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Miriplatin-loaded liposome,as a novel mitophagy inducer,suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication

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Acta Pharmaceutica Sinica B 2023年第11期13卷 4477-4501页

作者： Xiaowei Wang Mengyan Wang Meilian Cai Rongguang Shao Guimin Xia wuli zhao State Key Laboratory of Respiratory Health and Multimorbidity Key Laboratory of Antibiotic BioengineeringMinistry of HealthLaboratory of OncologyInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Pharmaceutics Department Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Pancreatic cancer is a more aggressive and refractory *** and toxicity limit drug ***,we report a lower toxic and higher effective miriplatin(MPt)-loaded liposome,LMPt,exhibiting totally different anti-cancer mechanism from previously reported platinum *** in gemcitabine(GEM)-resistant/sensitive(GEM-R/S)pancreatic cancer cells,LMPt exhibits prominent anti-cancer activity,led by faster cellular entry-induced larger accumulation of *** level of caveolin-1(Cav-1)determines entry rate and switch of entry pathways of LMPt,indicating a novel role of Cav-1 in nanoparticle *** endosome-lysosome processing,in unchanged metabolite,MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM,to degrade POLG and ***,via PINK1-Parkin axis,mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA(mtDNA)replication ***,POLG and TFAM are identified as novel prognostic markers of pancreatic cancer,and mtDNA replication-induced mitophagy blocking mediates their pro-cancer *** findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA(target of most platinum agents),and totally distinct mechanism of MPt and other formulations of ***-assembly offers LMPt special efficacy and *** action and characteristic mechanism make LMPt a promising cancer candidate.

关键词： Miriplatin-loaded liposome Pancreatic cancer Caveolae-mediated endocytosis Caveolin-1 Mitophagy Mitochondria DNA POLG TFAM

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Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents

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Acta Pharmaceutica Sinica B 2016年第3期6卷 222-228页

作者： Chongwen Bi Cheng Ye Yinghong Li wuli zhao Rongguang Shao Danqing Song Institute of Medicinal Biotechnology Chinese Academy of Medical Science & Peking Union Medical College Tianjin Medical University General Hospital

Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 30-substituents at the 11–side chain were synthesized and evaluated for their anticancer activity from sophoridine(1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a–b, alkenes 7a–b and sophoridinic amines 14a–b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin(AMD)-susceptible and resistant MCF-7 breast carcinoma cells,indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.

关键词： Sophoridinic derivatives Synthesis Structure–activity relationship Anticancer Drug resistance

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Myofibrillogenesis regulator-1 promotes cell adhesion and migration in human hepatoma cells

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Chinese Science Bulletin 2013年第24期58卷 3007-3014页

作者： zhao wuli HE HongWei REN KaiHuan ZHANG Hao CHEN Yi SHAO RongGuang Ministry of Health Key Laboratory of Antibiotic Bioengineering Department of Oncology Institute of Medicinal Biotechnology Peking Union Medical College Chinese Academy of Medical Sciences

Myofibrillogenesis regulator-1 (MR-1) is a gene overexpressed usually in many human cancers. However, the effects of MR-1 on cell proliferation, adhesion, migration and genome-wide gene regulation are still unclear. In this study, a human hepatoma cell line that highly overexpresses MR-1, BEL-7402/MR-1 cells was established. While the high expression of MR-1 did not promote cell proliferation, it significantly increased cell spreading, adhesion and migration compared with control cells. A total of 147 genes were regulated by MR-1 expression, 46 genes were down-regulated and 101 genes were up-regulated by MR-1 overexpression. Many of these genes were related to cell adhesion, cytoskeletal regulation, MAPK signaling, and cell cycle related pathways. Western blot analysis further confirmed the regulation of pathways associated with migration by MR-1. These results suggest that MR-1 is involved in the regulation of cancer cell adhesion, migration and related gene expression.

