酸酯(EGCG)对阿尔茨海默病(Alzheimer’s disease,AD)中少突胶质细胞损伤的保护作用,并阐明相关机制。方法构建过表达人淀粉样前体蛋白(h-APP)和早老蛋白1(h-PSEN1)的稳转小鼠海马神经元细胞系HT22(HT22-AD),并收集HT22-AD上清加入少突胶质细胞系OLN-93细胞,检测APP和PSEN1失调对少突胶质细胞的影响。用EGCG处理HT22-AD细胞,进一步收集该上清加入OLN-93细胞中,观察EGCG处理后的HT22-AD细胞上清对OLN-93细胞损伤的影响。结果HT22-AD细胞中Shh通路中Shh配体表达水平升高(P<0.05)。OLN-93细胞在HT22-AD细胞上清作用后发现细胞突起萎缩;Shh通路下游分子Sufu水平降低,Gli1水平升高(P<0.05);细胞骨架相关分子Rho相关激酶2(Rock2)水平升高(P<0.05);凋亡相关蛋白Bcl-2水平降低,Bax水平升高(P<0.05)。HT22-AD细胞中Shh表达水平降低(P<0.05)。OLN-93细胞在加入EGCG处理的HT22-AD细胞上清后发现:与未加入EGCG的模型组相比,EGCG给药组细胞突起伸长,Sufu、Bcl-2表达水平升高,Gli1、Rock2、Bax蛋白表达水平降低(P<0.05)。结论EGCG对HT22-AD细胞模型引起的OLN-93细胞突起萎缩和凋亡损伤具有保护作用,机制与Shh通路的下调有关。 展开更多
关键词 阿尔茨海默病 EGCG OLN-93细胞 HT22细胞 Sonic Hedgehog信号通路
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小型猪乳磨牙胚SHH的时空表达 被引量:1
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作者 高振华 王凌霄 +1 位作者 王莹鑫 石媛媛 《北京口腔医学》 CAS 2024年第3期159-163,共5页
目的本研究通过探索SHH在小型猪第三乳磨牙胚的帽状期、钟状期和分泌期的时空表达情况,拟阐明SHH在牙齿发育调控中的作用。方法收集小型孕猪第三乳磨牙胚,通过原位杂交、免疫组化和实时聚合酶链反应检测SHH的m RNA和蛋白表达水平。结果... 目的本研究通过探索SHH在小型猪第三乳磨牙胚的帽状期、钟状期和分泌期的时空表达情况,拟阐明SHH在牙齿发育调控中的作用。方法收集小型孕猪第三乳磨牙胚,通过原位杂交、免疫组化和实时聚合酶链反应检测SHH的m RNA和蛋白表达水平。结果原位杂交及免疫组化可见SHH在帽状期少量表达于成釉器,但在釉结部位表达较强。在钟状期,SHH在间充质中表达明显增强;在分泌期,SHH在间充质和成釉器中都有所表达,尤其在成牙本质细胞和内釉上皮细胞中表达增强。PCR结果显示,在钟状期,SHH在上皮中表达较多,而在帽状期和分泌期,SHH在上皮和间充质中的表达未见明显统计学差异。结论SHH可能在调节上皮形态发育方面具有重要功能,参与调节信号级联,介导上皮和间充质之间的相互作用,本研究进一步完善了小型猪牙齿发育的信号分子网络。 展开更多
关键词 Sonic Hedgehog 小型猪 牙齿发育 原位杂交 免疫组织化学
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基于行为树的组网服务管控架构及调度方法 被引量:1
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作者 宋睿涛 高先明 +3 位作者 黄姣蕊 杨春刚 黄韬 李芫芫 《系统工程与电子技术》 EI CSCD 北大核心 2024年第10期3547-3556,共10页
传统互联网为实现端到端安全、可靠、实时的网络业务保障,需要在网元节点部署多类组网服务。然而,现有大多数网络设备只提供网络接入和路由等服务功能,缺乏安全、可靠、实时的服务设计。基于开源网络操作系统(software for open network... 传统互联网为实现端到端安全、可靠、实时的网络业务保障,需要在网元节点部署多类组网服务。然而,现有大多数网络设备只提供网络接入和路由等服务功能,缺乏安全、可靠、实时的服务设计。基于开源网络操作系统(software for open networking in the cloud,SONiC)、容器技术和行为树设计一种组网服务管控架构及调度方法,实现面向网络业务保障的组网服务部署,将组网服务部署可编程网络设备进行统一管理和调度,并进行仿真测试。所述组网服务管控架构及调度方法进一步增强了网络设备能力,利用行为树高效协调管控调度过程中的状态转化,保障组网服务的交付质量。 展开更多
关键词 行为树 容器技术 SONiC 组网服务调度
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miR-130a-5p靶向Runx2对牙槽骨成骨细胞增殖和分化的影响及其调控机制研究 被引量:1
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作者 张义林 侯旭 +2 位作者 汪莉 朗么磋 李相宜 《中国美容医学》 CAS 2024年第6期51-55,共5页
目的:探究miR-130a-5p靶向Runt相关转录因子2(Runt-related transcription factor 2,Runx2)对牙槽骨成骨细胞(Alveolar osteoblast,AOB)增殖、凋亡、成骨分化的影响及其机制。方法:将AOB分为NC组、miR-NC组、miR-130a-5p组、miR-130a-5p... 目的:探究miR-130a-5p靶向Runt相关转录因子2(Runt-related transcription factor 2,Runx2)对牙槽骨成骨细胞(Alveolar osteoblast,AOB)增殖、凋亡、成骨分化的影响及其机制。方法:将AOB分为NC组、miR-NC组、miR-130a-5p组、miR-130a-5p+Runx2组和miR-130a-5p+SHH组。双荧光素酶报告验证miR-130a-5p对Runx2、Sonic hedgehog(SHH)的调控关系;CCK-8及EdU染色检测细胞增殖能力;AnnexinV-FITC/PI法检测细胞凋亡能力;ALP染色、茜素红染色检测细胞成骨分化能力;RT-qPCR检测miR-130a-5p、Runx2、SHH、神经胶质瘤关联癌基因同源物1(Gli1)mRNA水平;Western Blot检测增殖细胞核抗原(Proliferating cell nuclear antigen,PCNA)、Ki67、B细胞淋巴瘤/白血病-2(B-cell lymphoma/leukemia-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2 related X protein,Bax)、碱性磷酸酶(Alkaline phosphatase,ALP)、骨钙素(Osteocalcin,OCN)、骨形态发生蛋白2(Bone morphogenetic protein 2,BMP2)、Runx2、SHH、Gil1水平。结果:miR-130a-5p靶向调控Runx2、SHH。过表达miR-130a-5p后,细胞24 h、48 h、72 h OD值及EdU阳性率降低,细胞凋亡率升高,成骨分化能力降低,miR-130a-5p、Bax蛋白水平升高,Runx2、PCNA、Ki67、Bcl-2、ALP、OCN、BMP2蛋白及SHH、Gil1 mRNA和蛋白水平均降低(P<0.05)。过表达miR-130a-5p和Runx2或过表达miR-130a-5p和SHH可减弱过表达miR-130a-5p对细胞增殖、凋亡、成骨分化的影响。结论:miR-130a-5p靶向Runx2抑制AOB增殖和成骨分化,并促进AOB凋亡,其可能通过抑制SHH信号通路发挥作用。 展开更多
