期刊文献+
共找到72篇文章
< 1 2 4 >
每页显示 20 50 100
中药抗肿瘤机制中的11种信号通路 被引量:58
1
作者 洪梓德 莫志贤 《中国实验方剂学杂志》 CAS CSCD 北大核心 2018年第21期205-218,共14页
细胞信号转导是指胞外信号刺激细胞,导致多种信号分子相互转换,最终产生对应的生物学功能的过程。各种细胞内外信号分子通过细胞内的信号转导过程,调节离子通道、代谢酶、转录因子等的活性,而参与了疾病发生、发展的各个方面。随着分子... 细胞信号转导是指胞外信号刺激细胞,导致多种信号分子相互转换,最终产生对应的生物学功能的过程。各种细胞内外信号分子通过细胞内的信号转导过程,调节离子通道、代谢酶、转录因子等的活性,而参与了疾病发生、发展的各个方面。随着分子生物学的进一步发展,各种实验研究逐渐提高大家对肿瘤的发生机制和参与调控肿瘤细胞增殖、分化、血管形成、侵袭、转移的信号通路的认识。细胞内信号通路失调,最终造成细胞增殖与凋亡异常是细胞癌变的主要机制之一,针对这些重要的信号通路的分子靶向治疗可以逆转、延迟、阻止致癌过程。大量临床实践表明,中医药在肿瘤的治疗中已经表现出以下几个方面的疗效优势,减轻放化疗的毒副作用、改善临床症状、提高生存质量、稳定瘤体、术后防治肿瘤转移复发、延长生存期和提高生存率。以往许多实验研究表明,抗肿瘤中药可从多条途径调节细胞信号转导通路,而发挥抗肿瘤作用。本文通过检索相关文献,对近几年有关中药抗肿瘤的相关实验进行归纳,总结出这些抗肿瘤中药研究中所涉及的11种信号通路,以期为后续更进一步的研究提供参考。 展开更多
关键词 中药 抗肿瘤 机制 信号通路 激活 研究进展
原文传递
青光眼睫状体炎综合征患者血液中补体系统活化状态的分析 被引量:9
2
作者 陈文杰 赵军 +2 位作者 祝天辉 彭诗茗 黄晓生 《中华实验眼科杂志》 CAS CSCD 北大核心 2016年第7期645-648,共4页
背景补体系统的活化参与葡萄膜炎和开角型青光眼的病理过程。青光眼睫状体炎综合征(PSS)的发病具有葡萄膜炎和开角型青光眼的病理特点,其具体病因及其与血清补体水平和活化情况的关系鲜见报道。目的检测PSS患者发病时血液中补体活化... 背景补体系统的活化参与葡萄膜炎和开角型青光眼的病理过程。青光眼睫状体炎综合征(PSS)的发病具有葡萄膜炎和开角型青光眼的病理特点,其具体病因及其与血清补体水平和活化情况的关系鲜见报道。目的检测PSS患者发病时血液中补体活化情况,为探讨PSS的发病机制提供依据。方法采用前瞻性病例对照研究方法,纳入2013年12月至2015年12月在深圳市眼科医院确诊的PSS患者79例为PSS组,同期纳入深圳市血液中心健康献血者83名为正常对照组。采用免疫散射比浊法检测2个组受检者血清补体途径中共同的活化成分c3、经典途径及凝集素途径中共同的活化成分C4、IgG、IgM及IgA的质量浓度;采用ELISA双抗夹心法测定各组受检者血清经典途径标志物补体c1q、凝集素途径标志物纤维胶凝蛋白2(FCN2)、替代途径标志物补体Bb因子、3条补体活化途径中的共同活化产物C3a及终末期溶解型膜攻击复合物sC5b一9的质量浓度;同时分析PSS组患者血清C3a与sC5b-9质量浓度变化的关系。结果PSS组患者血清c3、c4、C1q、FCN2、C3a、sC5b-9、IgG、IgM和IgA质量浓度明显高于正常对照组,差异均有统计学意义(Z=-4.743、-2.913、-1.985、-2.620、-2.062、-2.500、-7.010、-6.327、-3.652,均P〈0.05);PSS组患者血清补体Bb因子质量浓度为13.87(9.24,32.00)μg/ml,明显低于正常对照组的20.51(12.90,33.50)μg/ml,差异有统计学意义(Z=-2.515,P=0.012)。PSS组患者血清sC5b-9质量浓度为0.41(0.16,1.32)μg/ml,血清C3a质量浓度为190.3(81.0,541.3)μg/ml,二者变化呈明显正相关(rs=0.832,P〈0.001)。结论PSS患者活动期补体系统活化,可能是通过补体替代途径和/或经典途径及凝集素途径实现的。 展开更多
关键词 开角型青光眼 综合征 睫状体炎 补体活化/生理 补体活化通路/生理
下载PDF
Long-term exposure to genistein inhibits the proliferation of gallbladder cancer by downregulating the MCM complex 被引量:8
3
作者 Yajun Geng Shili Chen +49 位作者 Yang Yang Huijie Miao Xuechuan Li Guoqiang Li Jian Ma TongZhang Tai Ren Yongsheng Li Lin Li Liguo Liu Jiahua Yang Ziyi Wang Lu Zou Ke Liu Yang Li Siyuan Yan Xuya Cui Xuheng Sun Bo Yang Lingxiao Zhang Xusheng Han Chuanlei Wang BoChen Xueliang Yue Wei Liang Jianjun Ren Jianguang Jia Jianfeng Gu Zhizhen Li Tiansuo Zhao Peng Wang Dong Wei Shimei Qiu Dongxi Xiang Xinsen Xu Wei Chen Min He Linhua Yang Hui Wang Tao Chen Rong Hua Xu’an Wang Xiangsong Wu Wei Gong Guangyi Wang Maolan Li Wei Zhang Rong Shao Wenguang Wu Yingbin Liu 《Science Bulletin》 SCIE EI CSCD 2022年第8期813-824,M0003,共13页
Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors.The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystit... Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors.The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystitis transforms into gallbladder cancer(GBC),therefore,it is important to investigate the relationship between long-term exposure to soy isoflavones and the occurrence and progression of GBC.This case-control study(n=85 pairs)found that the high level of plasma soy isoflavoneDgenistein(GEN)was associated with a lower risk of gallbladder cancer(≥326.00 ng/m L compared to≤19.30ng/m L,crude odds ratio 0.15,95%CI 0.04–0.59;P for trend=0.016),and that the level of GEN exposure negatively correlated with Ki67 expression in GBC tissue(n=85).Consistent with these results,the proliferation of GBC cells was inhibited in the long-term exposure models of GEN in vitro and in vivo.The long-term exposure to GEN reduced the tyrosine kinase activity of ERBB2 and impaired the function of the PTK6-AKT-GSK3βaxis,leading to downregulation of the MCM complex in GBC cells.In summary,long-term exposure to GEN associated with soy products intake might play a certain role in preventing GBC and even inhibiting the proliferation of GBC cells. 展开更多
关键词 Gallbladder cancer Dietary exposure GENISTEIN ERBB2 pathway activation MCM protein complex
原文传递
白血病形成中JAK/STAT信号通路的持续激活 被引量:6
4
作者 李英华 罗建民 《国际病理科学与临床杂志》 CAS 2006年第5期398-402,共5页
JAK/STAT通路是细胞因子、生长因子、激素等广泛应用的信号转导通路,白血病形成中普遍存在JAK/STAT通路的持续激活。白血病融合蛋白的表达、酪氨酸激酶过度表达或激活突变及某些病毒感染可导致JAK/STAT通路的持续激活和调节异常,并引起... JAK/STAT通路是细胞因子、生长因子、激素等广泛应用的信号转导通路,白血病形成中普遍存在JAK/STAT通路的持续激活。白血病融合蛋白的表达、酪氨酸激酶过度表达或激活突变及某些病毒感染可导致JAK/STAT通路的持续激活和调节异常,并引起细胞的转化和白血病形成。了解白血病形成中JAK/STAT通路的异常调节有助于开发靶向JAK/STAT通路的治疗策略。 展开更多
关键词 JAK/STAT 信号通路 持续激活 白血病形成
下载PDF
CH_2O与H反应机理的量子化学研究 被引量:7
5
作者 李来才 朱元强 《四川师范大学学报(自然科学版)》 CAS CSCD 北大核心 2005年第2期214-217,共4页
用密度泛函理论(DFT)的B3LYP方法,在6 311++G(3df,3pd)基组水平上研究了CH2O与H自由基反应的微观机理,全参数优化了反应过程中各反应物、中间体、过渡态和产物的几何构型,在CCSD(T)水平上计算了它们的能量.振动分析结果证实了中间体和... 用密度泛函理论(DFT)的B3LYP方法,在6 311++G(3df,3pd)基组水平上研究了CH2O与H自由基反应的微观机理,全参数优化了反应过程中各反应物、中间体、过渡态和产物的几何构型,在CCSD(T)水平上计算了它们的能量.振动分析结果证实了中间体和过渡态的真实性,从对CH2O与H的反应机理的研究结果看,CH2O与H原子反应为3条反应通道多步反应过程,CH2O与H原子反应的主要反应通道是CH2O+H→TS6→CHO+H2,其主要产物是自由基CHO和H2,与实验结果吻合. 展开更多
关键词 反应机理 过渡态 反应通道 活化能
下载PDF
HCO自由基与NO_2反应机理的理论研究 被引量:6
6
作者 朱元强 李来才 《四川师范大学学报(自然科学版)》 CAS CSCD 北大核心 2005年第1期90-93,共4页
用密度泛函理论(DFT)的B3LYP和B3P86方法,在6 311++G(d,p)基组水平上研究了HCO自由基与NO2反应的微观机理,全参数优化了反应过程中各反应物、中间体、过渡态和产物的几何构型.在CBS QB3及G3水平上计算了各驻点的能量.振动分析和IRC计算... 用密度泛函理论(DFT)的B3LYP和B3P86方法,在6 311++G(d,p)基组水平上研究了HCO自由基与NO2反应的微观机理,全参数优化了反应过程中各反应物、中间体、过渡态和产物的几何构型.在CBS QB3及G3水平上计算了各驻点的能量.振动分析和IRC计算结果都证实了中间体和过渡态的真实性.从对HCO自由基与NO2的反应机理的研究结果看,HCO自由基与NO2反应的几条通道控制步骤的活化能分别为112.49和291.49kJ·mol-1,反应HCO+NO2→HONO+CO的活化能较低为主反应通道.理论计算所得的反应产物是HONO,CO2,NO,CO,H,这些产物已被实验手段检测到,这说明以上结论与实验值相吻合,从而证明我们的研究结果是可靠的. 展开更多