关键词：人肝癌细胞株迁移黏附人类基因表达调控调节器细胞粘附 blot分析

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The novel ER stress inducer Sec C triggers apoptosis by sulfating ER cysteine residues and degrading YAP via ER stress in pancreatic cancer cells

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Acta Pharmaceutica Sinica B 2022年第1期12卷 210-227页

作者： Junxia Wang Minghua Chen Mengyan Wang Wenxia zhao Conghui Zhang Xiujun Liu Meilian Cai Yuhan Qiu Tianshu Zhang Huimin Zhou wuli zhao Shuyi Si Rongguang Shao Key Laboratory of Antibiotic Bioengineering Ministry of HealthLaboratory of OncologyInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Pancreatic adenocarcinoma(PAAD) is one of the most lethal malignancies. Although gemcitabine(GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C(Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect(80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-L-cysteine(NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum(ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation(ERAD) ubiquitinates anddownregulates YAP to enhance ER stress via destruction complex(YAP-Axin-GSK-βTr CP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

关键词： Pancreatic cancer Secoemestrin C YAP degradation ER stress inducer Resistance Fast shrinkage YAP destruction complex Lipid droplet formation

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Salmonella typhimurium strain SL7207 induces apoptosis and inhibits the growth of HepG2 hepatoma cells in vitro and in vivo

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Acta Pharmaceutica Sinica B 2012年第6期2卷 562-568页

作者： Baowei Li Hongwei He Shenghua Zhang wuli zhao Naren Li Rongguang Shao MOH Key Laboratory of Antibiotic Bioengineering Department of OncologyInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Salmonella typhimurium is probably most extensively studied tumor-targeting bacteria and SL7207 is one of its attenuated ***7207 was first made for bacterial vaccine development and its therapeutic efficacy and safety for hepatoellular carcinoma has not been *** this study,the inhibitory ability of SL 7207-lux on human hepatoma HepG2 cells was tested in vitro and in vivo.A bacterial luminescent gene cluster(lux CDA BE)was transfected into SL7207 to better monitor the invasion of the *** results show that SL7207-lux can rapidly enter HepG2 cells and localize in the *** invasion represses ell proliferation and induces *** vivo real-time invasion studies showed that the bacteria gradually accumulate in the *** enrichment was confirmed by anatomic observation at 5 days after *** 40%of tumor growth was inhibited by SL7207-lxx at 34 days post-treatment without significant loss of body *** area of necrosis of tumor tissue was clearly increased in the treated *** quantification showed that the number of colony-forming units per gram of bacteria within tumor tissue was approximately 1000-fold higher than that of liver and *** data suggest that attenuated *** strain SL7207 has potential for the treatment of cancers.

关键词： Salmonella typhimurium Hepatocellular carci-noma Apoptosis Cancer therapy

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电感耦合等离子体发射光谱测定钼铝合金中硅含量的方法研究

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分析科学学报 2021年第5期37卷 711-715页

作者：罗策李剑颜燕刘婷康琼赵武丽卢凡宝钛集团有限公司陕西宝鸡721014 陕西省宝鸡教育学院陕西宝鸡721000

采用王水、氢氟酸在180℃加热条件下溶解试样,全面分析了硅元素的212.412、221.667、251.611、252.851、288.158 nm五条分析谱线的受干扰情况,最终选择了灵敏度和信噪比较高、受钼基体干扰程度较小的Si 288.158 nm为分析谱线。使用多谱... 详细信息

