搜索到1902篇“ LYSOSOME“的相关文章
Lysosome-targeted carbon dots with a light-controlled nitric oxide releasing property for enhanced photodynamic therapy
2024年
The reactive oxygen species(ROS) generation efficiency is always limited by the extreme tumor microenvironment(TME), leading to unsatisfactory antitumor effects in photodynamic therapy(PDT). As a promising gas therapy molecule, nitric oxide(NO) is independent of oxygen and could even synergize ROS to enhance the therapeutic effect. However, the short half-life, instability, and uncontrollable release of exogenous NO limited the application of tumor synergistic therapy. Herein, we reported a novel kind of red-emissive carbon dots(CDs) that was capable of lysosome-targeted and light-controlled NO delivery. The CDs were synthesized by using metformin and methylene blue(MB) via a hydrothermal method.The obtained metformin-MB CDs(MMCDs) exhibited a higher1O2quantum yield and NO generation efficiency under light emitting diode(LED) light irradiation. Noteworthily, the1O2could further in situ oxidize NO into peroxynitrite anions(ONOO-), which own the higher cytotoxicity against cancer cells.Cell experiments indicate that MMCDs could destruct lysosome membrane integrity and kill almost 80%of Hep G2 cells under light irradiation while very low cytotoxicity in the dark. Moreover, MMCDs significantly decreased tumor volume and weight after phototherapy in hepatoma Hep G2-bearing mice. Our study provides a new strategy for light-controlled NO generation as well as precise lysosome-targeting for enhancement of PDT efficiency.
Hao CaiXiaoyan WuLei JiangFeng YuYuxiang YangYan LiXian ZhangJian LiuZijian LiHong Bi
溶酶体在肾小球疾病中的研究进展
2024年
溶酶体是真核生物中负责降解细胞内物质和维持细胞稳态的细胞器。研究表明,溶酶体不仅具有降解功能,还具有胞吐、质膜修复重塑、自噬、调节脂质代谢、参与免疫反应等作用。溶酶体存在于所有真核细胞中,包括肾小球细胞。最近的研究显示,肾小球细胞内有丰富的溶酶体,溶酶体功能紊乱参与多种肾小球疾病的发生。本文通过对溶酶体功能的解析、溶酶体与肾小球固有细胞的关系及肾小球疾病中溶酶体功能障碍三个方面进行综述,为肾小球疾病的机制研究提供新的思路。
端爱萍高少辉(综述)鲍浩(审校)
关键词:溶酶体生物学功能肾小球疾病
溶酶体相关细胞器:生物发生与功能
2024年
溶酶体相关细胞器是真核动物细胞中功能特异的细胞器,其装配、成熟及运输过程需要借助内体–溶酶体运输途经。该文总结了具有代表性的四种溶酶体相关细胞器(黑素小体、血小板致密颗粒、大致密核心颗粒及Weibel-Palade小体)的结构、功能、生物发生的分子细胞机制,为更深入了解溶酶体相关细胞器的生理和病理意义提供参考。
王翘楚郝振华马静陈元颖李巍
关键词:白化病囊泡运输
针刺调控溶酶体酸化改善阿尔茨海默病的作用机制探析
2024年