关键词 miR-130a-5p Runt相关转录因子2 牙槽骨成骨细胞 Sonic hedgehog信号通路 增殖 分化 调控机制
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The dual role of striatal interneurons:circuit modulation and trophic support for the basal ganglia 被引量:3
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作者 Elliot Wegman Marlena Wosiski-Kuhn Yu Luo 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第6期1277-1283,共7页
Striatal interneurons play a key role in modulating striatal-dependent behaviors,including motor activity and reward and emotional processing.Interneurons not only provide modulation to the basal ganglia circuitry und... Striatal interneurons play a key role in modulating striatal-dependent behaviors,including motor activity and reward and emotional processing.Interneurons not only provide modulation to the basal ganglia circuitry under homeostasis but are also involved in changes to plasticity and adaptation during disease conditions such as Parkinson's or Huntington's disease.This review aims to summarize recent findings regarding the role of striatal cholinergic and GABAergic interneurons in providing circuit modulation to the basal ganglia in both homeostatic and disease conditions.In addition to direct circuit modulation,striatal interneurons have also been shown to provide trophic support to maintain neuron populations in adulthood.We discuss this interesting and novel role of striatal interneurons,with a focus on the maintenance of adult dopaminergic neurons from interneuronderived sonic-hedgehog. 展开更多
关键词 CHOLINERGIC dopamine GABAERGIC INTERNEURON levodopa-induced dyskinesia PARVALBUMIN sonic hedgehog STRIATUM trophic factor
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Hedgehog信号通路在下颌骨发育过程中作用机制的研究进展 被引量:3
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作者 徐谣 李文晋 《口腔疾病防治》 2024年第9期709-714,共6页
下颌骨的发育来源及发育过程均与全身其他骨骼有着显著差异,其发育异常会导致各种骨相关疾病,严重影响了患者的生活质量。近年来Hedgehog信号通路在骨骼发育过程中的作用越来越受到关注。Hedgehog基因包括Sonic Hedgehog(Shh)、Indian H... 下颌骨的发育来源及发育过程均与全身其他骨骼有着显著差异,其发育异常会导致各种骨相关疾病,严重影响了患者的生活质量。近年来Hedgehog信号通路在骨骼发育过程中的作用越来越受到关注。Hedgehog基因包括Sonic Hedgehog(Shh)、Indian Hedgehog(Ihh)和Desert Hedgehog(Dhh)3种亚型,其中Shh及Ihh可通过多种途径参与骨代谢调节,Shh主要参与肢体发育过程,而Ihh主要是在软骨内成骨过程中发挥关键作用。Hedgehog信号通路包括Hedgehog信号蛋白配体、Patched(Ptch)受体、Smoothed(Smo)受体、核内转录因子神经胶质瘤相关癌基因同源蛋白(glioma-associated oncogene homologue,Gli)和下游靶基因等。典型Hedgehog信号通路由Gli激活调控,而非典型Hedgehog信号主要由Ptch、Smo等调控。Shh在早期脊椎动物胚胎形成过程中调控多种生物学行为,如器官的分化、神经干的形成、干细胞的分化增殖、四肢骨骼发育以及牙胚发育等;在骨细胞分化过程中,Shh、Ptch1和Gli1在成骨细胞中均有表达,进一步促进骨髓间充质干细胞向成骨细胞和软骨细胞分化。Ihh对骨骼生长发育以及稳态维持具有不可或缺的功能作用,参与膜内骨领的形成、软骨细胞的增殖和成熟,Ihh在成熟的颅骨成骨细胞中表达,其可作为促成骨因子调控Ptch和骨形态发生蛋白(bone morphogenetic protein,BMP)的表达来诱导膜内骨化过程;脑和肌肉ARNT样蛋白1(brain and muscle ARNT-like 1,BMAL1)可通过与Ptch1和Ihh结合,调节Hedgehog信号通路,在颞下颌关节的软骨形成和软骨内成骨过程中发挥关键作用;而Hedgehog信号激活剂可以改善由BMAL1缺失引起的下颌骨骨量减少。Hedgehog信号失调会对骨发育过程产生重大影响,并导致一系列骨疾病如骨发育异常、骨折、骨质疏松和骨关节炎。然而,Hedgehog信号通路与下颌骨疾病的相关作用机制尚未完全阐明,未来研究可进一步探讨Hedgehog信号作为治疗下颌骨发育相关疾病的潜在靶点。 展开更多