采用王水、氢氟酸在180℃加热条件下溶解试样,全面分析了硅元素的212.412、221.667、251.611、252.851、288.158 nm五条分析谱线的受干扰情况,最终选择了灵敏度和信噪比较高、受钼基体干扰程度较小的Si 288.158 nm为分析谱线。使用多谱线拟合(MSF)技术建立了Si 288.158 nm的光谱校正模型,通过校正模型对样品检测信号峰进行了校正,消除了基体钼(Mo 288.137 nm)的光谱干扰,建立了电感耦合等离子体发射光谱法(ICP-OES)测定钼铝合金中硅含量的方法。该方法在0.10~5.00 mg/L范围内(对应固体样品中硅的质量分数范围为0.010%~0.50%),硅的工作曲线线性关系良好,相关系数为0.9995;方法检出限和定量限分别为23μg/g和76μg/g;对3个不同含量的钼铝样品中的硅含量进行了测定,测定结果的相对标准偏差(RSD)在0.76%~1.36%之间,加标回收率在98.0%~106%范围,与标准(YS/T 1075.3-2015)中钼蓝分光光度法的测定结果一致。

关键词：电感耦合等离子体发射光谱法光谱干扰多谱线拟合钼铝合金硅

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In situ polymerization of poly(3,4-ethylenedioxythiophene)protective layer towards stable zinc anode

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Nano Research 2025年第1期18卷 382-394页

作者： Debin Luo Peng Zhou Xiaowei Lv Panpan Sun Xiaohua Sun Hewei zhao College of Materials and Chemical Engineering Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion MaterialsChina Three Gorges UniversityYichang 443002China Hubei Three Gorges Laboratory Yichang 443007China School of Chemistry Beihang UniversityBeijing 100191China

Aqueous zinc-ion devices are considered promising candidates for energy storage due to their high safety,low cost and relatively high energy ***,the dendrite growth,hydrogen evolution reaction(HER)and corrosion of the zinc anode significantly limit the development of Zn-ion ***,an inexpensive poly(3,4-ethylenedioxythiophene)(PEDOT)protective layer was constructed in situ on the Zn surface using electropolymerization to suppress dendrite growth and side reactions,thereby enhancing the reversibility of *** and theoretical calculations revealed that this hydrophilic protective layer promotes the desolvation process of hydrated Zn^(2+)and facilitates the transport of zinc ions,thus improving the thermodynamic and kinetic properties of Zn^(2+)deposition and inhibiting interfacial side ***,the optimized PEDOT@Zn symmetric battery exhibited a cycling stability exceeding 1250 h at 0.5 mA·cm^(-2)and 0.25 mAh·cm^(-2),with a significantly reduced overpotential(from 91.8 to 35 mV).With the assistance of the PEDOT protective layer,the PEDOT@Zn//Cu battery maintained approximately 99.5%Coulombic efficiency after 450 ***-situ scanning electron microscopy(SEM)and in situ optical microscopy characterizations further confirmed that the PEDOT protective layer can effectively suppress the growth of zinc ***,the Zn-ion capacitors assembled by the PEDOT@Zn and activated carbon also demonstrated outstanding cycling stability.

关键词： zinc-ion devices zinc anode poly(3 4-ethylenedioxythiophene)(PEDOT) dendrite desolvation process

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TRIPLET combined with microwave ablation:A novel treatment for advanced hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 10-12页

作者： Fei-Yu zhao Guo-Wei Si Nian-Song Qian Department of Thoracic Oncology Respiratory and Critical Care MedicineThe Eighth Medical Center of People’s Liberation Army General HospitalBeijing 100853China Department of Gastroenterology Fourth Medical CentreGeneral Hospital of the People's Liberation ArmyBeijing 100142China Senior Department of Thoracic Oncology Respiratory and Critical Care MedicineThe Eighth Medical Center of People’s Liberation Army General HospitalBeijing 100091China

This editorial comments on a study by Zuo et *** focus is on the efficacy of he-patic arterial infusion chemotherapy combined with camrelizumab and apatinib(the TRIPLET regimen),alongside microwave ablation therapy,in treating advanced hepatocellular carcinoma(HCC).The potential application of this combination therapy for patients with advanced HCC is evaluated.