关键词 反应机理 过渡态 反应通道 活化能 NO2
下载PDF
脊髓损伤后细胞自噬的调控治疗机制及策略
7
作者 杨溢珂 任亚锋 +4 位作者 李冰 尚文雅 黄靖 郭佳 刘慧瑶 《中国组织工程研究》 CAS 北大核心 2025年第18期3885-3896,共12页
背景:细胞自噬通过自噬体-溶酶体降解途径来维持代谢和体内平衡,其与脊髓损伤后远端神经元细胞死亡和功能恢复受损密切相关,靶向细胞自噬来促进脊髓损伤后功能恢复是比较有前景的治疗方向。目的:对细胞自噬在脊髓损伤中的作用、细胞自... 背景:细胞自噬通过自噬体-溶酶体降解途径来维持代谢和体内平衡,其与脊髓损伤后远端神经元细胞死亡和功能恢复受损密切相关,靶向细胞自噬来促进脊髓损伤后功能恢复是比较有前景的治疗方向。目的:对细胞自噬在脊髓损伤中的作用、细胞自噬的相关调控机制及治疗策略进行归纳总结。方法:以“spinal cord injury,autophagy,regulatory mechanisms,autophagy pathway,therapeutic target”为检索词,检索PubMed数据库;以“脊髓损伤,细胞自噬,调控机制,自噬通路,治疗靶点”为检索词,检索中国知网,最终纳入133篇英文文献和4篇中文文献。结果与结论:①细胞自噬作为细胞程序性死亡方式的一种,在脊髓损伤的进展和治疗中起着至关重要的作用。大多数研究表明,适度激活或促进自噬能够通过减少炎症反应和细胞凋亡来促进神经功能的恢复;少数研究表明,过度激活自噬相反,会阻碍脊髓损伤后的功能恢复。②脊髓损伤后,PI3K/AKT/mTOR、MAPK、AMPK、p53信号通路及Beclin-1、ATG和LC3等因子正向或负向调节细胞自噬的发生发展。③促进或抑制自噬可能是调控创伤性脊髓损伤发病机制的有前景的治疗策略,西药氨氯地平、二甲双胍、米诺环素,中医药山楂叶总黄酮、白桦脂酸、氧化苦参碱、针灸,以及细胞外囊泡、外泌体、活性氧响应的复合纤维等作为细胞自噬的激活剂,通过激活细胞自噬,减轻脊髓损伤的继发性损伤反应;而西药胰岛素样生长因子1、依拉达奉,中医药人参皂苷、针灸,以及水凝胶搭载碱性成纤维细胞生长因子作为细胞自噬的抑制剂,通过抑制过度的细胞自噬来促进脊髓损伤后的功能恢复。④细胞自噬的相关调控因子之间相互联系,而细胞自噬对于脊髓损伤的双向作用使得调控细胞自噬的主导因素尚需进一步探讨。⑤以自噬作为脊髓损伤治疗靶点的研究多在动物模型中进行,� 展开更多
关键词 脊髓损伤 细胞自噬 调控机制 自噬通路 治疗靶点 自噬激活 自噬抑制 组织工程 工程化细胞
Pathogenesis of RON receptor tyrosine kinase in cancer cells: activation mechanism, functional crosstalk, and signaling addiction 被引量:4
8
作者 Ming-Hai Wang Ruiwen Zhang +1 位作者 Yong-Qing Zhou Hang-Ping Yao 《The Journal of Biomedical Research》 CAS 2013年第5期345-356,共12页
The RON receptor tyrosine kinase, a member of the MET proto-oncogene family, is a pathogenic factor im- plicated in tumor malignancy. Specifically, aberrations in RON signaling result in increased cancer cell growth, ... The RON receptor tyrosine kinase, a member of the MET proto-oncogene family, is a pathogenic factor im- plicated in tumor malignancy. Specifically, aberrations in RON signaling result in increased cancer cell growth, survival, invasion, angiogenesis, and drug resistance. Biochemical events such as ligand binding, receptor over- expression, generation of structure-defected variants, and point mutations in the kinase domain contribute to RON signaling activation. Recently, functional crosstalk between RON and signaling proteins such as MET and EFGR has emerged as an additional mechanism for RON activation, which is critical for tumorigenic develop- ment. The RON signaling crosstalk acts either as a regulatory feedback loop that strengthens or enhances tumor- igenic phenotype of cancer cells or serves as a signaling compensatory pathway providing a growth/survival ad- vantage for cancer cells to escape targeted therapy. Moreover, viral oncoproteins derived from Friend leukemia or Epstein-Barr viruses interact with RON to drive viral oncogenesis. In cancer cells, RON signaling is integrated into cellular