关键词 HEDGEHOG信号通路 下颌骨 髁突 膜内成骨 软骨内成骨 Sonic Hedgehog Indian Hedgehog 作用机制 下颌骨发育异常 颞下颌骨关节炎
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Sonic Hedgehog信号通路参与椎间盘退变的研究进展
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作者 刘永 张海鸿 《中山大学学报(医学科学版)》 CAS CSCD 北大核心 2024年第6期968-975,共8页
随着社会老龄化的加剧,越来越多的患者受到腰背痛的困扰,给患者和社会带来负担。椎间盘退变(IVDD)是导致慢性腰背痛的主要原因,阐明IVDD的致病机制对解决当前所面临的健康问题具有重要意义。近年来,关于Sonic Hedgehog(Shh)通路在IVDD... 随着社会老龄化的加剧,越来越多的患者受到腰背痛的困扰,给患者和社会带来负担。椎间盘退变(IVDD)是导致慢性腰背痛的主要原因,阐明IVDD的致病机制对解决当前所面临的健康问题具有重要意义。近年来,关于Sonic Hedgehog(Shh)通路在IVDD中的研究报道不断出现,Shh信号通路在椎间盘的形成和出生后维持中具有重要作用,并且该通路的表达变化伴随着椎间盘的年龄相关性退行性改变,靶向Shh信号通路可能在IVDD治疗中具有重要意义。本研究对Shh通路在IVDD中的研究进展进行总结,试图探索该信号通路与IVDD的各种已知病理之间的可能联系,并对未来的研究内容进行展望,以期为探究IVDD的有效治疗方式及预防手段提供参考。 展开更多
关键词 椎间盘退变 Sonic Hedgehog 髓核细胞 脊索细胞 胶质瘤相关癌基因同源蛋白
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Gas hydrate saturation from NGHP 02 LWD data in the Mahanadi Basin 被引量:1
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作者 Uma Shankar Pradeep Kumar Yadav +1 位作者 Sneha Devi Udham Singh Yadav 《Energy Geoscience》 EI 2024年第2期279-289,共11页
During the Indian National Gas Hydrate Program(NGHP)Expedition 02,Logging-while-drilling(LWD)logs were acquired at three sites(NGHP-02-11,NGHP-02-12,and NGHP-02-13)across the Mahanadi Basin in area A.We applied rock p... During the Indian National Gas Hydrate Program(NGHP)Expedition 02,Logging-while-drilling(LWD)logs were acquired at three sites(NGHP-02-11,NGHP-02-12,and NGHP-02-13)across the Mahanadi Basin in area A.We applied rock physics theory to available sonic velocity logs to know the distribution of gas hydrate at site NGHP-02-11 and NGHP-02-13.Rock physics modeling using sonic velocity at well location shows that gas hydrate is distributed mainly within the depth intervals of 150-265 m and 100 -215 mbsf at site NGHP-02-11 and NGHP-02-13,respectively,with an average saturation of about 4%of the pore space and the maximum concentration of about 40%of the pore space at 250 m depth at site NGHP-02-11,and at site NGHP-02-13 an average saturation of about 2%of the pore space and the maximum concentration of about 20%of the pore space at 246 m depth,as gas hydrate is distributed mainly within 100-246 mbsf at this site.Saturation of gas hydrate estimated from the electrical resistivity method using density derived porosity and electrical resistivity logs from Archie's empirical formula shows high saturation compared to that from the sonic log.However,estimates of hydrate saturation based on sonic P-wave velocity may differ significantly from that based on resistivity,because gas and hydrate have higher resistivity than conductive pore fluid and sonic P-wave velocity shows strong effect on gas hydrate as a small amount of gas reduces the velocity significantly while increasing velocity due to the presence of hydrate.At site NGHP-02-11,gas hydrate saturation is in the range of 15%e30%,in two zones between 150-180 and 245-265 mbsf.Site NGHP-02-012 shows a gas hydrate saturation of 20%e30%in the zone between 100 and 207 mbsf.Site NGHP-02-13 shows a gas hydrate saturation up to 30%in the zone between 215 and 246 mbsf.Combined observations from rock physics modeling and Archie’s approximation show the gas hydrate concentrations are relatively low(<4%of the pore space)at the sites of the Mahanadi Basin in the turbidite channel system. 展开更多
