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Tetrandrine citrate eliminates imatinib-resistant chronic myeloid leukemia cells in vitro and in vivo by inhibiting Bcr-Abl/β-catenin axis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第11期13卷 867-874页

作者： Xiao-hua XU Yi-chao GAN Gen-bo XU Ting CHEN Hong ZHOU Jin-fen TANG ying GU Fei XU ying-ying xie Xiao-ying ZHAO Rong-zhen XU Department of Hematology the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China Department of Cancer Institute the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

Objective:To evaluate the effects of tetrandrine citrate, a novel tetrandrine salt with high water solubility, on the growth of imatinib (IM)-resistant chronic myeloid leukemia (CML) in vitro and in vivo, and reveal action molecular mechanisms. Methods:Cell viability in vitro was measured using methyl thiazolyl tetrazolium (MTT) assay. CML cell growth in vivo was assessed using a xenograft model in nude mice. Bcr-Abl and β-catenin protein levels were determined using Western blotting. Bcr-Abl messenger RNA (mRNA) was measured by reverse transcription polymerase chain reaction (RT-PCR). Flow cytometry (FCM) was used to determine cell cycle status. Results:Tetrandrine citrate inhibited the growth of IM-resistant K562 cells, primary leukemia cells, and primitive CD34 + leukemia cells, and their inhibition concentration that inhibited 50% of target cells (IC 50 ) ranged from 1.20 to 2.97 μg/ml. In contrast, tetrandrine citrate did not affect normal blood cells under the same conditions, and IC 50 values were about 10.12-13.11 μg/ml. Oral administration of tetrandrine citrate caused complete regression of IM-resistant K562 xeno-grafts in nude mice without overt toxicity. Western blot results revealed that treatment of IM-resistant K562 cells with tetrandrine citrate resulted in a significant decrease of both p210 Bcr-Abl and β-catenin proteins, but IM did not affect the Bcr-Abl protein levels. Proteasome inhibitor, MG132, did not prevent tetrandrine-mediated decrease of the p210 Bcr-Abl protein. RT-PCR results showed that tetrandrine treatment caused a decrease of Bcr-Abl mRNA. FCM analysis indicated that tetrandrine induced gap 1 (G 1 ) arrest in CML cells. Conclusions:Tetrandrine citrate is a novel orally active tetrandrine salt with potent anti-tumor activity against IM-resistant K562 cells and CML cells. Tetrandrine citrate-induced growth inhibition of leukemia cells may be involved in the depletion of p210 Bcr-Abl mRNA and β-catenin protein.

关键词： Chronic myeloid leukemia Imatinib-resistance Tetrandrine citrate Bcr-Abl protein β-catenin protein

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Proteomic analysis of glutathione S-transferase isoforms in mouse liver mitochondria

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World Journal of Gastroenterology 2012年第26期18卷 3435-3442页

作者： Hai-Dan Sun Ya-Wei Ru Dong-Juan Zhang Song-Yue Yin Liang Yin ying-ying xie You-Fei Guan Si-Qi Liu Beijing Institute of GenomJcs Chinese Academy of Sciences Beijing 101318 China Department of Physiologyand Pathophysiology Peking University Health Science CenterBeijing 100191 China

AIM:To survey glutathione(GSH) S-transferase(GST) isoforms in mitochondria and to reveal the isoforms' biological significance in diabetic ***:The presence of GSTs in mouse liver mitochondria was systematically screened by two proteomic approaches,namely,GSH affinity chromatography/two dimensional electrophoresis(2DE/MALDI TOF/TOF MS) and SDS-PAGE/LC ESI MS/*** proteomic results were further confirmed by Western blotting using monoclonal antibodies against *** evaluate the liver mitochondrial GSTs quantitatively,calibration curves were generated by the loading amounts of individual recombinant GST protein vs the relative intensities elicited from the Western *** extensive comparison of the liver mitochondrial GSTs was conducted between normal and db/db diabetic ***'s t test was adopted for the estimation of regression and significant ***:Using GSH affinity/2DE/MALDI TOF/TOF MS,three GSTs,namely,alpha3,mu1 and pi1,were identified;whereas five GSTs,alpha3,mu1,pi1,kappa1 and zeta1,were detected in mouse liver mitochondria using SDS-PAGE/LC ESI MS/MS,of these GSTs,GST kappa1 was reported as a specific mitochondrial *** R 2 values of regression ranged between values of about 0.86 and 0.98,which were acceptable for the *** on the measurement of the GST abundances in liver mitochondria of normal and diabetic mice,the four GSTs,alpha3,kappa1,mu1 and zeta1,were found to be almost comparable between the two sets of animals,whereas,lower GST pi1 was detected in the diabetic mice compared with normal ones,the signal of Western blotting in control and db/db diabetic mice liver mitochondria is 134.61 ± 53.84 vs 99.74 ± 46.2,with P < ***:Our results indicate that GSTs exist widely in mitochondria and its abundances of mitochondrial GSTs might be tissue-dependent and disease-related.