signaling network essential for cancer cell growth and survival. These activities provide the mo- lecular basis of targeting RON for cancer treatment. In this review, we will discuss recent data that uncover the mechanisms of RON activation in cancer cells, review evidence of RON signaling crosstalk relevant to cancer malignancy, and emphasize the significance of the RON signaling addiction by cancer cells for tumor therapy. Understanding aberrant RON signaling will not only provide insight into the mechanisms of tumor pathogenesis, but also lead to the development of novel strategies for molecularly targeted cancer treatment. 展开更多
关键词 Receptor tyrosine kinase (RON) signaling pathway activation mechanism signaling crosstalk on-cogene addiction TUMORIGENESIS
下载PDF
Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections 被引量:1
9
作者 Dongdong Xu Jun Hu +8 位作者 Jiawei Mei Jun Zhou Zhengxi Wang Xudong Zhang Quan Liu Zheng Su Wanbo Zhu Hongjian Liu Chen Zhu 《Bioactive Materials》 SCIE CSCD 2024年第5期82-98,共17页
Repetitive implant-related infections(IRIs)are devastating complications in orthopedic surgery,threatening implant survival and even the life of the host.Biofilms conceal bacterial-associated antigens(BAAs)and result ... Repetitive implant-related infections(IRIs)are devastating complications in orthopedic surgery,threatening implant survival and even the life of the host.Biofilms conceal bacterial-associated antigens(BAAs)and result in a"cold tumor"-like immune silent microenvironment,allowing the persistence of IRIs.To address this challenge,an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum(CFCP)was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response.Specifically,enhanced sonodynamic therapy(SDT)from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA(dsDNA).Immunogenic dsDNA promoted dendritic cell(DC)maturation through activation of the stimulator of interferon gene(STING)and amplified the immune stimulation of neutrophils via interferon-β(IFN-β).At the same time,enhanced BAA presentation aroused humoral immunity in B and T cells,creating long-term resistance to repetitive infections.Encouragingly,CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention. 展开更多
关键词 Implant-related infections Systemic immunotherapy cGAS-STING pathway Interferon Neutrophil activation
原文传递
Bax/Bak蛋白在凋亡通路中的调控与激活机制 被引量:5
10
作者 王江 魏晓丽 +4 位作者 张爱华 范宗宪 詹俊杰 牟基伟 杨琳红 《生命的化学》 CAS CSCD 2017年第6期952-957,共6页
细胞凋亡是机体维持组织稳态和胚胎发育的重要机制之一,受到多种信号分子的严格调控。促凋亡Bcl-2家族蛋白成员Bax和Bak蛋白在细胞凋亡中扮演着非常重要的角色。在凋亡信号的刺激下,Bax和Bak蛋白被激活并在线粒体上互相凝集成簇,使得线... 细胞凋亡是机体维持组织稳态和胚胎发育的重要机制之一,受到多种信号分子的严格调控。促凋亡Bcl-2家族蛋白成员Bax和Bak蛋白在细胞凋亡中扮演着非常重要的角色。在凋亡信号的刺激下,Bax和Bak蛋白被激活并在线粒体上互相凝集成簇,使得线粒体膜的通透性增加,引起凋亡因子的释放,并最终诱导细胞的死亡。本文主要介绍Bax和Bak蛋白在细胞凋亡过程中的调控与激活机制,并详细阐述目前它们在线粒体凋亡通路中的几个激活模型,总结二者在激活线粒体凋亡通路中的作用,为进一步研究线粒体凋亡通路作一铺垫。 展开更多
