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Ferroptosis-induced anticancer effect of resveratrol with a biomimetic nano-delivery system in colorectal cancer treatment

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Asian Journal of Pharmaceutical Sciences 2022年第5期17卷 751-766页

作者： ziting zhang You Ji Nan Hu Qinqi Yu Xinrui zhang Jie Li Fenglei Wu Huae Xu Qiyun Tang Xiaolin Li Department of Geriatric Gastroenterology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210009China Department of Pharmaceutics School of PharmacyNanjing Medical UniversityNanjing 211166China Department of Oncology the Affiliated Hospital of Kangda College of Nanjing Medical University&the First People’s Hospital of LianyungangLianyungang 222000China

Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation,which may be a potential strategy for cancer therapy.Here we demonstrated for the first time that Resveratrol(RSV),a traditional Chinese medicine(TCM)chemical monomer,could effectually inhibit the growth of colon cancer cells through the ROS-dependent ferroptosis pathway.Mechanistically,RSV evoked the increase of reactive oxygen species and lipid peroxidation in colorectal cancer cells,and eventually lead to ferroptosis.Furthermore,RSV could promote ferroptosis by downregulating the expression of the channel protein solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).To improve the delivery efficiency of RSV,a biomimetic nanocarrier was developed by coating RSV-loaded poly(ε-caprolactone)-poly(ethylene glycol)(PCL-PEG)nanoparticles with erythrocyte membrane(RSV-NPs@RBCm).The RSV-NPs@RBCm provide the possibility to escape macrophage phagocytosis and have a long circulation effect.In addition,when coupled with a tumor-penetrating peptide iRGD,which could trigger enhanced tissue penetration tumor-specifically,the delivery of RSV-NPs@RBCm into tumors would be significantly improved results from the in vivo study demonstrated an excellent treatment efficacy for CRC.Altogether,our study highlighted the therapeutic potential of RSV as a ferroptosis-inducing anticancer agent and when loaded into a biomimetic nanoplatform,it might pave the way for the application of RSV loaded nanosystems for colorectal cancer treatment.

关键词： Resveratrol Red-blood-cell membrane Colorectal cancer Ferroptosis IRGD

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产出导向法在高职英语教学中的应用初探

科教导刊 2024年第1期 133-135页

作者：张子婷上海东海职业技术学院上海200241

产出导向法是针对我国高校外语教学所面临问题而提出的,拥有鲜明中国特色的外语教学理论,其实践应用能够有效推进外语课堂教学目标的实现,并对学生英语应用能力的培养发挥着积极的作用。本文阐述了产出导向法的概念,对比了产出导向法与... 详细信息

产出导向法是针对我国高校外语教学所面临问题而提出的,拥有鲜明中国特色的外语教学理论,其实践应用能够有效推进外语课堂教学目标的实现,并对学生英语应用能力的培养发挥着积极的作用。本文阐述了产出导向法的概念,对比了产出导向法与任务型教学法的区别及其实施的意义,分析了当前高职英语教学的现状与问题,并基于产出导向法提出切实有效的解决方案。

关键词：产出导向法高职英语教学理念教学实践

Forecasting the volatility of EUA futures with economic policy uncertainty using the GARCH‑MIDAS model

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Financial Innovation 2021年第1期7卷 1615-1633页

作者： Jian Liu ziting zhang Lizhao Yan Fenghua Wen School of Economics and Management Changsha University of Science and TechnologyChangshaHunanPeople’s Republic of China School of Business Hunan Normal UniversityChangshaHunanPeople’s Republic of China Business School Central South UniverdityChangshaHunanPeople’s Republic of China

This study investigates the impact of economic policy uncertainty(EPU)on the volatility of European Union(EU)carbon futures prices and whether it has predictive power for the volatility of carbon futures prices.The GARCH-MIDAS model is applied for evaluating the impact of different EPU indexes on the price volatility of European Union Allowance(EUA)futures.We then compare the predictive power for the volatility of the two GARCH-MIDAS models based on different EPU indexes and six GARCH-type models.Our empirical results show that the GARCH-MIDAS models,which exhibit superior out-of-sample predictive ability,outperform GARCH-type models.The results also indicate that EPU has noticeable effect on the volatility of EUA futures.Specifically,the forecast accuracy of the EU EPU index is significantly higher than that of the global EPU index.Robustness checks further confirm that the EPU index(especially the EPU index of the EU)has strong predictive power for EUA futures prices.Additionally,using the volatility forecasting methods that GARCH-MIDAS models combine with the EPU index,investors can construct their portfolios to realize economic returns.