关键词 Mahanadi Basin Gas hydrate Sonic log Effective medium modeling Electrical resistivity log Archie’s analysis Gas hydrate saturation
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Mechanistic study of the effect of flexible fixation and load-bearing stress environment on fracture healing and shaping 被引量:1
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作者 Xingfu Li Zhenhan Deng Wei Lu 《Animal Models and Experimental Medicine》 CSCD 2024年第6期816-823,共8页
Background:The biomechanical environment created by suture-button fixation Latarjet is conducive to the healing and shaping of the transplanted coracoid,but its mechanism remains unclear.The latest research has found ... Background:The biomechanical environment created by suture-button fixation Latarjet is conducive to the healing and shaping of the transplanted coracoid,but its mechanism remains unclear.The latest research has found that the absence of stem cell chemokine(CXCL12)impeded bone regeneration in Sonic Hedgehog(SHH)-deficient animals.However,whether the biomechanical environment affects SHH and CXCL12 function has not been studied.Methods:Rat fracture models were constructed to simulate stress environments under non-l oad-bearing and load-bearing conditions.The fracture healing and shaping,as well as the expression levels of SHH and CXCL12,were assessed through gross viewing,micro-computed tomography(micro-CT),and histochemical staining.Results:Under flexible fixation,the relative bone volume(BV/TV)of rats exposed to the load-bearing stress environment was significantly higher than that of rats under a non-l oad-bearing stress environment(p≤0.05).Adverse bone shaping was not observed in rats subjected to flexible fixation.The levels of SHH and CXCL12in load-bearing rats exhibited significant elevation(p≤0.05).Under a load-bearing stress environment,no significant difference was observed in the BV/TV between the flexible fixation group and the rigid fixation group(p≥0.05),but there was excessive hyperplasia of the fracture callus in the rigid fixation group.The levels of SHH and CXCL12 in rats subjected to rigid fixation were significantly elevated(p≤0.05).Conclusions:Flexible fixation and load-bearing stress environment may contribute to bone healing and shaping by influencing the levels of SHH and CXCL12,suggested that this mechanism may be relevant to the healing and shaping of the transplanted coracoid after suture-button fixation Latarjet. 展开更多
关键词 CXCL12 flexible fixation sonic hedgehog stress environment
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不同树脂填充对Ⅱ类洞牙体缺损的修复效果及牙周指数和龈沟液炎症因子水平观察 被引量:2
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作者 武浩 杨朝 《现代医学与健康研究电子杂志》 2024年第12期1-3,共3页
