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Mitophagy and cGAS-STING crosstalk in neuroinflammation

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3327-3361页

作者： Xiaogang Zhou Jing Wang Lu Yu gan qiao Dalian Qin Betty Yuen-Kwan Law Fang Ren Jianming Wu Anguo Wu Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou 646000China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacao SAR 999078China Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine Chongqing Traditional Chinese Medicine HospitalChongqing 400021China

Mitophagy,essential for mitochondrial health,selectively degrades damaged *** is intricately linked to the cGAS-STING pathway,which is crucial for innate *** pathway responds to mitochondrial DNA and is associated with cellular stress *** review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS-STING *** critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions,primarily through the accumulation of damaged mitochondria,which activates the cGAS-STING *** activation prompts the production of pro-inflammatory cytokines,exacerbating *** review emphasizes the interaction between mitophagy and the cGAS-STING *** mitophagy may suppress the cGAS-STING pathway,offering protection against ***,impaired mitophagy may activate the cGAS-STING pathway,leading to chronic ***,we explored how this interaction influences neurodegenerative disorders,suggesting a common mechanism underlying these *** conclusion,there is a need for additional targeted research to unravel the complexities of mitophagy-cGAS-STING interactions and their role in *** review highlights potential therapies targeting these pathways,potentially leading to new treatments for neuroinflammatory and neurodegenerative *** synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.

关键词： Neuroinflammation Mitophagy cGAS-STING Innate immunity Mitochondrial DNA Crosstalk Therapeutic avenues Neurodegenerative diseases

Novel Zn-doped CuO nanocomposites inhibit tumor growth in vitro and in vivo：role of reactive oxygen species-dependent apoptosis and autophagy cross-linked by NF-kappaB pathway

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中国药理学与毒理学杂志 2018年第4期32卷 317-318页

作者： Huan-li XU Ru YUAN Xiao LI Cong LI gan qiao Xiu-kun LIN Department of Pharmacology School of Basic Medical Sciences Capital Medical University Beijing 100069 China

OBJECTIVE Zn-doped CuO nanocomposites(nZn-CuO NPs) are novel nanoparticles synthesized by sonochemical *** study aimed to further investigate the antitumor effects and mechanism of nZn-CuO NPs,as well as the exact mechanism of reactive oxygen species(ROS) on nZn-CuO NPs-induced death using N-acetylcysteine(NAC).METHODS The antitumor effects of nZn-CuO NPs were evaluated by MTS assay and orthotopic transplantation tumor model in nude *** effects of nZn-CuO NPs with or without NAC on ROS production,DNA damage,apoptosis,mitochondrial damage,autophagy,lysosome impairment,and ER and Golgi stress were ***,western blot was used to detect apoptosis and autophagy related proteins,as well as NF-κB pathway related *** nZn-CuO NPs significantly inhibit tumor growth both in vitro and in ***-CuO NPs were able to cause cytotoxicity,ROS production,DAN damage mitochondrial damage,apoptosis,and autophagy,and NAC can attenuate *** studies showed that nZn-CuO NPs induced changes of apoptosis,autophagy and NF-κB pathway related proteins,and NAC can restore *** Overall,our data demonstrated that nZn-CuO NPs could inhibit tumor growth both in vitro and in vivo by ROS-dependent regulation of apoptosis and autophagy,which might be cross-linked by NF-κB pathways.

关键词：超声化学方法抗肿瘤临床分析治疗方法

Water-soluble extract of clove inhibits in vitro and in vivo growth of colon cancer by inducing autophagy

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中国药理学与毒理学杂志 2018年第4期32卷 291-292页

作者： Cong LI Huan-li XU Ye TIAN gan qiao Xiao LI Xiao-hui LIU Xiu-kun LIN Department of Pharmacology Capital Medical University Beijing China.

OBJECTIVE Cloves(Syzygium aromaticumL.) have been used as both a spice and a traditional Chinese medicinal herb for thousands of ***,relatively little is known about its potential anticancer activity and *** this study,we investigated the in vitro and in vivo *** effects and mechanisms of water extract of cloves(WEC) against colorectal *** MTS assay and Colony-formation assay were used to detect the anti-tumor activity of WEC on HT-29 *** in vivo anti-tumor effect of WEC was detected in a subcutaneous transplantation tumor model of human HT-29 *** was detected by flow cytometry and the expressions of autophagy related proteins(Beclin-1 and LC-3 a/b) were determined by western *** MTS result showed that WEC significantly inhibited the viability of HT-29 cells,with the IC50 values of 150 μg·*** colonyformation assay showed that the WEC significantly suppressed colon cancer cells *** also exhibited significant antitumor activity in tumor bearing nude *** cytometry result showed that WEC significantly induced autophagy,and the averaged relative values of fluorescence intensity were206,251,341 and 356 in cells treated with 0,100,150 and 200 μg·mL-1 WEC for 48 *** blot result showed that WEC treatment significantly increased Beclin-1 expression and ratios of LC3-II/*** These result showed that WEC inhibited the growth of colon tumor both in vitro and in vivo,which might be related with autophagy induction,and WEC has potential to be developed as a novel anticancer agent for the treatment of colon cancer.