关键词： EUA Economic policy uncertainty GARCH-MIDAS Volatility forecasting Futures

BTB与CNC同源蛋白1通过调节MYC相关因子X二聚化蛋白1基因对套细胞淋巴瘤发生发展的影响

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癌症进展 2024年第6期22卷 610-618页

作者：张紫婷张寒北京协和医学院/中国医学科学院/医学生物学研究所昆明6501180

目的探讨BTB与CNC同源蛋白1(BACH1)通过调节MYC相关因子X二聚化蛋白1(MXD1)基因对套细胞淋巴瘤(MCL)发生发展的影响。方法采用靶向剪切及转座酶技术(CUT&Tag)检测BACH1下游靶基因,并通过序列比对分析寻找BACH1与MXD1的结合位点。通过... 详细信息

目的探讨BTB与CNC同源蛋白1(BACH1)通过调节MYC相关因子X二聚化蛋白1(MXD1)基因对套细胞淋巴瘤(MCL)发生发展的影响。方法采用靶向剪切及转座酶技术(CUT&Tag)检测BACH1下游靶基因,并通过序列比对分析寻找BACH1与MXD1的结合位点。通过双荧光素酶报告基因系统验证BACH1对MXD1的调控作用,并采用慢病毒技术构建BACH1过表达及敲低的稳转MCL细胞株,采用蛋白质印迹法(Western blot)检测MXD1蛋白表达水平。应用GSE16411数据集分析MCL细胞和正常B细胞中MXD1 m RNA相对表达量。应用GSE132929及GSE21452数据集筛选MXD1共表达基因,对MXD1共表达基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)信号通路富集分析。采用噻唑蓝(MTT)法检测MXD1正相关基因应激诱导磷蛋白1同源物含U-框蛋白1(STUB1)的特异性激活剂YL109处理后MCL细胞的活力。结果 BACH1能够靶向结合MXD1并抑制MXD1基因的启动子活性。BACH1敲低后MXD1蛋白表达水平升高,而BACH1过表达后MXD1蛋白表达水平降低。通过GSE16411数据集分析发现,MCL细胞中MXD1 mRNA相对表达量明显低于正常B细胞,差异有统计学意义(P﹤0.01)。在GSE132929数据集中筛选出2222个MXD1共表达基因,在GSE21452数据集中筛选出503个MXD1共表达基因。GO分析显示,MXD1共表达基因主要富集于信号转导、蛋白质磷酸化、细胞葡萄糖醛酸化、类黄酮葡萄糖醛酸化等代谢相关的生物学过程;KEGG信号通路分析显示,MXD1共表达基因主要富集于肝脏发育的代谢途径、蛋白质的消化和吸收、Janus激酶(JAK)/信号转导及转录激活因子(STAT)信号通路等。采用YL109处理MCL细胞后可显著降低细胞存活率。结论 BACH1通过结合MXD1近端启动子负向调控MXD1的表达水平,且BACH1介导的MXD1表达改变很可能通过调控代谢过程参与MCL的发生发展。

关键词：套细胞淋巴瘤 BTB与CNC同源蛋白1 MYC相关因子X二聚化蛋白1

中华优秀传统文化赋能乡村振兴的现实困境与实践路径

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智慧农业导刊 2024年第11期4卷 37-42页

作者：黄生成张紫婷江西理工大学马克思主义学院江西赣州341000

党的二十大报告提出,全面推进乡村振兴。中华优秀传统文化赋能乡村振兴不仅为乡村振兴战略提供丰厚的精神文化养料,还为传承中华优秀传统文化提供有效途径。就其重大意义而言,可以提升村民文化素养、增强村民价值认同、挖掘乡村文化产... 详细信息