关键词 BAX BAK 凋亡通路 激活 调控
原文传递
HCO自由基与HO_2自由基反应机理的理论研究 被引量:4
11
作者 刘俊伶 朱元强 李来才 《四川师范大学学报(自然科学版)》 CAS CSCD 北大核心 2006年第6期726-731,共6页
用密度泛函理论(DFT)的B3LYP方法,在6-311++G(d,p)基组水平下研究了HCO自由基与HO2自由基反应的微观机理,全参数优化了反应过程中各反应物、中间体、过渡态和产物的几何构型,在G3水平上计算了各反应驻点的能量.振动分析和内禀反应坐标(I... 用密度泛函理论(DFT)的B3LYP方法,在6-311++G(d,p)基组水平下研究了HCO自由基与HO2自由基反应的微观机理,全参数优化了反应过程中各反应物、中间体、过渡态和产物的几何构型,在G3水平上计算了各反应驻点的能量.振动分析和内禀反应坐标(IRC)计算的结果都证实了中间体和过渡态的真实性.研究结果表明,HCO自由基与HO2自由基反应为多通道多步反应过程,其主要通道是生成产物HCHO与O2的反应途径. 展开更多
关键词 反应机理 过渡态 反应通道 活化能 HO2
下载PDF
核转录因子κB活化途径干预对肝细胞癌变的影响 被引量:2
12
作者 于洪波 姚登福 《中国临床药理学与治疗学》 CAS CSCD 2008年第2期228-233,共6页
肝癌发生是一多中心、多病因、多阶段的发展过程。本文对NF-κB活化途径干预与肝细胞癌变关系的研究进展进行简单的综述。NF-κB的过度表达参与了肝癌的发生、发展。NF-κB表达的进行性增加,可反映肝细胞的早期癌变。而抑制NF-κB的活... 肝癌发生是一多中心、多病因、多阶段的发展过程。本文对NF-κB活化途径干预与肝细胞癌变关系的研究进展进行简单的综述。NF-κB的过度表达参与了肝癌的发生、发展。NF-κB表达的进行性增加,可反映肝细胞的早期癌变。而抑制NF-κB的活性可干预肝细胞恶性转化过程,可能成为肝癌治疗的新方向。 展开更多
关键词 NF—kB 肝癌 信号通路 活化途径 干预
下载PDF
STING-activating dendritic cell-targeted nanovaccines that evoke potent antigen cross-presentation for cancer immunotherapy
13
作者 Nguyen Thi Nguyen Xuan Thien Le +5 位作者 Woo Tak Lee Yong Taik Lim Kyung Taek Oh Eun Seong Lee Han-Gon Choi Yu Seok Youn 《Bioactive Materials》 SCIE CSCD 2024年第12期345-365,共21页
Recently,nanovaccine-based immunotherapy has been robustly investigated due to its potential in governing the immune response and generating long-term protective immunity.However,the presentation of a tumor peptide-ma... Recently,nanovaccine-based immunotherapy has been robustly investigated due to its potential in governing the immune response and generating long-term protective immunity.However,the presentation of a tumor peptide-major histocompatibility complex to T lymphocytes is still a challenge that needs to be addressed for eliciting potent antitumor immunity.Type 1 conventional dendritic cell(cDC1)subset is of particular interest due to its pivotal contribution in the cross-presentation of exogenous antigens to CD8+T cells.Here,the DC-derived nanovaccine(denoted as Si9GM)selectively targets cDC1s with marginal loss of premature antigen release for effective stimulator of interferon genes(STING)-mediated antigen cross-presentation.Bone marrow dendritic cell(BMDC)-derived membranes,conjugated to cDC1-specific antibody(αCLEC9A)and binding to tumor peptide(OVA257-264),are coated onto dendrimer-like polyethylenimine(PEI)-grafted silica nanoparticles.Distinct molecular weight-cargos(αCLEC9A-OVA257-264 conjugates and 2′3′-cGAMP STING agonists)are loaded in hierarchical center-radial pores that enables lysosome escape for potent antigen-cross presentation and activates interferon type