目的分析不同树脂填充对Ⅱ类洞牙体缺损的修复效果,并观察患者牙周指数和龈沟液炎症因子水平变化。方法回顾性分析2021年1月至2022年12月徐州管道医院收治的61例Ⅱ类洞牙体缺损患者的临床资料,依据不同的填充材料分为A组(30例,38颗患牙... 目的分析不同树脂填充对Ⅱ类洞牙体缺损的修复效果,并观察患者牙周指数和龈沟液炎症因子水平变化。方法回顾性分析2021年1月至2022年12月徐州管道医院收治的61例Ⅱ类洞牙体缺损患者的临床资料,依据不同的填充材料分为A组(30例,38颗患牙,接受3M Filtek^(TM)Z350纳米复合树脂填充)和B组(31例,39颗患牙,接受SonicFill超声树脂填充)。两组患者修复后均随访12个月。比较两组患者修复效果,修复前和修复后1周牙周指数、龈沟液炎症因子含量,修复后12个月内并发症发生情况。结果B组患者操作时间短于A组(P<0.05),比较修复后3、6、12个月两组患者修复成功率,差异均无统计学意义(均P>0.05);与修复前比,修复后1周两组患者菌斑指数(PI)、出血指数(BI)、牙龈指数(GI)组内及组间比较,差异均无统计学意义(均P>0.05);与修复前比,修复后1周两组患者龈沟液肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、C-反应蛋白(CRP)含量均升高,但组间比较,差异均无统计学意义(均P>0.05);两组患者修复后12个月内并发症总发生率经比较,差异无统计学意义(P>0.05)。结论在Ⅱ类洞牙体缺损患者治疗中,应用Sonic Fill超声树脂填充与应用3M Filtek^(TM)Z350纳米复合树脂填充具有相似的修复效果,且在牙周指数、龈沟液炎症因子水平及并发症方面影响相当,但对于依从性不佳的患者,应用操作时间较短的Sonic Fill超声树脂填充治疗更适用。 展开更多
关键词 牙体缺损 Ⅱ类洞 3M Filtek^(TM)Z350纳米复合树脂 Sonic Fill超声树脂 牙周指数 炎症因子
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Anisotropy measurements and characterization of the Qingshankou shale
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作者 Li Qing-feng Yan Xue-hong +5 位作者 Yan Wei-lin Ren Li Wang Peng Han Jian-qiang Xia Xue Chen Hao 《Applied Geophysics》 SCIE CSCD 2024年第3期468-478,617,共12页
Qingshankou shale(Gulong area,China)exhibits strong acoustic anisotropy characteristics,posing significant challenges to its exploration and development.In this study,the five full elastic constants and multipole resp... Qingshankou shale(Gulong area,China)exhibits strong acoustic anisotropy characteristics,posing significant challenges to its exploration and development.In this study,the five full elastic constants and multipole response law of the Qingshankou shale were studied using experimental measurements.Analyses show that the anisotropy parametersϵandγin the study region are greater than 0.4,whereas the anisotropy parameterδis smaller,generally 0.1.Numerical simulations show that the longitudinal and transverse wave velocities of these strong anisotropic rocks vary significantly with inclination angle,and significant differences in group velocity and phase velocity are also present.Acoustic logging measures the group velocity in dipped boreholes;this differs from the phase velocity to some extent.As the dip angle increases,the longitudinal and SH wave velocities increase accordingly,while the qSV-wave velocity initially increases and then decreases,reaching its maximum value at a dip of approximately 40°.These results provide an effective guide for the correction and modeling of acoustic logging time differences in the region. 展开更多
关键词 Transverse isotropy anisotropy parameter sonic logging group velocity phase velocity
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Effect of Sonic hedgehog gene-modified bone marrow mesenchymal stem cells on graft-induced retinal gliosis and retinal ganglion cells survival in diabetic mice
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作者 Tong Wang Hai-Chun Li +1 位作者 Jin Ma Xi-Ling Yu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第1期34-41,共8页