阿尔茨海默病是一种老年神经退行性疾病,随着中国老年人人数增加,其患者数量逐年增加。自噬溶酶体功能障碍是导致阿尔茨海默病发生的关键因素。针刺作为一种非药物治疗手段,可以改善自噬异常,激活溶酶体功能,从而提高对异常聚集蛋白和受损伤细胞器的清除,改善阿尔茨海默患者的认知功能障碍。本研究阐述了溶酶体酸化障碍在阿尔茨海默病发生发展中的作用机制,以期针刺通过激活调控溶酶体酸化功能以此改善阿尔茨海默病作用机制,旨在为阿尔茨海默病的预防和治疗提供新策略,为临床推广运用针刺治疗阿尔茨海默病提供依据。
杨佳一王鑫汪子栋陶宜琳吴国庆徐骁腾李志刚
关键词:阿尔茨海默病针刺
CD38经TFEB介导促进溶酶体再生而调节巨噬细胞胆固醇外流
2024年
目的:探讨CD38对巨噬细胞溶酶体再生及胆固醇外流的影响。方法:以低密度脂蛋白(LDL)受体敲除(LDLr^(-/-))小鼠的骨髓源性巨噬细胞为细胞模型。采用活细胞成像系统观察烟酸腺嘌呤二核苷酸磷酸(NAADP)对巨噬细胞溶酶体数量的影响;利用ELISA检测巨噬细胞内NAADP的水平;细胞经NA处理后,利用RT-q PCR检测CD38 m RNA表达,利用Western blot检测CD38蛋白表达和转录因子EB(TFEB)磷酸化水平;利用激光共聚焦技术观察CD38/NAADP信号通路对溶酶体数量和胆固醇外流的影响。结果:NAADP可显著增加巨噬细胞中溶酶体的数量(P<0.05),这种效应可被NAADP拮抗剂NED-19、Ca^(2+)螯合剂BAPTA及钙调磷酸酶抑制剂Cs A明显抑制(P<0.05);CD38可明显促进巨噬细胞中NAADP的合成(P<0.05);NAADP合成底物NA可明显促进CD38 m RNA和蛋白表达(P<0.05);NA还可显著降低TFEB的磷酸化水平,且这一效应也可被NED-19、BAPTA和Cs A明显抑制(P<0.05);阻断CD38/NAADP信号通路可明显抑制NA诱导的溶酶体数量增加和溶酶体游离胆固醇及胞质胆固醇酯的外流(P<0.05);在LDLr/CD38双基因敲除巨噬细胞中,NA诱导的溶酶体数量增加和溶酶体游离胆固醇及胞质胆固醇酯的外流效应消失,CD38基因回补后,这一效应即可恢复(P<0.05)。结论:CD38可经TFEB介导,触发巨噬细胞溶酶体再生,进而促进巨噬细胞溶酶体游离胆固醇和胞质中胆固醇酯的外流。
许浩孙雪妮吴天祺刘进源黄倩琳莫蝶王嘉馨陈沈娴邓伯丹许小洋
关键词:CD38巨噬细胞胆固醇
The autophagy-lysosome pathway:a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease
2025年
Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.
Fengjuan JiaoLingyan MengKang DuXuezhi Li
关键词:AUTOPHAGYΑ-SYNUCLEIN
Role of lysosomal trafficking regulator in autophagic lysosome reformation in neurons:a disease perspective
2024年
Lysosomes are discrete organelles that act as recycling centers for extracellular and intracellular materials,playing a pivotal role in maintaining cellular homeostasis.Their acidic environment,maintained by numerous hydrolytic enzymes,facilitates substrate degradation.Dysfunction in lysosomal processes can lead to abnormal substrate degradation,significantly impacting cellular homeostasis.High energy-demanding cells,such as post-mitotic neurons,are especially vulnerable to these changes,often resulting in neurological diseases.Autophagy,a conserved catabolic process,requires extensive lysosomal utilization.It plays a key role in removing unnecessary intracellular components,ensuring cellular homeostasis,and promoting cell survival during stress conditions such as starvation,infection,or cellular damage.