I,respectively.Impressively,Si9GM vaccination leads to the upregulation of cytotoxic T cells,a reduction in tumor regulatory T cells(Tregs),M1/M2 macrophage polarization,and immune response that synergizes with αPD-1 immune checkpoint blockade.This nanovaccine fulfills a dual role for both direct T cell activation as an artificial antigen-presenting cell and DC subset maturation,indicating its utility in clinical therapy and precision medicine. 展开更多
关键词 DC-based nanovaccines Artificial antigen-presenting cells Type 1 conventional dendritic cells STING pathway activation Antigen cross-presentation
原文传递
Macrophages-mediated tumor accumulation and deep penetration of bismuth/manganese biomineralized nanoparticles for enhanced radiotherapy
14
作者 Jiahao Liu Peng Liu +9 位作者 Junhong Duan Qiongxuan Xie Jie Feng Hongpei Tan Ze Mi Ying Li Yunjie Liao Pengfei Rong Wenhu Zhou Xiang Gao 《Chinese Chemical Letters》 SCIE CAS CSCD 2024年第12期198-205,共8页
Radiotherapy(RT)is a widely used cancer treatment,and the use of metal-based nano-radiotherapy sensitizers has shown promise in enhancing its efficacy.However,efficient accumulation and deep penetration of these sensi... Radiotherapy(RT)is a widely used cancer treatment,and the use of metal-based nano-radiotherapy sensitizers has shown promise in enhancing its efficacy.However,efficient accumulation and deep penetration of these sensitizers within tumors remain challenging.In this study,we present the development of bismuth/manganese biomineralized nanoparticles(Bi Mn/BSA)with multiple radiosensitizing mechanisms,including high atomic number element-mediated radiation capture,catalase-mimic oxygenation,and activation of the stimulator of interferon genes(STING)pathway.Significantly,we demonstrate that low-dose RT induces the recruitment of macrophages and subsequent upregulation of Matrix metalloproteinases(MMP)-2 and MMP-9 that degrade the extracellular matrix(ECM).This dynamic process facilitates the targeted delivery and deep penetration of Bi Mn/BSA nanoparticles within tumors,thereby enhancing the effectiveness of RT.By combining low-dose RT with Bi Mn/BSA nanoparticles,we achieved complete suppression of tumor growth in mice with excellent biocompatibility.This study provides a novel and clinically relevant strategy for targeted nanoparticle delivery to tumors,and establishes a safe and effective sequential radiotherapy approach for cancer treatment.These findings hold great promise for improving the outcomes of RT and advancing the field of nanomedicine in cancer therapy. 展开更多
关键词 Radiotherapy sensitizers Metal-based nanoparticles Targeted nanoparticle delivery STING pathway activation Sequential radiotherapy
原文传递
维奈克拉治疗急性髓系白血病的耐药机制及应对策略