关键词： Glutathione S-transferase Mitochondria,Liver Proteomics Diabetes

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Silencing MYH9 blocks HBx-induced GSK3βubiquitination and degradation to inhibit tumor stemness in hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2361-2372页

作者： Xian Lin Ai-min Li Yong-Hao Li Rong-Cheng Luo Yu-Jiao Zou Yi-Yi Liu Chen Liu ying-ying xie Shi Zuo Zhan Liu Zhen Liu Wei-Yi Fang Cancer Center Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhouGuangdongPeople’s Republic of China510310 Department of Hepatobiliary Surgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhouPeople’s Republic of China550004 Department of Gastroenterology and Clinical Nutrition The First Affiliated Hospital(People’s Hospital of Hunan Province)Hunan Normal UniversityChangshaHunanPeople’s Republic of China410002 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation State Key Laboratory of Respiratory DiseaseSchool of Basic Medical SciencesGuangzhou Medical UniversityAffiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhouGuangdongPeople’s Republic of China510095 Cancer Institute School of Basic Medical ScienceSouthern Medical UniversityGuangzhouGuangdongPeople’s Republic of China510515

MYH9 has dual functions in ***,its role in inducing tumor stemness in hepatocellular carcinoma(HCC)is not yet ***,we found that MYH9 is an effective promoter of tumor stemness that facilitates hepatocellular carcinoma ***,targeting MYH9 remarkably improved the survival of hepatocellular carcinoma-bearing mice and promoted sorafenib sensitivity of hepatocellular carcinoma cells in *** analysis suggested that MYH9 interacted with GSK3βand reduced its protein expression by ubiquitin-mediated degradation,which therefore dysregulated theβ-catenin destruction complex and induced the downstream tumor stemness phenotype,epithelial–mesenchymal transition,and c-Jun signaling in HCC.C-Jun transcriptionally stimulated MYH9 expression and formed an MYH9/GSK3β/β-catenin/c-Jun feedback loop.X protein is a hepatitis B virus(HBV)-encoded key oncogenic protein that promotes HCC ***,we observed that HBV X protein(HBX)interacted with MYH9 and induced its expression by modulating GSK3β/β-catenin/c-Jun *** MYH9 blocked HBX-induced GSK3βubiquitination to activate theβ-catenin destruction complex and suppressed cancer stemness and *** on TCGA database analysis,MYH9 was found to be elevated and conferred poor prognosis for hepatocellular carcinoma *** clinical samples,high MYH9 expression levels predicted poor prognosis of hepatocellular carcinoma *** findings identify the suppression of MYH9 as an alternative approach for the effective eradication of CSC properties to inhibit cancer migration,invasion,growth,and sorafenib resistance in HCC *** study demonstrated that MYH9 is a crucial therapeutic target in HCC.

关键词： GSK3β hepatocellular MYH9

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Observation of topological charge transformations in acoustic vortex using passive periodic systems

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 140-147页

作者： Di-Chao Chen xie Liu Changqing Xu Da-Jian Wu ying Cheng Xiao-Jun Liu School of Physics and Technology Nanjing Normal University Key Laboratory of Modern Acoustics School of Physics Nanjing University

Vortex transmutation utilizes a periodic system, which not only enables the alteration of the topological charge(TC) of unstable input vortices but also facilitates their transformation into stable structures. This approach is crucial for investigating the characteristics of vortices in various wave systems. Here, we achieve acoustic vortex TC transmutation by employing a welldesigned dual-structured plate external system(DPES). The interactions between the acoustic vortex and the finite-order discrete rotational symmetry lead to the transformation of its topological charge when complete rotational symmetry is broken to Nthorder discrete symmetry. Our results experimentally demonstrate the acoustic vortex TC transmutation based on passive artificial structures, enabling numerous applications in particle manipulation and information multiplexing as well as advancing our understanding and control over free-space acoustic vortices.