AIM:To investigate the effects of Sonic hedgehog(Shh)gene-modified bone marrow mesenchymal stem cells(MSCs)on graft-induced retinal gliosis and retinal ganglion cells(RGCs)survival in diabetic mice.METHODS:Bone marrow... AIM:To investigate the effects of Sonic hedgehog(Shh)gene-modified bone marrow mesenchymal stem cells(MSCs)on graft-induced retinal gliosis and retinal ganglion cells(RGCs)survival in diabetic mice.METHODS:Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs(MSC-Shh).Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs(MSC-Gfp;control)were administered in diabetic mice.After 4wk,the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography,and markers of gliosis were examined by immunofluorescence and Western blotting.The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence.The mechanisms underlying the effects of MSC-Shh was investigated.RESULTS:A significant reduction of proliferative vitreoretinopathy(PVR)was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp.Significant downregulation of glial fibrillary acidic protein(GFAP)was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp.The extracellular signal-regulated kinase 1/2(ERK1/2),protein kinase B(AKT)and phosphatidylin-ositol-3-kinase(PI3K)pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp.Brain-derived neurotrophic factor(BDNF)and ciliary neurotrophic factor(CNTF)levels were significantly increased in the host retina,and RGCs loss was significantly prevented after MSC-Shh administration.CONCLUSION:MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice.The ERK1/2,AKT and PI3K pathways are involved in this process.MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice. 展开更多
关键词 mesenchymal stem cells Sonic hedgehog signaling reactive gliosis diabetic retinopathy retinal ganglion cells
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Base Pressure Control with Semi-Circular Ribs at Critical Mach Number
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作者 Ambareen Khan Sher Afghan Khan +2 位作者 Mohammed Nishat Akhtar Abdul Aabid Muneer Baig 《Fluid Dynamics & Materials Processing》 EI 2024年第9期2007-2028,共22页
When better fuel-air mixing in the combustion chamber or a reduction in base drag are required in vehicles,rockets,and aeroplanes,the base pressure control is activated.Controlling the base pressure and drag is necess... When better fuel-air mixing in the combustion chamber or a reduction in base drag are required in vehicles,rockets,and aeroplanes,the base pressure control is activated.Controlling the base pressure and drag is necessary in both scenarios.In this work,semi-circular ribs with varying diameters(2,4,and 6 mm)positioned at six distinct positions(0.5D,1D,1.5D,2D,3D,and 4D)inside a square duct with a side of 15 mm are proposed as an efficient way to apply the passive control technique.In-depth research is done on optimising rib size for various rib sites.According to this study,the base pressure rises as rib height increases.Furthermore,the optimal location for the semi-circular ribs with a diameter of 2 mm is at 0.5D.The 1D location appears to be optimal for the 4 mm size as well.For the 6 mm size,however,the 4D position fills this function. 展开更多
关键词 Base pressure nozzle pressure ratio base drag sonic Mach number passive control
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