15
作者 滕喆 杨新宇 《中南药学》 CAS 2024年第5期1291-1299,共9页
急性髓系白血病(AML)是一类克隆性造血干细胞恶性肿瘤,治疗手段有限,死亡率高,但是近些年涌现多种靶向药物有望改善这一困境。2018年经FDA批准的维奈克拉(Venetoclax)极大地提高了AML患者的应答率。Venetoclax是一种BH3模拟物,它特异性... 急性髓系白血病(AML)是一类克隆性造血干细胞恶性肿瘤,治疗手段有限,死亡率高,但是近些年涌现多种靶向药物有望改善这一困境。2018年经FDA批准的维奈克拉(Venetoclax)极大地提高了AML患者的应答率。Venetoclax是一种BH3模拟物,它特异性地抑制抗凋亡蛋白BCL-2,进而杀伤肿瘤细胞。然而,随着Venetoclax在AML中的广泛应用,其耐药问题逐渐显现。具体的耐药机制主要表现在肿瘤细胞中靶点蛋白BCL-2下调及其他非BCL-2抗凋亡蛋白上调、BCL-2家族中促凋亡蛋白下调及非依赖BCL-2家族蛋白的其他耐药机制。本综述将系统地阐述AML中Venetoclax耐药的分子机制,并总结靶向这些耐药机制的相关治疗策略的新进展。 展开更多
关键词 维奈克拉 耐药 BCL-2蛋白家族 氧化磷酸化 通路激活 线粒体
下载PDF
Toll-like receptor 2-mediated NF-kappa B pathway activation in ocular surface epithelial cells 被引量:4
16
作者 Aihua Hou Min Qi Tin Louis Tong 《Eye and Vision》 SCIE 2017年第1期93-99,共7页
Background:Gram-positive bacteria stimulate Toll-like receptor(TLR)2 and then activate the pro-inflammatory nuclear factor-kappa B(NF-κB)pathway.As the human ocular surface is heavily colonised by gram-positive cocci... Background:Gram-positive bacteria stimulate Toll-like receptor(TLR)2 and then activate the pro-inflammatory nuclear factor-kappa B(NF-κB)pathway.As the human ocular surface is heavily colonised by gram-positive cocci bacteria,a balance of activation/repression of NF-κB target genes is essential to avoid uncontrolled infection or autoimmune-related inflammation.It is advantageous to test NF-κB targeting molecules in an ocular surface culture system that allows assessment of temporal NF-κB activation in a longitudinal fashion without destruction of cells.Such initial testing under standardised conditions should reduce the number of molecules that progress to further evaluation in animal models.This study aims to establish an in-vitro cell culture system to assess NF-κB activation in the context of ocular surface cells.Methods:NF-κB activity was evaluated through a secretory alkaline phosphatase reporter assay(SEAP).Immunoblots and immunofluorescence were used to examine IκBαphosphorylation and p65/p50 nuclear localization.Monocyte chemoattractant protein-1(MCP-1)transcripts were evaluated by real time PCR and protein levels were measured by ELISA.Results:NF-κB activity in HCE-T cells treated with TLR2 activator Pam3CSK4 was higher than control cells at both 6 and 24 h.Pam3CSK4-stimulated NF-κB activation was inhibited by IκK inhibitors,Wedelolactone and BMS-345541.In Pam3CSK4 treated cells,active NF-κB subunits p50 and p65 increased in cell nuclear fractions as early as 1.5 h.Although the level of total IκB-αremained constant,phospho-IκB-αincreased with treatment over time.In the culture media of Pam3CSK4-stimulated cells,MCP-1 protein level was increased,which was suppressed in the presence of IκK inhibitors.Conclusion:NF-κB pathway can be activated by the TLR2 ligand and inhibited by IκK inhibitors in the ocular surface cell culture system.This cell culture system may be used to evaluate TLR-related innate defences in ocular surface diseases. 展开更多