党的二十大报告提出,全面推进乡村振兴。中华优秀传统文化赋能乡村振兴不仅为乡村振兴战略提供丰厚的精神文化养料,还为传承中华优秀传统文化提供有效途径。就其重大意义而言,可以提升村民文化素养、增强村民价值认同、挖掘乡村文化产业。就其现实困境而言,村民保护传承意识淡薄、乡村人才队伍不健全、文化资源创新动力不足。就其实践路径而言,以讲好文化故事,催生中华优秀传统文化赋能乡村振兴的文化自信;以完善队伍建设,为中华优秀传统文化赋能乡村振兴培育文化人才;以盘活文化资源,融入生产生活为中华优秀传统文化赋能乡村振兴提供动力支持。

关键词：乡村振兴中华优秀传统文化现实困境实践路径文化振兴

Superior in vitro anticancer effect of biomimetic paclitaxel and triptolide co-delivery system in gastric cancer

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The Journal of Biomedical Research 2021年第4期35卷 327-338页

作者： Siwan Wang Hui Jiang Jia Wang Haisi Wu Ting Wu Mengnan Ni Qianqian Zhao You Ji ziting zhang Chunming Tang Huae Xu Department of Pharmaceutics School of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China Jiangsu Key Laboratory of Molecular and Translational Cancer Research Affiliated Cancer Hospital of Nanjing Medical UniversityJiangsu Cancer HospitalJiangsu Institute of Cancer ResearchNanjingJiangsu 210009China Department of Geriatric Gastroenterology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China

As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of PTX.Considering the poor solubility of both drugs,we developed a red blood cell membrane-biomimetic nanosystem,an emerging tool in drug delivery,to co-load paclitaxel and triptolide(red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid)[PLGA]nanoparticles,RP(P/T)).The successful preparation was confirmed in terms of particle size,morphology,and surface markers assays.This biomimetic system could prolong circulation and escape immune surveillance.And these properties were verified by stability,in vitro drug release,and cellular uptake assays.Moreover,the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T)to free drugs.The enhanced antitumor effects of RP(P/T)on migration and invasion were also evaluated by wound-healing and transwell assays.Overall,the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.

关键词： paclitaxel triptolide red-blood-cell membrane gastric cancer

纤维蛋白原Bβ15-42肽在细胞水平对缺血再灌注急性肾损伤线粒体自噬的影响

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医学研究杂志 2024年第6期53卷 65-69页

作者：张紫婷贾珺丹仇文芳乔玉峰山西医科大学第五临床医学院、山西省人民医院太原030012

目的探讨纤维蛋白原Bβ15-42肽(fibrin-derived peptide Bβ15-42,FgBβ15-42)在细胞水平对缺血再灌注急性肾损伤(acute kidney injury,AKI)线粒体自噬的影响。方法体外培养人肾小管上皮细胞,随机分为5组,即正常对照组(Control组)、缺... 详细信息