关键词： acoustic vortex topological charge transformation artificial structure

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东北七鳃鳗肠道应答气单胞菌免疫刺激相关蛋白的鉴定

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中国生物化学与分子生物学报 2016年第11期32卷 1256-1263页

作者：李莹莹解文放朱婷李庆伟辽宁师范大学生命科学学院辽宁师范大学七鳃鳗研究中心辽宁大连116029

动物肠道中寄生的微生物与宿主的营养、免疫及防御功能密切相关。本研究在东北七鳃鳗肠道中分离获得一株优势细菌,并鉴定为气单胞菌属(Aeromonads sp.)。建立了荧光定量PCR快速检测气单胞菌拷贝数的方法,经poly(I∶C)刺激后,气单胞菌数... 详细信息

动物肠道中寄生的微生物与宿主的营养、免疫及防御功能密切相关。本研究在东北七鳃鳗肠道中分离获得一株优势细菌,并鉴定为气单胞菌属(Aeromonads sp.)。建立了荧光定量PCR快速检测气单胞菌拷贝数的方法,经poly(I∶C)刺激后,气单胞菌数量下降1.15倍。因此,该肠道气单胞菌被认为是七鳃鳗肠道适应性免疫系统进化的关键菌群之一。为了进一步分析气单胞菌对东北七鳃鳗肠道适应性免疫影响的分子机制,将分离菌株腹腔注射七鳃鳗,利用双向电泳技术鉴定了七鳃鳗肠道应答气单胞菌免疫刺激的相关蛋白。共鉴定19个差异表达蛋白质,其中12个蛋白质表达上调,5个蛋白质表达下调,1个蛋白质刺激后消失,1个新增蛋白质,并对蛋白质功能进行分类。七鳃鳗肠道应答气单胞菌免疫刺激的差异表达蛋白分别参与了七鳃鳗适应性免疫调控、信号转导及能量代谢等。该研究可拓宽对七鳃鳗免疫研究的途径,为深入探讨适应性免疫系统发育提供理论基础和新的研究思路。

关键词：七鳃鳗肠道气单胞菌肠道蛋白质组肠道免疫

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Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of Gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan xie Jian Yu Kun-Ning Zhang Zhou-Bo Guo Di Wang Zhao-Xian Li Wei-Qi Zhang Yu-ying Tan Li Zhang Wen-Tao Jiang School of Medicine Nankai UniversityTianjin 300192China Tianjin Key Laboratory of Molecular Diagnosis and Treatment of Liver Cancer Tianjin First Center HospitalTianjin 300192China Department of Liver Transplantation Tianjin First Center HospitalTianjin 300192China First Central Clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion Tumor immune microenvironment Apoptosis

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红景天生脉口服液调节免疫功能及抗^(60)Co辐射的实验研究

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时珍国医国药 2003年第11期14卷 664-665页

作者：蔡鹰谢瑛中国人民解放军第454医院江苏南京210002

目的 :观察红景天生脉口服液 (HSY)对小鼠免疫功能的影响及抗 6 0 Co辐射效应。方法 :昆明种小鼠每天每只 3 0 ml· kg- 1,po给药 ,进行碳粒廓清试验 ,抗体溶血素生成试验 ,迟发型皮肤过敏反应实验三项免疫功能测试及用 6 0 Co照射 ,进... 详细信息

目的 :观察红景天生脉口服液 (HSY)对小鼠免疫功能的影响及抗 6 0 Co辐射效应。方法 :昆明种小鼠每天每只 3 0 ml· kg- 1,po给药 ,进行碳粒廓清试验 ,抗体溶血素生成试验 ,迟发型皮肤过敏反应实验三项免疫功能测试及用 6 0 Co照射 ,进行抗辐射测试 ,并与单味红景天制成的口服液 (HY)对照。结果 :HSY及 HY均能提高小鼠巨噬细胞吞噬指数 ,升高小鼠半溶血素值 ,升高小鼠致敏后两跖厚度差 ,升高小鼠 6 0 Co照射后白细胞数 ,提高小鼠存活率。尤以前者为著。结论 :红景天生脉口服液有明显增强小鼠免疫功能的作用及抗辐射效应。

关键词：红景天生脉口服液免疫功能抗^60Co辐射效应

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唾液与血浆中超氧化物歧化酶抑制率的增龄性变化研究

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口腔颌面修复学杂志 2017年第3期18卷 163-167页

作者：徐莹莹解涓朱博王燕一解放军总医院海南分院口腔科硕士生海南572013

目的:检测健康成人唾液与血浆中超氧化物歧化酶(superoxide dismutase,SOD)抑制率,分析两者的相关性以及与年龄的关系。方法:随机选取解放军总医院年龄20-79岁志愿者244例。将受试人群分为青年组(20-44岁),中年组(45-59岁),老年组(60-79... 详细信息