关键词：丁香中草药肿瘤治疗方法

Granulin A synergizes with cisplatin to inhibit the growth of human hepatocellular carcinoma

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中国药理学与毒理学杂志 2018年第4期32卷 299-300页

作者： gan qiao Huan-li XU Ye TIAN Cong LI Xiao LI Xiao-hui LIU Xiu-kun LIN Department of Pharmacology Capital Medical University Beijing China

OBJECTIVE Granulin A(GRN A),a cytokinesis protein,is derived from proteolysis of *** previous study in our laboratory has shown that GRN A is able to inhibit cancer cell growth *** study aimed to investigate the effect of combination of GRN A and cisplatin on in vitro and in vivo on the growth of hepatocellular *** The in vitro and in vivo antitumor effects of combination of GRN A and Cisplatin were evaluated with MTS assay and *** transplantation tumor ***-Talalay method was used to calculate the combination index(CI).Colony formation assay and flow cytometry were used to detect the effects of GRN A on *** expression of apoptosis-related proteins were detected by Western *** MTS assay showed that GRN A significantly inhibit hepatocellular carcinoma cells growth with the IC50 of 5.6 μmol·L^(-1),and GRN A combined with cisplatin synergistically inhibit hepatocellular carcinoma proliferation,with the CI<*** colony-formation assay showed that GRN A significantly enhanced the inhibitory effects of cisplatin on cellular anchorage-independent *** cytometry showed that GRN A combined with cisplatin synergistically induced apoptosis,with the apoptotic rates of 5.87%,32.74%,35.67% and 67.15% in control,GRN A,Cisplatin,and combination of GRN A and Cisplatin groups,*** blot confirmed that the two drugs synergistically changed the expressions of proteins related to *** vivo experiment indicated that combination of GRN A and cisplatin significantly suppressed tumor growth compared with single drug treatment *** The combination of GRN A and cisplatin resulted in synergistic antitumor effects against hepatocellular carcinoma both in vitro and in vivo.

关键词：细胞因子蛋白蛋白水解治疗方法临床分析

High-throughput screening for amyloid-β binding natural small-molecules based on the combinational use of biolayer interferometry and UHPLC−DAD-Q/TOF-MS/MS

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1723-1739页

作者： Minsong Guo Fengdan Zhu Wenqiao Qiu gan qiao Betty Yuen-Kwan Law Lu Yu Jianming Wu Yong Tang Chonglin Yu Dalian Qin Xiaogang Zhou Anguo Wu Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaSchool of PharmacyEducation Ministry Key Laboratory of Medical ElectrophysiologySouthwest Medical UniversityLuzhou 646000China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyTaipaMacao 999078China Department of Neurosurgery Sichuan Provincial People’s Hospital University of Electronic Science and Technology of ChinaChengdu 610000China

Discovery of drugs rapidly and effectively is an important aspect for Alzheimer's disease(AD).In this study,a novel high-throughput screening(HTS)method aims at screening the small-molecules with amyloid-β(Aβ)binding affinity from natural medicines,based on the combinational use of biolayer interferometry(BLI)and ultra-high-performance liquid chromatography coupled with diode-array detector and quadrupole/time-of-flight tandem mass spectrometry(UHPLC−DAD-Q/TOF-MS/MS)has been firstly ***,the components in natural medicines disassociated from biotinylated Aβwere collected to analyze their potential Aβbinding affinity by UHPLC−DAD-Q/TOF-MS/***,baicalein was confirmed to exhibit the highest binding affinity with Aβin Scutellaria ***,polyporenic acid C(PPAC),dehydrotumulosic acid(DTA),and tumulosic acid(TA)in Kai-Xin-San(KXS)were also identified as potent Aβ*** bioactivity validations indicated that these compounds could inhibit Aβfibrillation,improve the viability in Aβ-induced PC-12 cells,and decrease the Aβcontent and improve the behavioral ability in Caenorhabditis *** molecular docking results confirmed that PPAC,DTA,and TA possessed good binding properties with Aβ.Collectively,the present study has provided a novel and effective HTS method for the identification of natural inhibitors on Aβfibrillation,which may accelerate the process on anti-AD drugs discovery and development.

关键词： Alzheimer’s disease High-throughput screening Biolayer interferometry UHPLCDAD-Q/TOFMS/MS Kai-Xin-San

L2 Syntactic Alignment in the Reading-Writing Integrated Continuation Task: Evidence From Chinese EFL Learners’ Description of Motion Events

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Chinese Journal of Applied Linguistics 2021年第3期44卷 292-313,430页

作者： Min WANG qiao gan Julie BOLAND Xi’an Jiaotong University University of Michigan US

This study investigated how the mode in which the reading-writing integrated continuation task was conducted modulates the effects of second language(L2) syntactic alignment, through the English motion event construction with manner verbs. Ninety Chinese students were assigned to either of the two experimental groups or a control group, and they all experienced a pretest, an alignment phase and a posttest. In the alignment phase, the two experimental groups completed a reading-writing integrated continuation task but in different modes. For the multi-turn mode,participants reconstructed a picture story by continuing the episodes extracted from the story with one episode presented and continued at a time;for the single-turn mode, the first half of the same picture story was presented as a chunk, and then participants read and continued it. Results show that L2 learners aligned with the target structure in completing the story, and the alignment effect was retained in the posttest conducted after a delay of two weeks. Moreover, syntactic alignment was modulated by task mode with the multi-turn group exhibiting stronger immediate and longterm alignment effects. We conclude that the continuation task is a fruitful context for L2 structural alignment, and the magnitude of alignment effect hinges on interactive intensity.