目的探讨纤维蛋白原Bβ15-42肽(fibrin-derived peptide Bβ15-42,FgBβ15-42)在细胞水平对缺血再灌注急性肾损伤(acute kidney injury,AKI)线粒体自噬的影响。方法体外培养人肾小管上皮细胞,随机分为5组,即正常对照组(Control组)、缺氧复氧(hypoxia/reoxygenation,H/R)模型组(H/R组)、H/R模型+9μmol/L FgBβ15-42肽组(Fg组)、H/R模型+20μmol/L氯喹组(CQ组)、H/R模型+9μmol/L FgBβ15-42肽+20μmol/L氯喹组(Fg+CQ组)。Control组:将同质化细胞置于完全培养基中,在有氧(5%CO_(2),21%O_(2))条件下培养28h。H/R组:细胞用无糖、无血清DMEM/F12培养基在缺氧(5%CO_(2),1%O_(2)和94%N 2)条件下培养24h,再更换含血清的DMEM/F12培养基置于有氧(5%CO_(2),21%O_(2))环境中4h。Fg组:在复氧时加入FgBβ15-42肽9μmol/L进行干预。CQ组:在进行同质化处理时加入氯喹进行预处理(20μmol/L),后序步骤同H/R组。Fg+CQ组:按照上述CQ组及FgBβ15-42组在不同时间段的加药顺序、剂量,及H/R组的造模时间进行干预。干预结束后采用CCK-8法检测HK2细胞活力;电子显微镜观察线粒体形态、线粒体自噬体结构及数量;Western blot法检测自噬相关蛋白p62、LC3的表达水平。结果与Control组比较,H/R组细胞的存活率下降(P<0.01);线粒体损伤明显,出现了肿胀、棘断裂等,且线粒体自噬体的数目增多;自噬标志性蛋白LC-3Ⅱ/Ⅰ表达上调(P<0.05),自噬底物蛋白p62表达下调(P<0.01)。与H/R组比较,Fg组、CQ组、Fg+CQ组细胞的存活率回升(P<0.01),线粒体自噬体减少,LC-3Ⅱ/Ⅰ表达下调(P<0.01),p62表达上调(P<0.05),细胞自噬被抑制。结论FgBβ15-42肽干预后可降低H/R-AKI细胞中自噬及线粒体自噬水平,对HK2细胞H/R损伤有保护作用。

关键词：线粒体自噬缺血再灌注损伤缺氧复氧损伤 FgBβ15-42肽急性肾损伤

Enlarged DNA unwinding by Nme2Cas9 permits a broadened base editing window beyond the protospacer

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Science China(Life Sciences) 2024年第2期67卷 424-427页

作者： ziting Chen Xiangyang Li Qian zhang Wenjun Sun Xiaoxuan Song Xia zhang Xingxu Huang Bo Sun School of Life Science and Technology and Gene Editing Center ShanghaiTech UniversityShanghai 201210China Zhejiang Lab HangzhouZhejiang 311121China CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China

Dear Editor,Base editing has been developed to be one of the effective CRISPR-based gene editing techniques(Rees and Liu,2018).Base editors(BEs)take advantage of DNAmodifying enzymes fused with a catalytically impaired CRISPR protein to install base mutations.In BE,DNA-modifying enzymes often process nontarget singlestranded DNA(NTS)generated by Cas proteins.

关键词： install base winding

Neutrophil extracellular traps induced by interleukin 8 via CXCR1/2 promote the progression of gastric carcinoma through transcription factor IIB-related factor 1 and cyclin

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Genes & Diseases 2024年第2期11卷 575-578页

作者： Qianling Wang Yiyin zhang Wenxi Ding Cheng Feng Yuyan Wang Xiaoli Wei ziting Qu Hui Wang Xiaoying Liu Hua Wang Kangsheng Gu Department of Oncology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China School of Life Sciences Anhui Medical UniversityHefeiAnhui 230032China

Neutrophils constitute a significant portion of the immune cells present within the tumor microenvironment.Evidence generated by our group has confirmed neutrophils to be an adverse independent prognostic factor affecting the disease-free survival of gastric carcinoma(GC)patients.1 Neutrophil extracellular traps(NETs),protein-covered DNA webs that interact with tumor cells in the tumor microenvironment,were detected in GC tissues and found to clinically associated with disease progression in our previous study.2 NETosis could be mediated by a series of agonists,such as interleukin 8(IL-8).3 However,the mechanism of IL-8 in the progression of GC occurs via NETs remains unclear.In this study,we identified that IL-8-mediated NETosis can promote the proliferation,migration,and invasion of GC cells in vitro,which can be abrogated by NET degradation through deoxyribonucleaseI(DNase I)or IL-8 suppression through neutralizing antibodies.Disruption of NETs by DNase I or blockade of the IL-8-CXC chemokine receptor 2(CXCR2)axis could result in growth retardation in mouse models.We also confirmed that NETs may influence the biological behavior of GC cells by up-regulating the expression of transcription factor IB-related factor 1(BRF1)and cyclin p21/p27.

关键词： invasion gastric progression