目的:检测健康成人唾液与血浆中超氧化物歧化酶(superoxide dismutase,SOD)抑制率,分析两者的相关性以及与年龄的关系。方法:随机选取解放军总医院年龄20-79岁志愿者244例。将受试人群分为青年组(20-44岁),中年组(45-59岁),老年组(60-79岁);并以性别分组。通过水溶性四唑盐(w ater-soluble tetr azolium salt,WST)法对血浆以及唾液中超氧化物歧化酶抑制率进行检测分析。结果:健康成人血浆整体SOD抑制率为61.27±5.79%;唾液整体SOD抑制率为43.40±12.99%。青年组、中年组、老年组各组血浆以及唾液SOD抑制率差异有统计学意义(P<0.05)。血浆及唾液SOD抑制率与年龄呈负相关(r=-0.61,r=-0.49,P<0.05)。血浆与唾液中SOD抑制率与年龄呈正相关(r=0.43,P<0.05)。但均未发现性别差异。结论:随着年龄的增加唾液和血浆中SOD抑制率减低,且唾液与血液中SOD抑制率正相关。因而通过唾液SOD抑制率的检测可初步评价机体的氧化应激状态。

关键词：超氧化物歧化酶唾液血浆衰老氧化应激

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Multi-layer multi-pass friction rolling additive manufacturing of Al alloy:Toward complex large-scale high-performance components

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 425-438页

作者： Haibin Liu Run Hou Chenghao Wu Ruishan xie Shujun Chen College of Mechanical&Energy Engineering Beijing University of TechnologyBeijing 100124China Chongqing Research Institute of Beijing University of Technology Chongqing 401121China

At present,the emerging solid-phase friction-based additive manufacturing technology,including friction rolling additive man-ufacturing(FRAM),can only manufacture simple single-pass *** this study,multi-layer multi-pass FRAM-deposited alumin-um alloy samples were successfully prepared using a non-shoulder tool *** material flow behavior and microstructure of the over-lapped zone between adjacent layers and passes during multi-layer multi-pass FRAM deposition were studied using the hybrid 6061 and 5052 aluminum *** results showed that a mechanical interlocking structure was formed between the adjacent layers and the adja-cent passes in the overlapped center *** friction and rolling of the tool head led to different degrees of lateral flow and plastic deformation of the materials in the overlapped zone,which made the recrystallization degree in the left and right edge zones of the over-lapped zone the highest,followed by the overlapped center zone and the non-overlapped *** tensile strength of the overlapped zone exceeded 90%of that of the single-pass deposition *** is proved that although there are uneven grooves on the surface of the over-lapping area during multi-layer and multi-pass deposition,they can be filled by the flow of materials during the deposition of the next lay-er,thus ensuring the dense microstructure and excellent mechanical properties of the overlapping *** multi-layer multi-pass FRAM deposition overcomes the limitation of deposition width and lays the foundation for the future deposition of large-scale high-performance components.

关键词： aluminum alloy additive manufacturing solid-state friction stir welding multi-layer multi-pass

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Superhydrophobic and corrosion-resistant siloxane-modified MgAl-LDHs coatings on magnesium alloy prepared under mild conditions

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 450-463页

作者： Wenxi Zhang Zhangzelong Zhuo Dan Xu Liang Wu Zhihui xie Chemical Synthesis and Pollution Control Key Laboratory of Sichuan Province College of Chemistry and Chemical EngineeringChina West Normal UniversityNanchong 637002China College of Materials Science and Engineering/National Engineering Research Center for Magnesium Alloys Chongqing UniversityChongqing 400044China

We have developed a superhydrophobic and corrosion-resistant LDH-W/PFDTMS composite coating on the surface of Mg *** composite comprised a tungstate-intercalated(LDH-W)underlayer that was grown at low temperature(relative to hydrothermal reaction conditions)under atmospheric pressure and an outer polysiloxane layer created from a solution containing perfluorodecyltrimethoxysilane(PFDTMS)using a simple immersion *** successful intercalation of tungstate into the LDH phase and the following formation of the polysiloxane layer were confirmed through X-ray diffraction(XRD),Fourier transform infrared(FTIR)spectroscopy,and X-ray photoelectron spectroscopy(XPS).The corrosion resistance of the LDH-W film,both before and after the PFDTMS modification,was evaluated using electrochemical impedance spectroscopy(EIS),Tafel curves,and immersion *** results showed that Mg coated with LDH-W/PFDTMS exhibited significantly enhanced corrosion protection compared to the unmodified LDHW film,with no apparent signs of corrosion after exposure to 3.5wt%NaCl solution for 15 ***,the LDH-W/PFDTMS coating demonstrated superior superhydrophobicity and self-cleaning properties against water and several common beverages,as confirmed by static contact angle and water-repellency *** results offer valuable insights into preparing superhydrophobic and corrosion-resistant LDH-based composite coatings on Mg alloy surfaces under relatively mild reaction conditions.

关键词： Mg alloy corrosion coating layered double hydroxide

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