关键词 TLR2 NF-κB pathway activation Ocular surface cells
原文传递
百脉根结瘤信号通道蛋白NSP1和NSP2的转录激活作用 被引量:4
17
作者 储晓洁 康恒 +1 位作者 胡晓晶 张忠明 《华中农业大学学报》 CAS CSCD 北大核心 2010年第5期582-587,共6页
共生结瘤过程是根瘤菌与宿主植物交换信号分子的相互作用过程,结瘤信号通道蛋白基因NSP1和NSP2是结瘤因子诱导的共生信号转导途径的必要元件。LjNSP1和LjNSP2蛋白都包含植物所特有的GRAS结构域,推测为转录调节子,但缺乏明确的生化证据... 共生结瘤过程是根瘤菌与宿主植物交换信号分子的相互作用过程,结瘤信号通道蛋白基因NSP1和NSP2是结瘤因子诱导的共生信号转导途径的必要元件。LjNSP1和LjNSP2蛋白都包含植物所特有的GRAS结构域,推测为转录调节子,但缺乏明确的生化证据。为验证这一推测,本研究采用酵母双杂交系统,将两者分别融合到酵母GAL4转录因子的DNA结合结构域上,根据是否能激活报告基因的表达来验证它们的转录激活能力。结果表明LjNSP1和LjNSP2在酵母体内均具有转录激活的能力。为进一步确定转录激活的区域,对LjNSP1和LjNSP2构建了一系列的缺失突变,鉴别出转录激活区段均位于两者的N-末端的可变区域。为验证作为转录因子的LjNSP1和LjNSP2是否具有结合某种特定基因的启动子的能力,进行了酵母单杂交实验。其结果表明,LjNSP1和LjNSP2蛋白均能够结合根瘤起始基因NIN的启动子,但不能结合钙离子结合蛋白基因CBP1的启动子。 展开更多
关键词 百脉根 共生信号转导 转录激活 GRAS蛋白 酵母单杂交
下载PDF
补体系统在血栓性微血管病中的作用及研究进展 被引量:4
18
作者 曹辉 吴俊 赵育婧 《中华检验医学杂志》 CAS CSCD 北大核心 2019年第12期998-1001,共4页
血栓性微血管病(TMA),是一组具有共同病理特征的急性临床病理综合征,主要包括溶血尿毒综合征(HUS)和血栓性血小板减少性紫癜(TTP),两者在病因和临床表现方面有很多相似之处。补体旁路途径异常活化在HUS的发生发展过程中的作用已经得到... 血栓性微血管病(TMA),是一组具有共同病理特征的急性临床病理综合征,主要包括溶血尿毒综合征(HUS)和血栓性血小板减少性紫癜(TTP),两者在病因和临床表现方面有很多相似之处。补体旁路途径异常活化在HUS的发生发展过程中的作用已经得到公认。研究发现超过100多种补体调节因子或补体本身基因突变与HUS的发生有关,基因突变使得补体负性调节蛋白活性降低或补体激活蛋白功能增强,补体系统异常活化促使内皮损伤及血栓形成。血管性血友病因子裂解酶(ADAMTS)13活性缺失(<10%)是TTP最重要的发病机制,但越来越多的证据提示各种原因诱发补体旁路途径调节失控、过度激活参与了TTP的发生。目前寻找特异性的补体活化生物标志物对患有各种形式TMA的患者进行全面的补充检査,并开发针对该疾病新的靶向治疗药物,是目前国内外对TM A的研究热点。 展开更多
关键词 血栓性微血管病 补体途径 旁路 补体激活 补体系统蛋白质类 生物标记
原文传递
MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis 被引量:2
19
作者 Chao Hou Dong Wang +16 位作者 Mingxia Zhao Petek Ballar Xinru Zhang Qiong Mei Wei Wang Xiang Li Qiang Sheng Jun Liu Chuansheng Wei Yujun Shen Yi Yang Peng Wang Juntang Shao Sa Xu Fuyan Wang Yang Sun Yuxian Shen 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第10期4234-4252,共19页
The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic li... The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment. 展开更多
关键词 Hepatic fibrosis Mesencephalic astrocyte-derived neurotrophic factor Macrophage differentiation Ly6C^(high)macrophages S100A8/S100A9 TLR4 NF-κB pathway HSCs activation
原文传递
Activated complement classical pathway in a murine model of oxygen-induced retinopathy 被引量:1
20
作者 Xue-Ying Tao Shi-Jie Zheng Bo Lei 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2015年第1期17-22,共6页
AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was i... AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR. 展开更多
关键词 oxygen-induced retinopathy complement activation classical pathway RETINA MOUSE
下载PDF
上一页 1 2 4 下一页 到第
使用帮助 返回顶部