Prashant SharmaJenny Serra-VinardellWendy J.IntroneMay Christine V.Malicdan
关键词:HOMEOSTASISLYSOSOMAL
原花青素通过转录因子EB诱导的自噬-溶酶体途径促进人牙周膜干细胞成骨分化的研究
2024年
目的研究原花青素(PA)调节人牙周膜干细胞(PDLSCs)成骨分化的具体机制,探讨PA对转录因子EB(TFEB)的表达和自噬-溶酶体途径的影响。方法将PDLSCs分为对照组和PA组,通过转录组测序(RNA Seq)分析差异表达基因,通过实时荧光定量PCR(RT-qPCR)、碱性磷酸酶(ALP)染色和透射电子显微镜(TEM)观察细胞成骨能力和自噬水平。通过划痕实验和Trasnwell实验检测PDLSCs的迁移能力,溶酶体荧光探针(Lysotracker)染色和免疫荧光染色检测溶酶体的生物发生,蛋白质印迹法检测TFEB总蛋白及其在细胞质和细胞核中的表达,激光扫描共聚焦显微镜(CLSM)观察TFEB的核易位。使用小干扰RNA(siRNA)技术敲低TFEB基因,进行PA处理或无处理。蛋白质印迹法检测细胞中自噬标志物苄氯素1(Beclin1)、微管相关蛋白1轻链3B(LC3B)和成骨标志物Runt相关转录因子2(RUNX2)、ALP和骨钙素的表达。结果与对照组相比,PA组中PDLSCs的成骨和自噬相关基因出现差异性表达(P<0.05)。PA组中成骨相关基因RUNX2(2.32±0.15)、Ⅰ型胶原蛋白ɑ1链(CoL1α1)(1.80±0.18)和自噬相关基因LC3B(1.87±0.08)、Beclin1(1.63±0.08)的mRNA表达水平均显著高于对照组(分别为1.01±0.16、1.00±0.10、1.00±0.07、1.00±0.06)(均P<0.001)。与对照组相比,PA组的ALP活性更高,TEM镜下自噬体和自噬溶酶体数目更多。PA显著促进了PDLSCs的迁移(P<0.05),并增加了溶酶体的数量和溶酶体相关膜蛋白1(LAMP1)的表达。PA组中TFEB总蛋白的相对表达水平(1.49±0.07)和TFEB在细胞核/细胞质中的相对表达水平(1.52±0.12)均显著高于对照组(分别为1.00±0.11、1.00±0.13)(均P<0.01)。PA组TFEB的细胞核/细胞质相对荧光强度(0.79±0.90)也显著高于对照组(0.11±0.08)(t=3.49,P<0.01)。敲低TFEB后,PDLSCs中TFEB(0.64±0.04)、LAMP1(0.69±0.09)、Beclin1(0.60±0.05)和LC3BⅡ/Ⅰ(0.73±0.07)蛋白的表达均显著低于阴性对照组(分别为1.00±0.15、1.00±0.10、1.00±0.05、1.00±0
刘卓李麒麟巫雅欣汪向垚毛靖龚士强
关键词:原花青素类人牙周膜干细胞成骨分化
基于生物信息学构建一个Lysosome-related lncRNA模型来预测肝癌的预后
背景:肝细胞癌(Hepatocellular Carcinoma,HCC)是全球肿瘤相关死亡的主要原因之一,其复杂的生物学特性和异质性构成了临床治疗的重大挑战。溶酶体(lysosome)作为细胞内包裹水解酶的膜结构囊泡,...
白燕萍
关键词:肝癌溶酶体
Cucurbit[7]uril confined phenothiazine bridged bis(bromophenyl pyridine)activated NIR luminescence for lysosome imaging
2024年
Macrocycle confinement induced guest near-infrared(NIR)luminescence was research hotspot currently.Here in,we reported a cucurbit[7]uril(CB[7])confined 3,7-bis((E)-2-(pyridin-4-yl)vinyl)-10-Hphenothiazine bridged bis(4-(4-bromophenyl)pyridine)(G),which not only boosted its NIR luminescence but also realized detection of HClO/ClO^(-)in living cells and lysosome imaging.Fluorescence spectroscopy experiments were performed to calculate the detection ability of probe G to HClO/ClO^(-)up to 147 nmol/L.As compared with G,supramolecular probe G■CB[7]formed after encapsulated by CB[7],the detection ability towards HClO/ClO^(-)was improved to 24 nmol/L which was ascribe to the macrocycle CB[7]confinement increasing the fluorescence intensity to 103 folds.Accompanying the excitation wavelength changing,the fluorescence red-shifted to 820 nm when excited by 570 nm light,which was used to NIR lysosome imaging.Meanwhile,the supramolecular assembly G■CB[7]was also successfully used to highly sense to exogenous HClO/ClO^(-)in RAW 264.7 cells and live animal.
Hui-Juan WangWen-Wen XingZhen-Hai YuYong-Xue LiHeng-Yi ZhangQilin YuHongjie ZhuYao-Yao WangYu Liu
关键词:PHENOTHIAZINE

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