关键词： Microwave ablation Hepatic arterial infusion chemotherapy Apatinib Camrelizumab Hepatocellular carcinoma

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A new horizon for neuroscience:terahertz biotechnology in brain research

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Neural Regeneration Research 2025年第2期20卷 309-325页

作者： Zhengping Pu Yu Wu Zhongjie Zhu Hongwei zhao Donghong Cui Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry Kangci Hospital of JiaxingTongxiangZhejiang ProvinceChina Shanghai Synchrotron Radiation Facility Shanghai Advanced Research InstituteChinese Academy of SciencesShanghaiChina Key Laboratory of Interfacial Physics and Technology Shanghai Institute of Applied PhysicsChinese Academy of ScienceShanghaiChina National Facility for Protein Science in Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghaiChina

Terahertz biotechnology has been increasingly applied in various biomedical fields and has especially shown great potential for application in brain *** this article,we review the development of terahertz biotechnology and its applications in the field of *** evidence indicates promising prospects for the use of terahertz spectroscopy and terahertz imaging techniques in the diagnosis of amyloid disease,cerebrovascular disease,glioma,psychiatric disease,traumatic brain injury,and myelin *** vitro and animal experiments have also demonstrated the potential therapeutic value of terahertz technology in some neuropsychiatric *** the precise underlying mechanism of the interactions between terahertz electromagnetic waves and the biosystem is not yet fully understood,the research progress in this field shows great potential for biomedical noninvasive diagnostic and therapeutic ***,the biosafety of terahertz radiation requires further exploration regarding its two-sided efficacy in practical *** review demonstrates that terahertz biotechnology has the potential to be a promising method in the field of neuropsychiatry based on its unique advantages.

关键词： biological effect brain neuron neuropsychiatry neuroscience non-thermal effect terahertz imaging terahertz radiation terahertz spectroscopy terahertz technology

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Defect self-assembly of metal-organic framework triggers ferroptosis to overcome resistance

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Bioactive Materials 2023年第1期19卷 1-11页

作者： Haibao Peng Xingcai Zhang Peng Yang Jiaxu zhao Wei Zhang Nianping Feng wuli Yang Jing Tang Institute for Translational Brain Research Fudan UniversityShanghai200032China State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceFudan UniversityShanghai200438China Department of Pharmaceutical Sciences Shanghai University of Traditional Chinese MedicineShanghai201203China Department of Materials Science and Engineering Stanford UniversityStanfordCA94305United States School of Engineering and Applied Sciences Harvard UniversityCambridgeMA02138United States Engineering Research Center of Molecular-and Neuro-imaging of Ministry of Education School of Life Science and TechnologyXidian University710126China

The emergence of multidrug treatment resistance presents a hurdle for the successful chemotherapy of ***,resulting from the iron-dependent accumulation of lipid peroxides,has the potential to reverse multidrug ***,simultaneous delivery of the iron sources,ferroptosis inducers,drugs,and enhanced circulation carriers within matrices remains a significant ***,we designed and fabricated a defect self-assembly of metal-organic framework(MOF)-red blood cell(RBC)membrane-camouflaged multi-drug-delivery nanoplatform for combined ferroptosis-apoptosis treatment of multidrug-resistant *** and chemotherapeutic drugs are embedded in the centre of the iron(III)-based MOF at defect sites by coordination with metal clusters during a one-pot solvothermal synthesis *** RBC membrane could camouflage the nanoplatform for longer *** results demonstrate that this defect self-assembly-enabled MOF-membrane-camouflaged nanoplatform could deplete the glutathione,amplify the reactive oxidative species oxidative stress,and enable remarkable anticancer *** work provides an alternative strategy for overcoming multidrug resistance,which could regulate the fluidity and permeability of the cell membrane by ferroptosis to downregulate of P-glycoprotein protein expression by *** defect self-assembly-enabled MOF-membrane-camouflaged multi-drug-delivery nanoplatform has great therapeutic potential.

关键词： Metal-organic framework Defect nanostructures Ferroptosis Membrane-camouflaged Multi-drug-delivery

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