关键词： reading-writing integrated continuation task syntactic alignment task mode interactive intensity motion event construction with manner verbs L2 learning

游客对大型节事活动旅游公共服务感知评价研究——基于第16届广州亚运会期间的考察

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经济地理 2011年第6期31卷 1047-1053,1007页

作者：李爽甘巧林华南师范大学旅游管理系中国广东广州510631

适应旅游发展的新形式,加强和完善节事活动旅游公共服务建设,为游客提供优质、人性化的服务,已成为各级旅游管理部门一项迫切而重要的任务。以第16届广州亚运会期间来广州旅游的国内游客作为研究对象,运用描述性统计分析、因子分析以及... 详细信息

适应旅游发展的新形式,加强和完善节事活动旅游公共服务建设,为游客提供优质、人性化的服务,已成为各级旅游管理部门一项迫切而重要的任务。以第16届广州亚运会期间来广州旅游的国内游客作为研究对象,运用描述性统计分析、因子分析以及IPA等方法从游客感知视角出发,构建节事活动旅游公共服务的评价体系,并找出游客对旅游公共服务评价因子的期望与绩效感知的差异,客观评价广州市第16届亚运会期间的旅游公共服务效果,研究结果可为未来广州市乃至我国其他地区举办大型节事活动供参考。

关键词：旅游公共服务节事活动亚运会广州

乡村旅游社区居民社会排斥的多维度感知——江西婺源李坑村案例的质化研究

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旅游学刊 2011年第8期26卷 87-94页

作者：郭华甘巧林华南师范大学旅游管理系广东广州510631

文章以江西省婺源县李坑村为例,在质化研究的基础上对旅游开发背景下当地居民社会排斥的主观感知状况进行了考察,发现旅游开发给当地社区带来了多方面的变化,这些变化导致社区居民的挫折感、自卑感增加,他们往往从经济排斥、政治排斥、... 详细信息

文章以江西省婺源县李坑村为例,在质化研究的基础上对旅游开发背景下当地居民社会排斥的主观感知状况进行了考察,发现旅游开发给当地社区带来了多方面的变化,这些变化导致社区居民的挫折感、自卑感增加,他们往往从经济排斥、政治排斥、文化排斥和关系排斥等多个维度来感知自身"被排斥"的状况。旅游开发过程中的相关制度设置为社会排斥提供了可能空间,不同利益相关群体在社区中的交互作用成为社会排斥的推动力量,社区居民个体自身能力与认知状况也构成社会排斥的重要原因。从经济、政治、文化及人际关系等多个维度入手消除由旅游开发问题所导致的社会排斥应是乡村旅游可持续发展的重要目标之一。

关键词：乡村旅游社区居民社会排斥感知婺源李坑村

肠道菌群及其代谢产物与T2DM发病机制及干预措施

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中国生物工程杂志 2022年第3期42卷 62-71页

作者：甘巧孟庆雄昆明理工大学生命科学与技术学院昆明650504

2型糖尿病(type 2 diabetes mellitus,T2DM)是一种因胰岛素分泌不足或胰岛素抵抗而引起的慢性代谢疾病,T2DM患病人数的快速增长使治疗和预防T2DM成为世界上亟待解决的医学问题。随着微生物组学技术的进步,肠道菌群及其代谢产物与T2DM的... 详细信息

2型糖尿病(type 2 diabetes mellitus,T2DM)是一种因胰岛素分泌不足或胰岛素抵抗而引起的慢性代谢疾病,T2DM患病人数的快速增长使治疗和预防T2DM成为世界上亟待解决的医学问题。随着微生物组学技术的进步,肠道菌群及其代谢产物与T2DM的研究亦逐渐深入,肠道菌群可能成为治疗和预防T2DM的靶点。肠道菌群及其代谢产物作用于T2DM的潜在机制,主要是参与体内炎症反应、增加肠道短链脂肪酸产量、调节肠道胆汁酸的代谢、调节支链氨基酸的代谢等。目前,治疗T2DM的药物可能会产生一些副作用,而基于肠道菌群干预T2DM的措施相对安全无害。例如,可通过严格控制的特定结构饮食长期摄入或增加益生菌的长期摄取控制血糖,或通过口服可影响肠道菌群生态结构的降糖药物(二甲双胍、阿卡波糖)有效地调控血糖水平。综述基于肠道菌群及其代谢产物诱发T2DM的潜在机制,研讨基于肠道菌群干预T2DM的措施,从肠道菌群的新视角探索治疗T2DM的新方法,为彻底治疗T2DM提供一种新可能。

关键词：肠道菌群 2型糖尿病代谢产物二甲双胍